Bupropion and Naltrexone in Methamphetamine Use Disorder.

BACKGROUND: The use of naltrexone plus bupropion to treat methamphetamine use disorder has not been well studied. METHODS: We conducted this multisite, double-blind, two-stage, placebo-controlled trial with the use of a sequential parallel comparison design to evaluate the efficacy and safety of extended-release injectable naltrexone (380 mg every 3 weeks) plus oral extended-release bupropion (450 mg per day) in adults with moderate or severe methamphetamine use disorder. In the first stage of the trial, participants were randomly assigned in a 0.26:0.74 ratio to receive naltrexone-bupropion or matching injectable and oral placebo for 6 weeks. Those in the placebo group who did not have a response in stage 1 underwent rerandomization in stage 2 and were assigned in a 1:1 ratio to receive naltrexone-bupropion or placebo for an additional 6 weeks. Urine samples were obtained from participants twice weekly. The primary outcome was a response, defined as at least three methamphetamine-negative urine samples out of four samples obtained at the end of stage 1 or stage 2, and the weighted average of the responses in the two stages is reported. The treatment effect was defined as the between-group difference in the overall weighted responses. RESULTS: A total of 403 participants were enrolled in stage 1, and 225 in stage 2. In the first stage, 18 of 109 participants (16.5%) in the naltrexone-bupropion group and 10 of 294 (3.4%) in the placebo group had a response. In the second stage, 13 of 114 (11.4%) in the naltrexone-bupropion group and 2 of 111 (1.8%) in the placebo group had a response. The weighted average response across the two stages was 13.6% with naltrexone-bupropion and 2.5% with placebo, for an overall treatment effect of 11.1 percentage points (Wald z-test statistic, 4.53; P<0.001). Adverse events with naltrexone-bupropion included gastrointestinal disorders, tremor, malaise, hyperhidrosis, and anorexia. Serious adverse events occurred in 8 of 223 participants (3.6%) who received naltrexone-bupropion during the trial. CONCLUSIONS: Among adults with methamphetamine use disorder, the response over a period of 12 weeks among participants who received extended-release injectable naltrexone plus oral extended-release bupropion was low but was higher than that among participants who received placebo. (Funded by the National Institute on Drug Abuse and others; ADAPT-2 ClinicalTrials.gov number, NCT03078075.).

Overdose from Unintentional Fentanyl Use when Intending to Use a Non-opioid Substance: An Analysis of Medically Attended Opioid Overdose Events.

Fentanyl-mixed and substituted heroin is well-documented, but less is known about unintentional fentanyl use among people using stimulants. To determine the prevalence of and racial and ethnic disparities in unintentional fentanyl use among people experiencing a medically attended opioid overdose, we reviewed 448 suspected non-fatal overdose cases attended by a community paramedic overdose response team in San Francisco from June to September 2022. We applied a case definition for opioid overdose to paramedic records and abstracted data on intended substance use prior to overdose. Among events meeting case criteria with data on intended substance use, intentional opioid use was reported by 57.3%, 98.0% of whom intended to use fentanyl. No intentional opioid use was reported by 42.7%, with most intending to use stimulants (72.6%), including methamphetamine and cocaine. No intentional opioid use was reported by 58.5% of Black, 52.4% of Latinx, and 28.8% of White individuals (p = 0.021), and by 57.6% of women and 39.5% of men (p = 0.061). These findings suggest that unintentional fentanyl use among people without opioid tolerance may cause a significant proportion of opioid overdoses in San Francisco. While intentional fentanyl use might be underreported, the magnitude of self-reported unintentional use merits further investigation to confirm this phenomenon, explore mechanisms of use and disparities by race and ethnicity, and deploy targeted overdose prevention interventions.

"They made me feel like I mattered": a qualitative study of how mobile crisis teams can support people experiencing homelessness.

BACKGROUND: Mobile crisis teams (MCTs) can be important alternatives to emergency medical services or law enforcement for low-acuity 911 calls. MCTs address crises by de-escalating non-violent situations related to mental health or substance use disorders and concurrent social needs, which are common among people experiencing homelessness (PEH). We sought to explore how an MCT in one city served the needs and supported the long- and short-term goals of PEH who had recently received MCT services. METHODS: We conducted 20 semi-structured interviews with service recipients of the Street Crisis Response Team, a new 911-dispatched MCT implemented in San Francisco in November 2020. In the weeks after their encounter, we interviewed respondents about their overall MCT experience and comparisons to similar services, including perceived facilitators and barriers to the respondent's self-defined life goals. We analyzed interview transcripts with thematic analysis to capture salient themes emerging from the text and organized within a social-ecological model. RESULTS: Nearly all respondents preferred the MCT model over traditional first responders, highlighting the team's person-centered approach. Respondents described the MCT model as effectively addressing their most immediate needs (e.g., food), short-term relief from the demands of homelessness, acute mental health or substance use symptoms, and immediate emotional support. However, systemwide resource constraints limited the ability of the team to effectively address longer-term factors that drive crises, such as solutions to inadequate quality and capacity of current housing and healthcare systems and social services navigation. CONCLUSIONS: In this study, respondents perceived this MCT model as a desirable alternative to law enforcement and other first responders while satisfying immediate survival needs. To improve MCT's effectiveness for PEH, these teams could collaborate with follow-up providers capable of linking clients to resources and services that can meet their long-term needs. However, these teams may not be able to meaningfully impact the longstanding and complex issues that precipitate crises among PEH in the absence of structural changes to upstream drivers of homelessness and fragmentation of care systems.

Withdrawal during outpatient low dose buprenorphine initiation in people who use fentanyl: a retrospective cohort study.

BACKGROUND: Buprenorphine is an effective treatment for opioid use disorder (OUD); however, buprenorphine initiation can be complicated by withdrawal symptoms including precipitated withdrawal. There has been increasing interest in using low dose initiation (LDI) strategies to reduce this withdrawal risk. As there are limited data on withdrawal symptoms during LDI, we characterize withdrawal symptoms in people with daily fentanyl use who underwent initiation using these strategies as outpatients. METHODS: We conducted a retrospective chart review of patients with OUD using daily fentanyl who were prescribed 7-day or 4-day LDI at 2 substance use disorder treatment clinics in San Francisco. Two addiction medicine experts assessed extracted chart documentation for withdrawal severity and precipitated withdrawal, defined as acute worsening of withdrawal symptoms immediately after taking buprenorphine. A third expert adjudicated disagreements. Data were analyzed using descriptive statistics. RESULTS: There were 175 initiations in 126 patients. The mean age was 37 (SD 10 years). 71% were men, 26% women, and 2% non-binary. 21% identified as Black, 16% Latine, and 52% white. 60% were unstably housed and 75% had Medicaid insurance. Substance co-use included 74% who used amphetamines, 29% cocaine, 22% benzodiazepines, and 19% alcohol. Follow up was available for 118 (67%) initiations. There was deviation from protocol instructions in 22% of these initiations with follow up. 31% had any withdrawal, including 21% with mild symptoms, 8% moderate and 2% severe. Precipitated withdrawal occurred in 10 cases, or 8% of initiations with follow up. Of these, 7 had deviation from protocol instructions; thus, there were 3 cases with follow up (3%) in which precipitated withdrawal occurred without protocol deviation. CONCLUSIONS: Withdrawal was relatively common in our cohort but was mostly mild, and precipitated withdrawal was rare. Deviation from instructions, structural barriers, and varying fentanyl use characteristics may contribute to withdrawal. Clinicians should counsel patients who use fentanyl that mild withdrawal symptoms are likely during LDI, and there is still a low risk for precipitated withdrawal. Future studies should compare withdrawal across initiation types, seek ways to support patients in initiating buprenorphine, and qualitatively elicit patients' withdrawal experiences.

Cocaine Use is Associated With Increased LVMI in Unstably Housed Women With Polysubstance Use.

BACKGROUND: While substance use is known to influence cardiovascular health, most prior studies only consider one substance at a time. We examined associations between the concurrent use of multiple substances and left ventricular mass index (LVMI) in unhoused and unstably housed women. METHODS: Between 2016 and 2019, we conducted a cohort study of unstably housed women in which measurements included an interview, serum/urine collection, vital sign assessment, and a single transthoracic echocardiogram at baseline. We evaluated independent associations between 39 separate substances confirmed through toxicology and echocardiography-confirmed LVMI. RESULTS: The study included 194 participants with a median age of 53.5 years and a high proportion of women of color (72.6%). Toxicology-confirmed substance use included: 69.1% nicotine, 56.2% cocaine, 28.9% methamphetamines, 28.9% alcohol, 23.2% opioid analgesics, and 9.8% opioids with catecholaminergic effects. In adjusted analysis, cocaine was independently associated with higher LVMI (Adjusted linear effect: 18%; 95% CI 9.9, 26.6). Associations with other substances did not reach levels of significance and did not significantly interact with cocaine. CONCLUSION: In a population of vulnerable women where the use of multiple substances is common, cocaine stands out as having particularly detrimental influences on cardiac structure. Blood pressure did not attenuate the association appreciably, suggesting direct effects of cocaine on LVMI. Routinely evaluating stimulant use as a chronic risk factor during risk assessment and preventive clinical care planning may reduce end organ damage, particularly in highly vulnerable women.

Comparative 1-Year Outcomes of Invasive Staphylococcus aureus Infections Among Persons With and Without Drug Use: An Observational Cohort Study.

BACKGROUND: Persons who use drugs (PWUD) face substantial risk of Staphylococcus aureus infections. Limited data exist describing clinical and substance use characteristics of PWUD with invasive S. aureus infections or comparing treatment and mortality outcomes in PWUD vs non-PWUD. These are needed to inform optimal care for this marginalized population. METHODS: We identified adults hospitalized from 2013 to 2018 at 2 medical centers in San Francisco with S. aureus bacteremia or International Classification of Diseases-coded diagnoses of endocarditis, epidural abscess, or vertebral osteomyelitis with compatible culture. In addition to demographic and clinical characteristic comparison, we constructed multivariate Cox proportional hazards models for 1-year infection-related readmission and mortality, adjusted for age, race/ethnicity, housing, comorbidities, and methicillin-resistant S. aureus (MRSA). RESULTS: Of 963 hospitalizations for S. aureus infections in 946 patients, 372 of 963 (39%) occurred in PWUD. Among PWUD, heroin (198/372 [53%]) and methamphetamine use (185/372 [50%]) were common. Among 214 individuals using opioids, 98 of 214 (46%) did not receive methadone or buprenorphine. PWUD had lower antibiotic completion than non-PWUD (70% vs 87%; P < .001). While drug use was not associated with increased mortality, 1-year readmission for ongoing or recurrent infection was double in PWUD vs non-PWUD (28% vs 14%; adjusted hazard ratio [aHR], 2.0 [95% confidence interval {CI}: 1.3-2.9]). MRSA was independently associated with 1-year readmission for infection (aHR, 1.5 [95% CI: 1.1-2.2]). CONCLUSIONS: Compared to non-PWUD, PWUD with invasive S. aureus infections had lower rates of antibiotic completion and twice the risk of infection persistence/recurrence at 1 year. Among PWUD, both opioid and stimulant use were common. Models for combined treatment of substance use disorders and infections, particularly MRSA, are needed.

Evaluating the Effects of Opioid Prescribing Policies on Patient Outcomes in a Safety-net Primary Care Clinic.

BACKGROUND: After decades of liberal opioid prescribing, multiple efforts have been made to reduce reliance upon opioids in clinical care. Little is known about the effects of opioid prescribing policies on outcomes beyond opioid prescribing. OBJECTIVE: To evaluate the combined effects of multiple opioid prescribing policies implemented in a safety-net primary care clinic in San Francisco, CA, in 2013-2014. DESIGN: Retrospective cohort study and conditional difference-in-differences analysis of nonrandomized clinic-level policies. PATIENTS: 273 patients prescribed opioids for chronic non-cancer pain in 2013 at either the treated (n=151) or control clinic (n=122) recruited and interviewed in 2017-2018. INTERVENTIONS: Policies establishing standard protocols for dispensing opioid refills and conducting urine toxicology testing, and a new committee facilitating opioid treatment decisions for complex patient cases. MAIN MEASURES: Opioid prescription (active prescription, mean dose in morphine milligram equivalents [MME]) from electronic medical charts, and heroin and opioid analgesics not prescribed to the patient (any use, use frequency) from a retrospective interview. KEY RESULTS: The interventions were associated with a reduction in mean prescribed opioid dose in the first three post-policy years (year 1 conditional difference-in-differences estimate: -52.0 MME [95% confidence interval: -109.9, -10.6]; year 2: -106.2 MME [-195.0, -34.6]; year 3: -98.6 MME [-198.7, -23.9]; year 4: -72.6 MME [-160.4, 3.6]). Estimates suggest a possible positive association between the interventions and non-prescribed opioid analgesic use (year 3: 5.2 absolute percentage points [-0.1, 11.2]) and use frequency (year 3: 0.21 ordinal frequency scale points [0.00, 0.47]) in the third post-policy year. CONCLUSIONS: Clinic-level opioid prescribing policies were associated with reduced dose, although the control clinic achieved similar reductions by the fourth post-policy year, and the policies may have been associated with increased non-prescribed opioid analgesic use. Clinicians should balance the urgency to reduce opioid prescribing with potential harms from rapid change.

A Chronic Condition Disguised as an Acute Event: the Case for Re-thinking Stimulant Overdose Death.

Recent reports indicate that stimulant-related deaths are increasing dramatically. People who die from acute stimulant toxicity have high rates of pre-existing cardiovascular disease (CVD), much of which is undiagnosed. Moreover, people who use stimulants with CVD often remain asymptomatic until presenting to an emergency department with an acute event. Prior research shows that symptoms of stimulant toxicity may occur on a regular basis, and that people who die from stimulant toxicity are older than those who die of opioid toxicity. Taken collectively, the existing evidence suggests that death from acute stimulant toxicity is often an outcome of long-term, cumulative exposure leading to cardiovascular dysfunction rather than acute intoxication. Strategies tailored to the distinct etiology of stimulant overdose are needed. We propose a three-part approach including (1) implementing stimulant use interventions that promote not only abstinence, but also use reduction, (2) treating ongoing stimulant use as a chronic cardiovascular condition, and (3) making stimulant toxicity interventions relevant to the populations most affected, which includes people outside of the traditional health-care system. In short, to reduce stimulant-related fatality, we need to transform our approach in ways that are tailored to address its natural history.

Correlates of high phosphatidylethanol (PEth) levels and their concordance with self-reported heavy alcohol consumption among men who have sex with men who binge drink alcohol.

BACKGROUND: Heavy alcohol use, including binge drinking, is associated with high morbidity and mortality among men who have sex with men (MSM). Self-reported alcohol measures may lead to inaccurate estimates due to recall and social desirability biases. Objective alcohol biomarkers like phosphatidylethanol (PEth) can be used to corroborate self-report and could help to inform treatment approaches and research strategies for alcohol using MSM. METHODS: From 2015 to 2020, alcohol using MSM ≥18 years were enrolled in a randomized controlled trial evaluating the efficacy of naltrexone in reducing binge drinking. Using this trial's baseline data, we applied multivariable logistic regression to identify the correlates of high PEth levels (i.e., ≥87 ng/ml) and concordance between PEth levels and self-reported heavy drinking. RESULTS: Of 118 MSM, 64% had PEth levels ≥87 ng/ml and 72% had PEth levels that were concordant with self-reported heavy alcohol use. Factors significantly associated in separate models with elevated PEth levels were income ≥$60,000 (adjusted odds ratio [aOR] = 4.09; 95% CI = 1.13 to 14.82), being employed (aOR = 4.04; 95% CI = 1.45 to 11.32), episodic cannabis use (aOR = 4.63; 95% CI = 1.27 to 16.92), and any alcohol/substance use prior to or during anal intercourse (aOR = 2.52; 95% CI = 1.08 to 5.90). Living with HIV was associated with significantly lower odds of elevated PEth levels (aOR = 0.23; 95% CI = 0.09 to 0.61). Factors associated with significantly higher concordance between PEth levels and self-reported heavy alcohol use included at least weekly use of poppers (aOR = 6.41; 95% CI = 1.27 to 32.28) and polysubstance use (aOR = 2.53; 95% CI = 1.02 to 6.27). Living with HIV was associated with lower odds of concordance (aOR = 0.36; 95% CI = 0.14 to 0.97). CONCLUSIONS: PEth may enhance the detection of heavy drinking among MSM, including the identification of subpopulations that may benefit from targeted alcohol reduction interventions. However, PEth values for MSM living with HIV showed modest concordance with self-reported alcohol use and may need to be supplemented with additional biomarkers or evaluated against a different cutoff.

Impact of multiple substance use on circulating ST2, a biomarker of adverse cardiac remodelling, in women.

CONTEXT: Cardiovascular disease (CVD) and heart failure (HF) are major causes of mortality in low-income populations and differ by sex. Risk assessment that incorporates cardiac biomarkers is common. However, research evaluating the utility of biomarkers rarely includes controlled substances, which may influence biomarker levels and thus influence CVD risk assessment. MATERIALS AND METHODS: We identified the effects of multiple substances on soluble "suppression of tumorigenicity 2" (sST2), a biomarker of adverse cardiac remodelling, in 245 low-income women. Adjusting for CVD risk factors, we examined associations between substance use and sST2 over six monthly visits. RESULTS: Median age was 53 years and 74% of participants were ethnic minority women. An sST2 level > 35 ng/mL (suggesting cardiac remodelling) during ≥1 study visit was observed in 44% of participants. In adjusted analysis, higher sST2 levels were significantly and positively associated with the presence of cocaine (Adjusted Linear Effect [ALE]:1.10; 95% CI:1.03-1.19), alcohol (ALE:1.10; 95% CI:1.04-1.17), heroin (ALE:1.25; 95% CI:1.10-1.43), and the interaction between heroin and fentanyl use. CONCLUSION: Results suggest that the use of multiple substances influences the level of sST2, a biomarker often used to evaluate cardiovascular risk. Incorporating substance use alongside cardiac biomarkers may improve CVD risk assessment in vulnerable women.

Engagement in HIV care and viral suppression following changes in long-term opioid therapy for treatment for chronic pain.

Chronic pain is common among persons living with HIV and changes in opioid prescribing practices may complicate HIV care management. Using medical record data from a retrospective cohort study conducted January 1, 2012 to June 30, 2019 for 300 publicly insured HIV-positive primary care patients prescribed opioids for chronic non-cancer pain in San Francisco, we examined associations between opioid dose changes and both time to disengagement from HIV care and experiencing virologic failure using logistic regression. Discontinuation of prescribed opioids was associated with increased odds of disengagement in care at 3, 6, and 9 months after discontinuation. There were no associations with virologic failure. Providers and policy makers must weigh impacts on HIV care when implementing necessary changes in opioid prescribing.

Evidence of Pre-mortem Opioid Use among Fentanyl Overdose Decedents in a Safety Net Healthcare System.

The rapid increase in fentanyl overdose deaths, particularly those also attributed to stimulants, has led to concerns about unintentional fentanyl exposure. Utilizing vital and medical record data, we identified overdose decedents from 2018 to 2021 in San Francisco who received care in the safety net system in the 3 years preceding death. Among 506 decedents, medical record evidence of pre-mortem opioid use was present for 48% of stimulant-only, 56% of stimulant-fentanyl, 65% of fentanyl-only, and 82% of non-fentanyl opioid decedents (p<0.001). Among stimulant-fentanyl decedents, an increase in 10 years of age (adjusted odds ratio (aOR) 0.74 [95% CI:0.59-0.94]) and race other than White or Black (aOR 0.36 [95% CI:0.15-0.87]) had lower odds of evidence of pre-mortem opioid use. While not conclusive, these findings raise the possibility that a significant proportion of fentanyl overdose decedents in San Francisco may have not intended to consume an opioid on the occasion of their death.

Stimulant use for self-management of pain among safety-net patients with chronic non-cancer pain.

BACKGROUND: Chronic pain affects one-fifth of US adults. Reductions in opioid prescribing have been associated with increased non-prescription opioid use and, chronologically, increased stimulant (methamphetamine and cocaine) use. While non-prescription opioid use is commonly attributed to pain self-management, the role of stimulants in managing pain is unclear. METHODS: We analyzed baseline data from a longitudinal study of patients with chronic non-cancer pain in an urban safety-net healthcare system who had been prescribed an opioid for ≥3 of the last 12 months, and had a history of non-prescription opioid, cocaine, or amphetamine use (N = 300). We estimated the prevalence and identified correlates of stimulant use to treat pain among a subgroup of patients who reported past-year stimulant use (N = 105). Data sources included computer-assisted questionnaire (demographics, substance use, pain), clinical exam and procedures (pain, pain tolerance), and chart abstraction (opioid prescriptions). We conducted bivariate analyses to assess associations between demographics, pain characteristics, non-opioid therapies, substance use, opioid prescriptions, and self-reported symptoms, with reporting using stimulants to treat pain. Demographic variables and those with significant bivariate associations were included in a multivariable logistic regression model. RESULTS: Fifty-two percent of participants with past-year stimulant use reported using stimulants in the past year to treat pain. Participants who used stimulants for pain reported slightly higher average pain in the past 3 months (median of 8 (IQR: 6-8) vs 7 (7-9) out of 10, p = 0.049). In the multivariable analysis, female gender (AOR= 3.20, 95% CI: 1.06-9.63, p = 0.039) and higher score on the Douleur Neuropathique 4 neuropathic pain questionnaire (AOR = 1.34, 95% CI: 1.05-1.70, p = 0.017) were associated with past-year stimulant use to treat pain. CONCLUSION: Stimulants may be used for pain self-management, particularly for neuropathic pain and among women. Our findings suggest an underexplored motivation for stimulant use in an era of reduced access to prescribed opioids.

Emergency department visits and trends related to cocaine, psychostimulants, and opioids in the United States, 2008-2018.

BACKGROUND: Drug-related emergency department (ED) visits are escalating, especially for stimulant use (i.e., cocaine and psychostimulants such as methamphetamine). We sought to characterize rates, presentation, and management of ED visits related to cocaine and psychostimulant use, compared to opioid use, in the United States (US). METHODS: We used 2008-2018 National Hospital Ambulatory Medical Care Survey data to identify a nationally representative sample of ED visits related to cocaine and psychostimulant use, with opioids as the comparator. To make visits mutually exclusive for analysis, we excluded visits related to 2 or more of the three possible drug categories. We estimated annual rate trends using unadjusted Poisson regression; described demographics, presenting concerns, and management; and determined associations between drug-type and presenting concerns (categorized as psychiatric, neurologic, cardiopulmonary, and drug toxicity/withdrawal) using logistic regression, adjusting for age, sex, race/ethnicity, and homelessness. RESULTS: Cocaine-related ED visits did not significantly increase, while psychostimulant-related ED visits increased from 2008 to 2018 (2.2 visits per 10,000 population to 12.9 visits per 10,000 population; p < 0.001). Cocaine-related ED visits had higher usage of cardiac testing, while psychostimulant-related ED visits had higher usage of chemical restraints than opioid-related ED visits. Cocaine- and psychostimulant-related ED visits had greater odds of presenting with cardiopulmonary concerns (cocaine adjusted odds ratio [aOR] 2.95, 95% CI 1.70-5.13; psychostimulant aOR 2.46, 95% CI 1.42-4.26), while psychostimulant-related visits had greater odds of presenting with psychiatric concerns (aOR 2.69, 95% CI 1.83-3.95) and lower odds of presenting with drug toxicity/withdrawal concerns (aOR 0.47, 95%CI 0.30-0.73) compared to opioid-related ED visits. CONCLUSION: Presentations for stimulant-related ED visits differ from opioid-related ED visits: compared to opioids, ED presentations related to cocaine and psychostimulants are less often identified as related to drug toxicity/withdrawal and more often require interventions to address acute cardiopulmonary and psychiatric complications.

Addressing overdose risk among unstably housed women in San Francisco, California: an examination of potential fentanyl contamination of multiple substances.

BACKGROUND: Numerous reports have led to concerns that fentanyl is added to many street drugs as an adulterant, including to stimulants like cocaine and methamphetamine, and could increase risks for negative health outcomes. METHODS: We collected information regarding recent substance use through self-report and urine toxicology (confirmed with mass spectrometry) once a month for up to 6 monthly study visits from a probability sample of 245 women in San Francisco with a history of housing instability (2016-2019). We compared the presence of fentanyl metabolites with (1) the presence of metabolites for other substances and (2) self-reported past week substance use. RESULTS: Out of 1050 study visits, fentanyl metabolites were detected 35 times (i.e., at 3% of all study visits and among 19/245, or 8% of all women). In most but not all (91%, or 32/35) of these detected cases, heroin or opioid medication use was self-reported. Among women who reported cocaine or methamphetamine use, but did not use heroin or opioid medication, fentanyl was detected in only 1 of 349 cases (0.3%). In adjusted logistic regression, the presence of fentanyl metabolites was independently associated with (1) presence of opiate, heroin, and benzodiazepine metabolites, and (2) self-reported past week use of heroin and opioid medications. Fentanyl metabolite detection was not independently associated with cocaine or methamphetamine use. CONCLUSIONS: The presence of fentanyl metabolites in this population was almost entirely among women who also reported using heroin or opioid pills. These data do not support the hypothesis that fentanyl is being routinely added to stimulants as an adulterant on a large scale in this region.

Community-Based Response to Fentanyl Overdose Outbreak, San Francisco, 2015.

This report documents a successful intervention by a community-based naloxone distribution program in San Francisco. The program and its partner organizations, working with participants who use drugs, first identified the appearance of illicitly made fentanyl and increased outreach and naloxone distribution. Distribution of naloxone and reported use of naloxone to reverse opioid-involved overdoses increased significantly while the number of opioid-involved and fentanyl-involved overdose deaths did not. Community-based programs that provide training and naloxone to people who use drugs can serve as an early warning system for overdose risk and adaptively respond to the rapidly changing overdose risk environment.

Impacts of an opioid overdose prevention intervention delivered subsequent to acute care.

BACKGROUND: Opioid overdose is a major and increasing cause of injury and death. There is an urgent need for interventions to reduce overdose events among high-risk persons. METHODS: Adults at elevated risk for opioid overdose involving heroin or pharmaceutical opioids who had been cared for in an emergency department (ED) were randomised to overdose education combined with a brief behavioural intervention and take-home naloxone or usual care. Outcomes included: (1) time to first opioid overdose-related event resulting in medical attention or death using competing risks survival analysis; and (2) ED visit and hospitalisation rates, using negative binomial regression and adjusting for time at risk. RESULTS: During the follow-up period, 24% of the 241 participants had at least one overdose event, 85% had one or more ED visits and 55% had at least one hospitalisation, with no significant differences between intervention and comparison groups. The instantaneous risk of an overdose event was not significantly lower for the intervention group (sub-HR: 0.83; 95% CI 0.49 to 1.40). DISCUSSION: These null findings may be due in part to the severity of the population in terms of housing insecurity (70% impermanently housed), drug use, unemployment and acute healthcare issues. Given the high overdose and healthcare utilisation rates, more intensive interventions, such as direct referral and provision of housing and opioid agonist treatment medications, may be necessary to have a substantial impact on opioid overdoses for this high-acuity population in acute care settings. TRIAL REGISTRATION NUMBER: NCT0178830; Results.

Perceived Causes of Personal versus Witnessed Overdoses among People who Inject Opioids.

Background: Studies show that people who inject drugs (PWID) underestimate their overdose risk. We sought to explore this phenomenon by comparing how PWID perceive causes of personal overdoses compared to witnessed overdoses. Methods: We analyzed 40 interviews from participants enrolled in a randomized-controlled behavioral intervention to reduce overdose among at-risk PWID in San Francisco from 2014 to 2016. Subjects were current illicit opioid injectors with opioid use disorder, had received take-home naloxone, and had overdosed within five years. Interviews were audio-recorded and transcribed verbatim. Using thematic content analysis, three analysts coded the interviews and measured interrater reliability. The analysts developed a codebook of a priori and inductively generated codes, and applied it to all interviews. Coding discrepancies were discussed. Results: We used two theoretical frameworks - actor observer bias (AOB) and intragroup stigma - to analyze participants' descriptions of personal and witnessed overdoses. AOB suggests individuals may assign responsibility of their actions to external factors, while assigning responsibility for others' actions to internal mechanisms. Intragroup stigma describes the process whereby people perpetuate stigma within their own group. Related to these concepts, two principal themes were used to describe personal overdose: (1) drug volatility and (2) ascribing blame to others, and witnessed overdoses: (1) greed and (2) inexperience/foolishness. Conclusion/Importance: The differences in perceived causes of personal versus witnessed overdose align with AOB and intragroup stigma. Understanding how these theories shape overdose experiences may improve behavioral interventions by introducing peer based supports and encouraging PWIDs to employ evidence-based safety precautions when using opioids.

Acceptability and feasibility of naloxone prescribing in primary care settings: A systematic review.

Naloxone access through established healthcare settings is critical to responding to the opioid crisis. We conducted a systematic review to assess the acceptability and feasibility of prescribing naloxone to patients in primary care. We queried PubMed, EmBase and CINAHL for US-based, peer-reviewed, full-length, original articles relating to acceptability or feasibility of prescribing naloxone in primary care. Searches yielded 270 unduplicated articles; one analyst reviewed all titles and abstracts. Two analysts independently reviewed eligible articles for study design, study outcome, and acceptability and/or feasibility. Analyses were compared and a third reviewer consulted if discrepancies emerged. Seventeen articles were included. Providers' willingness to prescribe naloxone appeared to increase over time. Most studies provided prescribers in-person naloxone trainings, including how to write a prescription and indications for prescribing. Most studies implemented universal prescribing, whereby anyone prescribed long-term opioids or otherwise at risk for overdose was eligible for naloxone. Patient education was largely provided by prescribers and most studies provided take-home educational materials. Providers reported concerns around naloxone prescribing including lack of knowledge around prescribing and educating patients. Providers also reported benefits such as improving difficult conversations around opioids and resetting the culture around opioids and overdose. Current literature supports the acceptability and feasibility of naloxone prescribing in primary care. Provision of naloxone through primary care may help normalize such medication safety interventions, support larger opioid stewardship efforts, and expand access to patients not served by a community distribution program.