Search

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.

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.

BACKGROUND: Significant disparities in substance use severity and treatment persist among women who use drugs compared to men. Thus, we explored how identifying as a woman was related to drug use and treatment experiences. METHODS: The study recruited participants for a qualitative interview study in Boston and San Francisco from January-November 2020. Self-identified women, age ≥ 18 years, with nonprescribed opioid use in the past 14 days were eligible for inclusion. The study team developed deductive codes based on intersectionality theory and inductive codes generated from transcript review, and identified themes using grounded content analysis. RESULTS: The study enrolled thirty-six participants. The median age was 46; 58 % were White, 16 % were Black, 14 % were Hispanic, and 39 % were unstably housed. Other drug use was common with 81 % reporting benzodiazepine, 50 % cocaine, and 31 % meth/amphetamine use respectively. We found that gender (i.e., identifying as a woman) intersected with drug use and sex work practices and exacerbated experiences of marginalization. Violence was ubiquitous in drug use environments. Some women reported experiences of gender-based violence in substance use service settings that perpetuated cycles of trauma and reinforced barriers to care. Substance use services that were women-led, safe, and responsive to womens needs were valued and sought after. CONCLUSION: Women reported a cycle of trauma and drug use exacerbated by oppression in substance use services settings. In addition to increasing access to gender-responsive care, our study highlights the need for greater research and examination of practices within substance use service settings that may be contributing to gender-based violence.

Methamphetamine Toxicities and Clinical ManagementMethamphetamine increases the release and blocks the uptake of norepinephrine, serotonin, and dopamine. This article reviews the morbidity and mortality associated with methamphetamine use and discusses prevention and treatment strategies.

BackgroundWhile 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.MethodsBetween 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.ResultsThe 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.ConclusionIn 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.

BackgroundMethamphetamine use disorder (MethUD) disproportionately affects men who have sex exclusively with men or with men and women (collectively MSM/W), compared to men who have sex with women (MSW). This study is the first MethUD medication trial to compare treatment effect for these groups, hypothesizing that extended-release injectable naltrexone 380mg every 3 weeks plus oral extended-release bupropion 450mg daily would be less effective for MSM/W than MSW.MethodsData come from men (N = 246) in a multi-site, double-blind, randomized, placebo-controlled trial with sequential parallel comparison design. In Stage 1 (6-weeks), participants were randomized to active treatment or placebo. In Stage 2 (6-weeks), Stage 1 placebo non-responders were rerandomized. Treatment response was ≥3 methamphetamine-negative urine samples, out of four obtained at the end of Stages 1 and 2. Treatment effect was the active-versus-placebo between-group difference in the weighted average Stages 1 and 2 responses.ResultsMSM/W (n = 151) were more likely than MSW (n = 95) to be Hispanic, college-educated, and living with HIV. Adjusting for demographics, among MSM/W, response rates were 13.95 % (active treatment) and 2.78 % (placebo) in Stage 1; 23.26 % (active treatment) and 4.26 % (placebo) in Stage 2. Among MSW, response rates were 7.69 % (active treatment) and 5.80 % (placebo) in Stage 1; 3.57 % (active treatment) and 0 % (placebo) in Stage 2. Treatment effect was significantly larger for MSM/W (h = 0.1479) than MSW (h = 0.0227) (p = 0.04).ConclusionsFindings suggest efficacy of extended-release naltrexone plus bupropion for MSM/W, a population heavily burdened by MethUD. While a secondary outcome, this intriguing finding merits testing in prospective trials.

BackgroundSubstance use increases risk of cardiovascular events, particularly among women with additional risk factors like housing instability. While multiple substance use is common among unstably housed individuals, relationships between multiple substance use and cardiovascular risk factors like blood pressure are not well characterized.MethodsWe conducted a cohort study between 2016 and 2019 to examine associations between multiple substance use and blood pressure in women experiencing homelessness and unstable housing. Participants completed six monthly visits including vital sign assessment, interview, and blood draw to assess toxicology-confirmed substance use (e.g., cocaine, alcohol, opioids) and cardiovascular health. We used linear mixed models to evaluate the outcomes of systolic and diastolic blood pressure (SBP; DBP).ResultsMean age was 51.6 years; 74 % were women of color. Prevalence of any substance use was 85 %; 63 % of participants used at least two substances at baseline. Adjusting for race, body mass index and cholesterol, cocaine was the only substance significantly associated with SBP (4.71 mmHg higher; 95 % CI 1.68, 7.74) and DBP (2.83 mmHg higher; 95 % CI 0.72, 4.94). Further analysis found no differences in SBP or DBP between those with concurrent use of other stimulants, depressants, or both with cocaine, compared to those who used cocaine only.ConclusionsCocaine was the only substance associated with higher SBP and DBP, even after accounting for simultaneous use of other substances. Along with interventions to address cocaine use, stimulant use screening during cardiovascular risk assessment and intensive blood pressure management may improve cardiovascular outcomes among women experiencing housing instability.

Mobile crisis services for people experiencing distress related to mental health or substance use are expanding rapidly across the US, yet there is little evidence to support these specific models of care. These new programs present a unique opportunity to expand the literature by utilizing implementation science methods to inform the future design of crisis systems. This mixed methods study will examine the effectiveness and acceptability of the Street Crisis Response Team (SCRT), a new 911-dispatched multidisciplinary mobile crisis intervention piloted in San Francisco, California. First, using quantitative data from electronic health records, we will conduct an interrupted time series analysis to quantitatively examine the impacts of the SCRT on people experiencing homelessness who utilized public behavioral health crisis services in San Francisco between November 2019 and August 2022, across four main outcomes within 30 days of the crisis episode: routine care utilization, crisis care reutilization, assessment for housing services, and jail entry. Second, to understand its impact on health equity, we will analyze racial and ethnic disparities in these outcomes prior to and after implementation of the SCRT. For the qualitative component, we will conduct semi-structured interviews with recipients of the SCRTs services to understand their experiences of the intervention and to identify how the SCRT influenced their health-related trajectories after the crisis encounter. Once complete, the quantitative and qualitative findings will be further analyzed in tandem to assist with more nuanced understanding of the effectiveness of the SCRT program. This evaluation of a novel mobile crisis response program will advance the field, while also providing a model for how real-world program implementation can be achieved in crisis service settings.

Abstract: Background: Amidst interrelated problems of increasing infections related to drug use and overdose deaths, contingency management (CM) is an underutilized substance use disorder treatment that leverages incentives for objective behavior change. CM implementation outside of drug treatment settings is limited, despite its regard as gold-standard treatment for stimulant use disorder and potential use to support infection treatment completion. Objective: to describe feasibility and preliminary effectiveness of a novel CM program incentivizing reduced drug use and antibiotic adherence in the acute care setting. Methods: We conducted a pilot of twice weekly CM in an urban public hospital and its attached skilled nursing facility with escalating opportunities to earn incentives from a fishbowl based on 1) antibiotic adherence and/or 2) absence of stimulants or opioids on urine drug testing. Eligible participants were people with stimulant and/or opioid use disorders hospitalized for at least 2 weeks of infection treatment. We measured feasibility via visits attempted/completed and cost of gift cards dispensed. We evaluated effectiveness via antibiotic completion, discharge type, and participant perception of intervention effectiveness collected via structured survey. Results: Between March-April 2022, n=9 participants were referred to IMPACT, and n=7 were enrolled. Most participants (5/7) required antibiotics for osteomyelitis, and most had stimulant use disorder (methamphetamine, 5/7) and opioid use disorder (fentanyl, 5/7). In 4 of 7 instances, multiple visits were necessary to complete a CM visit, and participants earned between $10-$350 during intervention. Only 1 participant self-directed discharge without antibiotic completion. Most participants reported CM “extremely effective” in supporting antibiotic completion, though were more likely to describe CM as moderately effective (range 5-8/10) in addressing drug use reduction. Conclusion: CM for patients with stimulant and/or opioid use disorders needing prolonged antibiotics in acute care settings may be effective in supporting antibiotic completion, and additional exploration is needed to understand both program feasibility and its role in supporting reduced drug use for participants after discharge. Disclosures: All Authors: No reported disclosures.

ObjectiveThe authors sought to determine the efficacy of targeted naltrexone in sexual and gender minority men (SGM) who binge drink and have mild to moderate alcohol use disorder.MethodsIn a double-blind placebo-controlled trial, a total of 120 SGM who binge drink and have mild to moderate alcohol use disorder were randomized in a 1:1 ratio to receive targeted oral naltrexone (50 mg) or placebo with weekly counseling for 12 weeks. The study's primary endpoints were binge-drinking intensity, defined as 1) number of drinks in the past 30 days; 2) any binge drinking in the past week; 3) number of binge-drinking days in the past week; and 4) number of drinking days in the past week. The study also measured changes in alcohol use with two alcohol biomarker measures: ethyl glucuronide in urine samples and phosphatidylethanol (PEth) in dried blood spot samples.ResultsNinety-three percent completed the trial, with 85% of weekly follow-up visits completed. In intention-to-treat analyses, naltrexone was associated with a significantly reduced reported number of binge-drinking days (incidence rate ratio [IRR]=0.74, 95% CI=0.56, 0.98; number needed to treat [NNT]=2), weeks with any binge drinking (IRR=0.83, 95% CI=0.72, 0.96; NNT=7.4), number of drinks per month (IRR=0.69, 95% CI=0.52, 0.91; NNT=5.7 for 10 drinks), and alcohol craving scores (coefficient=-9.25, 95% CI=-17.20, -1.31). In as-treated analyses among those who took their medication on average at least 2.5 days per week (the median frequency in the study), naltrexone reduced any binge drinking (IRR=0.84, 95% CI=0.71, 0.99), number of binge-drinking days (IRR=0.67, 95% CI=0.47, 0.96), and PEth concentrations (coefficient=-55.47, 95% CI=-110.75, -0.20). At 6 months posttreatment, naltrexone had sustained effects in number of drinks per month (IRR=0.69, 95% CI=0.50, 0.97), number of binge-drinking days (IRR=0.67, 95% CI=0.47, 0.95), and any binge drinking in the past week (IRR=0.79, 95% CI=0.63, 0.99).ConclusionsTargeted naltrexone significantly reduced drinking outcomes among SGM with mild to moderate alcohol use disorder during treatment, with sustained effects at 6 months posttreatment. Naltrexone may be an important pharmacotherapy to address binge drinking in populations with mild to moderate alcohol use disorder.

BackgroundChronic 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.MethodsWe 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.ResultsFifty-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.ConclusionStimulants 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.

BackgroundDrug-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).MethodsWe 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.ResultsCocaine-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

ContextCardiovascular 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 methodsWe 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.ResultsMedian 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.ConclusionResults 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.

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.

OBJECTIVES: Fear and risk of precipitated withdrawal are barriers for initiating buprenorphine in individuals with opioid use disorder, particularly among those using fentanyl. A buprenorphine rapid overlap initiation (ROI) protocol (also knownas rapidmicro-dosing) utilizing small, escalating doses of buprenorphine can overcome this barrier, reaching therapeutic doses in 3 to 4 days. We sought to demonstrate the feasibility of implementing a buprenorphine ROI protocol for buprenorphine initiation in the outpatient setting. METHODS: We conducted a retrospective chart review of patients prescribed an outpatient ROI protocol at the Office-based Buprenorphine Induction Clinic from October to December 2020. The ROI protocol utilizes divided doses of sublingual buprenorphine tablets and blister packaging for easier dosing. Patients were not required to stop other opioid use and were advised to follow up on day 4 of initiation. RESULTS: Twelve patients were included, of whom eleven (92%) were using fentanyl at intake. Eleven patients picked up their prescription. Seven patients returned for follow-up (58%), and all 7 completed the ROI protocol. One patient reported any withdrawal symptoms, which were mild. At 30 days, 7 patients (58%) were retained in care, and 5 (42%) were still receiving buprenorphine treatment, 4 (33%) of whom had been abstinent from nonprescribed opioid use for ≥2 weeks. CONCLUSIONS: The ROI protocol was successful in initiating buprenorphine treatment for patients in our outpatient clinic, many of whom were using fentanyl. The ROI protocol may offer a safe alternative to traditional buprenorphine initiation and warrants further study.

BackgroundCardiovascular disease (CVD) and heart failure (HF) are disproportionately high in people living with HIV and differ by sex. Few CVD-related studies focus on drug use, yet it is common in low-income women living with HIV (WLWH) and increases cardiac dysfunction.SettingWe recruited unsheltered and unstably housed WLWH from San Francisco community venues to participate in a six-month cohort study investigating linkages between drug use, inflammation, and cardiac dysfunction.MethodsAdjusting for CVD risk factors, co-infections, medications, and menopause, we examined the effects of toxicology-confirmed drug use and inflammation (C-reactive protein, sCD14, sCD163 and sTNFR2) on levels of NT-proBNP, a biomarker of cardiac stretch and HF.ResultsAmong 74 WLWH, the median age was 53 years and 45 % were Black. At baseline, 72 % of participants had hypertension. Substances used included tobacco (65 %), cannabis (53 %), cocaine (49 %), methamphetamine (31 %), alcohol (28 %), and opioids (20 %). Factors significantly associated with NT-proBNP included cannabis use (Adjusted Relative Effect [ARE]: -39.6 %) and sTNFR2 (ARE: 65.5 %). Adjusting for heart failure and restricting analyses to virally suppressed persons did not diminish effects appreciably. Cannabis use was not significantly associated with sTNFR2 and did not change the association between sTNFR2 and NT-proBNP.ConclusionsAmong polysubstance-using WLWH, NT-proBNP levels signaling cardiac stretch were positively associated with sTNFR2, but 40 % lower in people who used cannabis. Whether results suggest that cardiovascular pathways associated with cannabis use mitigate cardiac stress and dysfunction independent of inflammation in WLWH who use multiple substances merits further investigation.

BackgroundFentanyl has replaced most other non-prescribed opioids in much of North America. There is controversy over whether a hypothetical reduced efficacy of naloxone in reversing fentanyl is a major contributor to the coincident rising overdose mortality.MethodsWe modified an existing Markov decision analytic model of heroin overdose and naloxone distribution to account for known risks of fentanyl by adjusting overdose risk, the likelihood of death in the event of overdose, and the proportion of cases in which available naloxone was administered in time to prevent death. We assumed near-universal survival when naloxone was administered promptly for heroin or fentanyl overdose, but allowed that to decline in sensitivity analyses for fentanyl. We varied the proportion of use that was fentanyl and adjusted the modified parameters accordingly to estimate mortality as the dominant opioid shifted.ResultsAbsent naloxone, the annual overdose death rate was 1.0% and 4.1% for heroin and fentanyl, respectively. With naloxone reaching 80% of those at risk, the overdose death rate was 0.7% and 3.6% for heroin and fentanyl, respectively, representing reductions of 26.4% and 12.0%. Monte Carlo simulations resulted in overdose mortality with fentanyl of 3.3-5.2% without naloxone and 2.6-4.9% with naloxone, with 95% certainty. Positing reduced efficacy for naloxone in reversing fentanyl resulted in 3.6% of fentanyl overdose deaths being prevented by naloxone.ConclusionsHeightened risk for overdose and subsequent death, alongside the time-sensitive need for naloxone administration, fully account for increased mortality when fentanyl replaces heroin, assuming optimal pharmacologic efficacy of naloxone.

INTRODUCTION: People with opioid use disorder (OUD) have high rates of discharge against medical advice from the hospital. Interventions for addressing these patient-directed discharges (PDDs) are lacking. We sought to explore the impact of methadone treatment for OUD on PDD. METHODS: Using electronic record and billing data from an urban safety-net hospital, we retrospectively examined the first hospitalization on a general medicine service for adults with OUD from January 2016 through June 2018. Associations with PDD compared to planned discharge were examined using multivariable logistic regression. Administration patterns of maintenance therapy versus new in-hospital initiation of methadone were examined using bivariate tests. RESULTS: During the study time period, 1,195 patients with OUD were hospitalized. 60.6% of patients received medication for OUD, of which 92.8% was methadone. Patients who received no treatment for OUD had a 19.1% PDD rate while patients initiated on methadone in-hospital had a 20.5% PDD rate and patients on maintenance methadone during the hospitalization had a 8.6% PDD rate. In multivariable logistic regression, methadone maintenance was associated with lower odds of PDD compared to no treatment (aOR 0.53, 95% CI 0.34-0.81), while methadone initiation was not (aOR 0.89, 95% CI 0.56-1.39). About 60% of patients initiated on methadone received 30 mg or less per day. CONCLUSIONS: In this study sample, maintenance methadone was associated with nearly a 50% reduction in the odds of PDD. More research is needed to assess the impact of higher hospital methadone initiation dosing on PDD and if there is an optimal protective dose.

BackgroundPersons 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.MethodsWe 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).ResultsOf 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

BackgroundDespite the high burden of Staphylococcus aureus infections among persons who use drugs, limited data exist comparing outcomes of patient-directed discharge (known as discharge against medical advice) compared with standard discharge among persons who use drugs hospitalized with S. aureus infection.MethodsWe conducted a retrospective study of hospitalizations among adults with S. aureus bacteremia, endocarditis, epidural abscess, or vertebral osteomyelitis at 2 San Francisco hospitals between 2013 and 2018. We compared odds of 1-year readmission for infection persistence or recurrence and 1-year mortality via multivariable logistic regression models adjusting for age, sex, Charlson comorbidity index, and homelessness.ResultsOverall, 80 of 340 (24%) of hospitalizations for invasive S. aureus infections among persons who use drugs involved patient-directed discharge. More than half of patient-directed discharges 41 of 80 (51%) required readmission for persistent or recurrent S. aureus infection compared with 54 of 260 (21%) patients without patient-directed discharge (adjusted odds ratio 3.8, 95% confidence interval [CI] 2.2-6.7). One-year cumulative mortality was 15% after patient-directed discharge compared with 11% after standard discharge (P = .02); however, this difference was not significant after adjustment for mortality risk factors. More than half of deaths in the patient-directed discharge group (7 of 12, 58%) were due to drug overdose; none was due to S. aureus infection.ConclusionsAmong persons who use drugs hospitalized with invasive S. aureus infection, odds of hospital readmission for infection were almost 4-fold higher following patient-directed discharge compared with standard discharge. All-cause 1-year mortality was similarly high in both groups, and drug overdose was a common cause of death in patient-directed discharge group.

AIMS: To evaluate associations between new types of buprenorphine waivers (nurse practitioner and physician assistant [NP/PA]; 275-patient limit [MD/DO-275]) and both buprenorphine prescribing and health outcomes. METHODS: Using comprehensive county-level data from California 2010-2018, we modeled quarterly associations between numbers of NP/PA and MD/DO-275 waivers and rates of buprenorphine prescribing, opioid-related deaths, emergency department (ED) visits, and hospitalizations among all counties and separately among metropolitan and nonmetropolitan counties using Poisson regression models with county and quarter fixed effects and adjusting for time-varying covariates. RESULTS: Each additional NP/PA and MD/DO-275 waiver was associated with a 2.6% (95%CI: 1.1-4.1%) and 5.8% (4.1-7.4%) increase in buprenorphine prescribing among nonmetropolitan counties, respectively. Each additional MD/DO-275 waiver was associated with a 2.8% (1.0%-4.6%) increase in buprenorphine among metropolitan counties. There were no statistically significant associations between NP/PA waivers and buprenorphine prescribing among metropolitan counties or among either waiver type and opioid-related health outcomes. CONCLUSIONS: NP/PA waivers were associated with increased buprenorphine prescribing among nonmetropolitan counties and MD/DO-275 waivers were associated with increased buprenorphine prescribing among both metropolitan and nonmetropolitan counties.

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.

Introduction: In response to the ongoing opioid overdose crisis, US officials urged the expansion of access to naloxone for opioid overdose reversal. Since then, emergency medical services’ (EMS) dispensing of naloxone kits has become an emerging harm reduction strategy.  Methods: We created a naloxone training and low-barrier distribution program in San Francisco: Project FRIEND (First Responder Increased Education and Naloxone Distribution). The team assembled an advisory committee of stakeholders and subject-matter experts, worked with local and state EMS agencies to augment existing protocols, created training curricula, and developed a naloxone-distribution data collection system. Naloxone kits were labeled for registration and data tracking. Emergency medical technicians and paramedics were asked to distribute naloxone kits to any individuals (patient or bystander) they deemed at risk of experiencing or witnessing an opioid overdose, and to voluntarily register those kits.  Results: Training modalities included a video module (distributed to over 700 EMS personnel) and voluntary, in-person training sessions, attended by 224 EMS personnel. From September 25, 2019–September 24, 2020, 1,200 naloxone kits were distributed to EMS companies. Of these, 232 kits (19%) were registered by EMS personnel. Among registered kits, 146 (63%) were distributed during encounters for suspected overdose, and 103 (44%) were distributed to patients themselves. Most patients were male (n = 153, 66%) and of White race (n = 124, 53%); median age was 37.5 years (interquartile range 31-47). Conclusion: We describe a successful implementation and highlight the feasibility of a low-threshold, leave-behind naloxone program. Collaboration with multiple entities was a key component of the program’s success.

BackgroundUS rates of overdose deaths involving stimulants (e.g., cocaine or methamphetamine) have increased, but little is known about non-fatal stimulant overdoses, particularly among vulnerable populations. We characterized rates of non-fatal stimulant overdose identified outside of health care settings among women at high risk.MethodsHomeless and unstably housed women in San Francisco, California using stimulants were administered questionnaires on drug use and outcomes (stimulant overdose, health care utilization) monthly for six months. Based on pilot interviews, stimulant overdose during follow-up was defined as acute toxicity from stimulant use ("over-amping") resulting in "feeling sick, really scared, or like one's life may be in danger". Poisson regression estimated unadjusted incidence rate ratio (IRR) comparing participant characteristics.ResultsWe included 160 women (41% Black, 26% White, 15% Latina, median age 54 years) using crack cocaine (81%), methamphetamine (48%), and powdered cocaine (36%). Participants reported 67 non-fatal stimulant overdoses over 685 person-months of observation, a rate of 117.4 per 100 person-years (95% CI 85.8-160.5). Rates were higher among participants who were Latina vs. White (IRR 4.18 [1.60-10.94]), used methamphetamine (IRR 1.80 [0.96-3.38]), or used any stimulant daily/almost daily (IRR 2.63 [1.41-4.91]). Among women reporting stimulant overdose, 4% received emergency and 3% inpatient care for overdose of any drug.ConclusionsWomen in this setting, particularly those who used stimulants frequently or used methamphetamine, experienced high non-fatal stimulant overdose and rarely received health care for these events. Efforts should be made to increase awareness and reduce harms of stimulant toxicity in vulnerable populations.

IntroductionA better understanding of pain treatment satisfaction in patients with chronic noncancer pain (CNCP) and substance use is needed, especially as opioid prescribing policies are changing. We sought to identify factors associated with pain treatment satisfaction in individuals with CNCP on recent opioid therapy and prior or active substance use.MethodsAn exploratory cross-sectional analysis using baseline data from a cohort study of 300 adults with CNCP receiving >20 morphine milligram equivalents of opioids for ≥3 of the preceding 12 months and prior or active substance use. Participants completed interviews, clinical assessments, urine drug screening, and medical chart review.ResultsParticipants were predominantly middle-aged (mean age 57.5 years), Black (44%), and cisgender men (60%). One-third (33%) had high, 28% moderate, and 39% low pain treatment satisfaction. Post-traumatic stress disorder (PTSD), tobacco use, past-year opioid discontinuation, and higher average pain scores were associated with lower satisfaction. HIV and prescription cannabis use were associated with higher satisfaction.ConclusionsThe relationship between PTSD and tobacco use with lower satisfaction should be explored to augment pain outcomes. Higher satisfaction among individuals with HIV and prescription cannabis use presents potential research areas to guide CNCP management and reduce reliance on opioid therapies.

BACKGROUND: Although death from drug overdose is a leading cause of injury-related death in the United States, its incidence after traumatic incident is unknown. Moreover, little is known about related risk factors. We sought to determine the incidence and characteristics of and risk factors for trauma patients suffering death by acute drug poisoning (overdose) after hospitalization for a traumatic incident. METHODS: We conducted a retrospective chart review of all admitted trauma patients ≥18 y of age at the only level-1 trauma center in our region from 2012 to 2019, matched with unintentional overdose decedents from the California death registry. We assessed associations between demographic and clinical characteristics with risk of overdose death, using cumulative incidence functions and Fine-Gray subdistribution hazard models. RESULTS: Of 9,860 patients residing in San Francisco, CA, USA, at the time of their trauma activation or admission during the study period, 1,418 died (4.3 per 100 person-years), 107 from unintentional overdose (0.3 per 100 person-years). Overdose decedents were 84% male, 50% white, with a mean age of 48 years at the time of presentation; 20% of deaths occurred within 3 months of hospitalization, and 40% were attributed to a prescription opioid. In multivariate analysis, younger age, male sex, white race, and having undergone a urine drug screening were all associated with subsequent death from overdose. CONCLUSION: During a mean 3.4-year follow-up, the mortality rate from overdose among adult patients with traumatic incidents was 0.3/100 person-years. Trauma hospitalization may serve as an opportunity to screen and initiate prevention, harm reduction, and treatment interventions.

BackgroundRecent changes in opioid prescribing practices in the US may exacerbate disparities in opioid access among Black compared to White patients.MethodsTo evaluate racial disparities in opioid prescribing and stewardship, we used baseline data collected from 2017 to 2019 for a longitudinal cohort of patients with chronic non-cancer pain and a history of illicit substance use. Sociodemographic characteristics, pain, psychological distress, substance use, and opioid prescription practices were compared between Black and White participants. We conducted multivariable logistic regression with race as the outcome. We also compared yellow flag events (opioid-related emergency department visits, illicit substances on urine drug screens, provider-documentation of concerning behaviors) by race.ResultsOver half of participants analyzed were Black (57%) and the remainder White (43%). Participants with worse average pain in the past three months (adjusted odds ratio [AOR]:1.29, 95%CI:1.08-1.55, p = 0.006) had higher odds of being Black. Past-year injection drug use (AOR:0.39, 95%CI:0.16-0.94, p = 0.04) and a higher past-year maximum opioid dose (AOR per 10 morphine milligram equivalents (MME):0.99, 95%CI:0.98-1.00, p = 0.006) were associated with lower odds of being Black. We found no differences by race in the use of opioid stewardship measures or discontinuation of opioids based on yellow flag events.ConclusionLower past-year maximum MME dose, despite higher average pain and less injection drug use, may represent bias away from prescribing opioids for chronic pain among Black patients. This could be due to unmeasured implicit provider bias or patient-level factors (e.g., utilizing non-opioid pain coping strategies or being less likely to request additional opioids).

BackgroundThe use of naltrexone plus bupropion to treat methamphetamine use disorder has not been well studied.MethodsWe 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.ResultsA 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

ObjectiveTo determine if men who have sex with men (MSM) with cocaine use disorder (CUD) and actively-using cocaine could be enrolled and retained in a pharmacologic intervention trial of lorcaserin-a novel 5-HT2cR agonist-and determine the degree to which participants would adhere to study procedures.MethodsThis was a phase II randomized, double-blind, placebo-controlled pilot study with 2:1 random parallel group assignment to daily extended-release oral lorcaserin 20 mg versus placebo (clinicaltrials.gov identifier-NCT03192995). Twenty-two of a planned 45 cisgender MSM with CUD were enrolled and had weekly follow-up visits during a 12-week treatment period, with substance use counseling, urine specimen collection, and completion of audio-computer assisted self-interview (ACASI) behavioral risk assessments. Adherence was measured by medication event monitoring systems (MEMS) caps and self-report. This study was terminated early because of an FDA safety alert for lorcaserin's long-term use.ResultsEighty-six percent completed the trial, with 82% of weekly study follow-up visits completed. Adherence was 55.3% (lorcaserin 51.6% vs. placebo 66.2%) by MEMS cap and 56.9% (56.5% vs. placebo 57.9%) by self-report and did not differ significantly by treatment assignment. Intention-to-treat analyses (ITT) did not show differences in cocaine positivity by urine screen between the lorcaserin and placebo groups by 12 week follow-up (incidence risk ratio [IRR]: 0.96; 95%CI = 0.24-3.82, P = 0.95). However, self-reported cocaine use in timeline follow-back declined more significantly in the lorcaserin group compared to placebo (IRR: 0.66; 95%CI = 0.49-0.88; P = 0.004).ConclusionWe found that it is feasible, acceptable, and tolerable to conduct a placebo-controlled pharmacologic trial for MSM with CUD who are actively using cocaine. Lorcaserin was not associated with significant reductions in cocaine use by urine testing, but was associated with significant reductions in self-reported cocaine use. Future research may be needed to continue to explore the potential utility of 5-HT2cR agonists.

IntroductionThe use of controlled substances like cocaine increases the risk of cardiovascular disease (CVD) and myocardial infarction (MI). However, outside of alcohol and tobacco, substance use is not included in CVD risk assessment tools. We identified the effects of using multiple substances (nicotine/cotinine, cannabis, alcohol, cocaine, methamphetamine, heroin and other opioids) on cardiac injury measured by high-sensitivity troponin (hsTnI) in homeless and unstably housed women.MethodsWe recruited 245 homeless and unstably housed women from shelters, free meal programs and street encampments. Participants completed six monthly study visits. Adjusting for traditional CVD risk factors, we examined longitudinal associations between substance use and hsTnI.ResultsMedian participant age was 53 years and 74 % were ethnic minority women. At baseline, 76 % of participants had hypertension, 31 % were HIV-positive, 8% had a history of a prior MI and 12 % of prior stroke. The most commonly used substances were cotinine/nicotine (80 %), cannabis (68 %) and cocaine (66 %). HsTnI exceeding the 99th percentile (14.7 ng/L) - a level high enough to signal possible MI - was observed in 14 participants during >1 study visit (6%). In adjusted analysis, cocaethylene and fentanyl were significantly associated with higher hsTnI levels.ConclusionsFentanyl use and the co-use of cocaine and alcohol are associated with myocardial injury, suggesting that the use of these substances may act as long-term cardiac insults. Whether risk counseling on these specific substances and/or including their use in CVD risk stratification would improve CVD outcomes in populations where substance use is high merits further investigation.

Despite elevated mortality in people with HIV (PWH) using drugs, drug-related deaths are poorly characterized. Among 6764 drug-related deaths, methamphetamine was more common in PWH than others. One in 4 deaths in PWH involved acute infection. Combatting mortality in PWH who use drugs should include stimulant-specific and infection prevention efforts.

BackgroundNumerous 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.MethodsWe 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.ResultsOut 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.ConclusionsThe 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.

BackgroundOpioid overdose mortality continues to increase in the United States despite significant investments to reverse the epidemic. The national response to-date has focused primarily on reducing opioid prescribing, yet reductions in prescribing have been associated with patients reporting uncontrolled pain, psychological distress, and transition to illicit substances. The aim of this study is to qualitatively explore chronic pain management experiences among PLWH with a history of illicit substance use after long-term opioid therapy reductions or discontinuations.MethodsWe analyzed 18 interviews, stopping upon reaching thematic saturation, with HIV-positive participants with a history of substance use who were enrolled in a longitudinal cohort study to assess the impact of prescribing changes among patients with chronic pain. Participants in this nested qualitative study had been reduced/discontinued from opioid pain relievers (OPRs) within the 12 months prior to interview. Interviews were audio-recorded and transcribed verbatim. Two analysts coded all interviews, interrater reliability was measured, and coding discrepancies discussed. The study took place in San Francisco, California in 2018.ResultsEleven participants were male with a mean age of 55; 8 were African American and 8 were White. All participants were HIV-positive, actively engaged in primary care, and had a lifetime history of illicit substance use. Twelve reported using illicit substances within the past year, including non-prescription opioids/heroin (10), and stimulant use (10). After being reduced/discontinued from their long-term opioid therapy, patients reported developing complex multimodal pain management systems that often included both nonpharmacological approaches and illicit substance use. Participants encountered a range of barriers to nonpharmacological therapies including issues related to accessibility and availability. Participants often reported attempts to replicate their prior OPR prescription by seeking out the same medication and dose from illicit sources and reported transitioning to heroin after exhausting other options.ConclusionAfter being reduced/discontinued from OPRs, HIV-positive patients with a history of substance use reported experimenting with a range of pain management modalities including nonpharmacological therapies and illicit substance use to manage symptoms of opioid withdrawal and pain. Providers should consider that any change to a patients' long-term opioid therapy may result in experimentation with pain management outside of the medical setting and may want to employ patient-centered, holistic approaches when managing patients' opioid prescriptions and chronic pain.

BackgroundTo apply a novel method to adjust for HIV knowledge as an unmeasured confounder for the effect of unsafe injection on future HIV testing.MethodsThe data were collected from 601 HIV-negative persons who inject drugs (PWID) from a cohort in San Francisco. The panel-data generalized estimating equations (GEE) technique was used to estimate the adjusted risk ratio (RR) for the effect of unsafe injection on not being tested (NBT) for HIV. Expert opinion quantified the bias parameters to adjust for insufficient knowledge about HIV transmission as an unmeasured confounder using Bayesian bias analysis.ResultsExpert opinion estimated that 2.5%-40.0% of PWID with unsafe injection had insufficient HIV knowledge; whereas 1.0%-20.0% who practiced safe injection had insufficient knowledge. Experts also estimated the RR for the association between insufficient knowledge and NBT for HIV as 1.1-5.0. The RR estimate for the association between unsafe injection and NBT for HIV, adjusted for measured confounders, was 0.96 (95% confidence interval: 0.89,1.03). However, the RR estimate decreased to 0.82 (95% credible interval: 0.64, 0.99) after adjusting for insufficient knowledge as an unmeasured confounder.ConclusionOur Bayesian approach that uses expert opinion to adjust for unmeasured confounders revealed that PWID who practice unsafe injection are more likely to be tested for HIV - an association that was not seen by conventional analysis.

BackgroundAfter decades of increased opioid pain reliever prescribing, providers are rapidly reducing prescribing. We hypothesized that reduced access to prescribed opioid pain relievers among patients previously reliant upon opioid pain relievers would result in increased illicit opioid use.Methods and findingsWe conducted a retrospective cohort study among 602 publicly insured primary care patients who had been prescribed opioids for chronic non-cancer pain for at least three consecutive months in San Francisco, recruited through convenience sampling. We conducted a historical reconstruction interview and medical chart abstraction focused on illicit substance use and opioid pain reliever prescriptions, respectively, from 2012 through the interview date in 2017-2018. We used a nested-cohort design, in which patients were classified, based on opioid pain reliever dose change, into a series of nested cohorts starting with each follow-up quarter. Using continuation-ratio models, we estimated associations between opioid prescription discontinuation or 30% increase or decrease in dose, relative to no change, and subsequent frequency of heroin and non-prescribed opioid pain reliever use, separately. Models controlled for demographics, clinical and behavioral characteristics, and past use of heroin or non-prescribed opioid pain relievers. A total of 56,372 and 56,484 participant-quarter observations were included from the 597 and 598 participants available for analyses of heroin and non-prescribed opioid pain reliever outcomes, respectively. Participants discontinued from prescribed opioids were more likely to use heroin (Adjusted Odds Ratio (AOR) = 1.57, 95% CI: 1.25-1.97) and non-prescribed opioid pain relievers (AOR = 1.75, 1.45-2.11) more frequently in subsequent quarters compared to participants with unchanged opioid prescriptions. Participants whose opioid pain reliever dose increased were more likely to use heroin more frequently (AOR = 1.67, 1.32-2.12). Results held throughout sensitivity analyses. The main limitations were the observational nature of results and limited generalizability beyond safety-net settings.ConclusionsDiscontinuation of prescribed opioid pain relievers was associated with more frequent non-prescribed opioid pain reliever and heroin use; increased dose was also associated with more frequent heroin use. Clinicians should be aware of these risks in determining pain management approaches.

BACKGROUND: Single room occupancy (SRO) buildings, also known as residential hotels, are a form of affordable housing common to cities in North America, and residents of these buildings face elevated rates of substance use, physical and mental multimorbidity, and mortality. Identifying distinct populations at greater risk of overdose death is crucial to the planning of interventions aiming to reduce drug-related mortality, yet no studies have assessed the population burden of overdose mortality among SRO residents. The present study quantifies and characterizes drug overdose mortality among residents of SRO buildings in a large U.S. city. METHODS: We used mortality records and a database of SRO buildings to calculate rate ratios comparing overdose mortality due to opioids, cocaine, and methamphetamine among SRO residents and non-SRO residents in San Francisco, CA 2010-2017 and assessed bivariate differences in decedent and death location characteristics between SRO resident and other overdose decedents. RESULTS: There were 1,551 overdose deaths during the study period, with an overall rate of 21.3 per 100,000 residents (95%CI = 20.2-22.6). The rate among SRO residents (278.7, 95%CI = 252.9-306.5) was 19.3 (95%CI = 17.1-21.7) times that of non-SRO residents (21.3, 95%CI = 20.2-22.6). An additional 79 (5%) deaths among non-residents occurred in SRO buildings, and 86% of SRO resident decedents died at home compared to 64% of non-SRO residents (p

OBJECTIVE:To understand the number of young adult people who inject drugs (PWID) with hepatitis C virus (HCV) infection accessing direct-acting antiviral (DAA) treatment and their barriers and facilitators to treatment uptake. METHODS:Using prospective cohort data from young adult PWID in San Francisco with newly identified HCV infection, we calculated the number who: (i) accepted referral to DAA therapy, (ii) initiated DAA therapy, (iii) completed DAA therapy, and (iv) achieved sustained virologic response (SVR) or cure. Behavioral survey data identified possible barriers and facilitators to DAA therapy. RESULTS:Of 60 young adult PWID with new HCV infection identified between February 2015 and January 2018, thirty accepted a referral to HCV care; five initiated and completed HCV treatment and achieved cure. Barriers to DAA uptake included fear of medical establishments, competing basic needs, and delaying care because they were feeling well. CONCLUSION:While few HCV-positive young adult PWID engaged in DAA therapy, all those who did achieved cure. Youth-tailored services that overcome the stigma and marginalization related to injection drug use are needed to improve treatment uptake.

AimsThe advent of direct-acting antivirals for hepatitis C virus (HCV) and limited effectiveness of prevention have generated interest in "Treatment as Prevention" (TasP), in which those most likely to transmit HCV (i.e. people who inject drugs [PWID]) are treated to reduced secondary transmission. However, there are scant data regarding the feasibility of treating PWID at high risk for secondary transmission or the optimal approach to treatment delivery.MethodsWe conducted a 2:1 randomized trial of modified directly-observed (mDOT) versus unobserved HCV treatment with ledipasvir-sofosbuvir daily for 8 weeks among PWID with 36 weeks of follow-up in San Francisco from 2015-2017. We evaluated recruitment-enrollment, treatment completion, end-of-treatment and 12-week response, and reinfection rate.ResultsOf 83 individuals eligible for screening, 72 (87.6%) attended the screening visit, 33 were eligible, and 31 enrolled; mean age was 42 years, 81% were male, 74% white. All but one participant (in the mDOT arm) completed treatment and 89.4% of mDOT and 96.6% of unobserved arm visits were attended. HCV was undetectable for 96.8% (30/31) at end of treatment and 89.7% (26/29) 12 weeks later (1 relapse, 1 reinfection), with no differences by arm. Two additional reinfections were subsequently identified, for a reinfection rate of 16.3 (95% CI 5.3-50.5) per 100 person-years of observation.ConclusionsIt was feasible to recruit active PWID for HCV treatment and achieve high retention, viral response, and satisfaction with either mDOT or unobserved protocols, supporting treatment of PWID at risk of transmitting HCV to others. The reinfection rate suggests we successfully reached a high-risk population and that successful HCV TasP initiatives may aim to be sufficient in scope to significantly lower prevalence in the community.Trial registrationclinicaltrials.gov NCT02609893.

BackgroundSelf-reported data are widely used in substance-use research, yet few studies have assessed the validity of self-reported methamphetamine use compared to biological assays.ObjectivesWe sought to assess the validity and correlates of validity of self-reported methamphetamine use compared to urine toxicology (UTOX).MethodsUsing a sample of methamphetamine-dependent individuals enrolled in a randomized controlled pharmacotherapy trial in the United States (n = 327 visits among 90 participants), we calculated sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and the kappa coefficient of self-reported methamphetamine use in the past 3 days compared to UTOX, as well as the NPV of self-reported methamphetamine use over an extended recall period of 1 month. We used multivariable logistic regression models to assess correlates of concordance between self-reported methamphetamine use and UTOX.ResultsThe sensitivity of self-reported methamphetamine use in the past 3 days was 86.7% (95% confidence intervals (95%CI): 81.4%-91.4%), the specificity was 85.3% (77.7-91.3), the PPV was 91.5% (86.9-94.8), and the NPV was 78.0% (69.4-86.1), compared to UTOX (kappa = 0.71). The NPV over the extended recall period was 70.6% (48.0-85.7). In multivariable analyses, validity of self-reported methamphetamine use was higher for older participants but lower during follow-up compared to baseline and when polysubstance use or depressive symptoms were reported. Conclusions/Importance: Our sample of methamphetamine-dependent adults reported recent methamphetamine use with high validity compared to UTOX. Validity increased with age but decreased when participants reported depressive symptoms or polysubstance use as well as later in the study timeline and during longer recall periods.

BackgroundReduced opioid tolerance is believed to be associated with overdose risk, although this relationship has primarily been examined in the context of gaps and frequency of opioid use. We sought to assess how changes in the quantity of opioids used, as opposed to periods of abstinence or overall frequency of use, relate to overdose risk.MethodsAmong repeated visits of participants of a behavioral intervention trial from 2014 to 2016, we used multivariable logistic regression models fit with generalized estimating equations to examine the relationship between the percentage of opioid use days on which individuals used more or less than the quantity they used on average (i.e., quantity volatility) and the occurrence of opioid overdose.ResultsOur sample included 290 four-month reporting periods among 63 participants (67% male). Opioid overdose events were reported by 28 (44%) participants during 48 (17%) reporting periods. Our measure of quantity volatility had a median of 20% (IQR 0.0-50.0). In multivariable analysis, using a quantity different than the quantity used on average on more than 20% of all opioid use days in the reporting period was significantly associated with odds of any opioid overdose (Adjusted OR = 3.55, 95%CI = 1.55-8.13, p = 0.003), controlling for confounders.ConclusionQuantity volatility of illicitly used opioids was positively associated with overdose risk and may contribute to the complex system of overlapping factors that influence overdose risk. Future observational research among opioid users should collect detailed opioid use data, including quantity used over time, to clarify the patterns that most elevate overdose risk.

BackgroundOpioids and stimulants (e.g., cocaine or methamphetamine/amphetamine [MAMP]) are major contributors to acute substance toxicity deaths. Causes of stimulant death have received little attention. We sought to characterize and compare causes of death and significant contributing conditions among persons who died from acute opioid, cocaine, or MAMP toxicity.MethodsWe identified all opioid, cocaine, or MAMP deaths in San Francisco from 2005 to 2015 through the California Electronic Death Reporting System. Multivariable logistic regression analyses were used to estimate associations between acute substance toxicity deaths (opioid versus stimulant; cocaine versus MAMP), additional reported causes of death, and significant contributing conditions most often linked to opioid and stimulant use.ResultsFrom 2005-2015, there were 1252 opioid deaths and 749 stimulant deaths. Cocaine accounted for most stimulant deaths. Decedents with cardiac or cerebral hemorrhage deaths had higher adjusted odds of death due to acute stimulant toxicity versus acute opioid toxicity (aOR = 4.79, 95%CI = 2.88-7.96, p

Background and aimsMethamphetamine use is increasingly prevalent and associated with HIV transmission. Early-phase human studies suggested naltrexone reduced amphetamine use among dependent individuals. We tested if extended-release naltrexone (XRNTX) reduces methamphetamine use and associated sexual risk behaviors among high-risk methamphetamine-dependent men who have sex with men (MSM).DesignDouble-blind, placebo-controlled, randomized trial of XRTNX versus placebo over 12 weeks from 2012 to 2015.SettingSan Francisco Department of Public Health, California, USA.ParticipantsOne hundred community-recruited, sexually-active, actively-using methamphetamine-dependent MSM. Mean age was 43.2 years; 96% were male, 3% transfemale, and 1% transmale; 55.0% were white, 19.0% African American, and 18.0% Latino.InterventionsXRNTX 380 mg (n = 50) or matched placebo (n = 50) administered by gluteal injection at 4-week intervals.MeasurementsRegression estimated average level and change in level of positive urines during the period 2-12 weeks (primary outcomes) and sexual risk behaviors (secondary outcome).FindingsNinety per cent of visits were completed. By intent-to-treat, participants assigned to XRNTX had similar differences during 2-12 weeks in methamphetamine-positive urines as participants assigned to placebo [incidence rate ratio (IRR) = 0.95, 95% confidence interval (CI) = 0.76-1.20; Bayes factor  0.05). There were no serious adverse events related to study drug and no differences in frequency of adverse events by treatment arm.ConclusionsNotwithstanding very high medication adherence for this study, extended-release naltrexone does not appear to reduce methamphetamine use or sexual risk behaviors among methamphetamine-dependent men who have sex with men compared with placebo.

OBJECTIVES:To describe heavy alcohol use patterns and correlates in a diverse sample of MSM. METHODS:We used respondent-driven sampling (RDS) to enroll 252 alcohol-using MSM in San Francisco from March 2015-July 2017. We examined heavy alcohol use patterns and conducted RDS-adjusted multivariable analyses to characterize correlates of hazardous alcohol consumption and binge drinking. RESULTS:RDS-adjusted prevalence of weekly and at least weekly binge drinking was 24.9% and 19.3%, respectively. Hazardous consumption was common; prevalence of mid- and high-levels of hazardous drinking was 11.4% and 29.9%, respectively. In multivariable analyses, identifying as Hispanic/Latino or mixed/other race; being moderately or extremely interested in reducing alcohol use; ever receiving alcohol treatment; using ecstasy; reporting syphilis diagnosis; and having more than 5 male partners were independently associated with hazardous alcohol consumption. Less hazardous consumption was associated with having a bachelor's degree or completing post-graduate studies; and not being in a relationship. Reporting chlamydia infection; being somewhat, moderately or extremely interested in reducing alcohol use; and having multiple male sex partners were associated with higher odds of at least weekly binge drinking. Lower odds of binge drinking were associated with completing post-graduate studies. Moreover, for the outcomes of hazardous alcohol consumption and binge-drinking, we observed significant interaction effects between race/ethnicity and interest in reducing alcohol, past receipt of alcohol treatment, use of ecstasy, syphilis diagnosis, and number of male partners. CONCLUSION:Among alcohol-using MSM in San Francisco, heavy drinking patterns were common and independently associated with greater number of male sexual partners and sexually transmitted infections (STI). Moreover, significant racial/ethnic and socioeconomic disparities related to heavy alcohol use were observed and race/ethnicity modified the effect of the risk factors associated with these outcomes. These findings underscore the need to develop more MSM-specific interventions that jointly address heavy alcohol use and HIV/STI risk, as well as culturally-tailored and targeted strategies to alleviate health disparities.