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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.

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.

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.

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.

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

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.

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).

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.

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.

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.

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.

BackgroundWhile cocaine use is an established risk factor for acute cardiovascular complications, associations between cocaine use and markers of cardiac injury outside of acute hospital presentation remain poorly characterized. We leveraged advances in cardiac troponin (cTnI) testing to assess low but clinically meaningful levels of cardiac injury among cocaine users and non-users.MethodsWe conducted a case control study comparing cTnI levels by the presence of cocaine among patients presenting for non-cardiac care in an urban safety net hospital. Samples were chosen sequentially among those for which urine drug screens were ordered by providers hospital-wide.ResultsDuring 2015, 14% of all hospital drug screens ordered were cocaine-positive. Among unique persons providing cocaine-positive (N=100) and cocaine-negative (N=100) samples, 37% were female, 45% were African-American and the median age was 51. Detectable cTnI (> 0.02ng/mL) was observed in 21 samples (11%). It was more common in subjects using cocaine (Adjusted OR=2.81; 95% CI=1.03-7.65), but not other drugs. Moreover, there was a significant correlation between concentrations of cTnI and the cocaine metabolite, benzoylecgonine (Spearman Correlation=0.34, p

BackgroundNaloxone co-prescription is recommended for patients on long-term opioids for pain, yet there are few data on the practice.ObjectiveTo explore naloxone co-prescribing acceptability among primary care providers for patients on long-term opioids.DesignWe surveyed providers at six safety-net primary care clinics in San Francisco that had initiated naloxone co-prescribing. Providers were encouraged to offer naloxone to patients on long-term opioids or otherwise at risk of witnessing or experiencing an overdose. Surveys were administered electronically 4 to 11 months after co-prescribing began.Key resultsOne hundred eleven providers (69 %) responded to the survey, among whom 41.4 % were residents; 40.5 % practiced internal medicine and 55.0 % practiced family medicine. Most (79.3 %) prescribed naloxone, to a mean of 7.7 patients; 99.1 % were likely to prescribe naloxone in the future. Providers reported they were likely to prescribe naloxone to most patients, including those on low doses, defined as

Men who have sex with men (MSM) are the demographic group most severely affected by HIV in the USA. Global association studies have shown that MSM who binge drink are more likely to engage in risky sexual behaviors and day- and event-level analyses have linked binge drinking to sexual risk behavior on specific days and during specific sexual encounters. Despite this strong foundation of research, no studies have examined the association between the frequency of situational binge drinking (i.e., binge drinking concurrent with sexual activity) and aggregated sexual risk over periods of longer duration. We used multivariable logistic regression to assess the relationship between situational binge drinking (i.e., binge drinking concurrent with anal intercourse) and condomless anal intercourse (CAI) and among a cross-sectional sample of 124 MSM in San Francisco, CA. There was a positive relationship between frequency of situational binge drinking and CAI (1-5 times vs. never: adjusted odds ratio = 2.78, 95% CI = 1.01-7.63; 6-10 times vs. never: 6.19, 1.27-30.22; more than 10 times vs. never: 11.88, 1.31-107.60). By filling a methodological gap and complementing existing global and event-level analyses, this positive situational relationship strengthens the evidence linking binge drinking and sexual risk, enhances the comparability of the existing literature, and further suggests that the integration of dual strategies that aim to prevent HIV and reduce binge drinking may be warranted.

BackgroundUnintentional overdose involving opioid analgesics is a leading cause of injury-related death in the United States.ObjectiveTo evaluate the feasibility and effect of implementing naloxone prescription to patients prescribed opioids for chronic pain.Design2-year nonrandomized intervention study.Setting6 safety-net primary care clinics in San Francisco, California.Participants1985 adults receiving long-term opioid therapy for pain.InterventionProviders and clinic staff were trained and supported in naloxone prescribing.MeasurementsOutcomes were proportion of patients prescribed naloxone, opioid-related emergency department (ED) visits, and prescribed opioid dose based on chart review.Results38.2% of 1985 patients receiving long-term opioids were prescribed naloxone. Patients prescribed higher doses of opioids and with an opioid-related ED visit in the past 12 months were independently more likely to be prescribed naloxone. Patients who received a naloxone prescription had 47% fewer opioid-related ED visits per month in the 6 months after receipt of the prescription (incidence rate ratio [IRR], 0.53 [95% CI, 0.34 to 0.83]; P = 0.005) and 63% fewer visits after 1 year (IRR, 0.37 [CI, 0.22 to 0.64]; P < 0.001) compared with patients who did not receive naloxone. There was no net change over time in opioid dose among those who received naloxone and those who did not (IRR, 1.03 [CI, 0.91 to 1.27]; P = 0.61).LimitationResults are observational and may not be generalizable beyond safety-net settings.ConclusionNaloxone can be coprescribed to primary care patients prescribed opioids for pain. When advised to offer naloxone to all patients receiving opioids, providers may prioritize those with established risk factors. Providing naloxone in primary care settings may have ancillary benefits, such as reducing opioid-related adverse events.Primary funding sourceNational Institutes of Health.

There were over 23,000 opioid overdose deaths in the USA in 2013, and opioid-related mortality is increasing. Increased access to naloxone, particularly through community-based lay naloxone distribution, is a widely supported strategy to reduce opioid overdose mortality; however, little is known about the ecological and spatial patterns of the distribution and utilization of lay naloxone. This study aims to investigate the neighborhood-level correlates and spatial relationships of lay naloxone distribution and utilization and opioid overdose deaths. We determined the locations of lay naloxone distribution sites and the number of unintentional opioid overdose deaths and reported reversal events in San Francisco census tracts (n = 195) from 2010 to 2012. We used Wilcoxon rank-sum tests to compare census tract characteristics across tracts adjacent and not adjacent to distribution sites and multivariable negative binomial regression models to assess the association between census tract characteristics, including distance to the nearest site, and counts of opioid overdose deaths and naloxone reversal events. Three hundred forty-two opioid overdose deaths and 316 overdose reversals with valid location data were included in our analysis. Census tracts including or adjacent to a distribution site had higher income inequality, lower percentage black or African American residents, more drug arrests, higher population density, more overdose deaths, and more reversal events (all p < 0.05). In multivariable analysis, greater distance to the nearest distribution site (up to a distance of 4000 m) was associated with a lower count of Naloxone reversals [incidence rate ratio (IRR) = 0.51 per 500 m increase, 95% CI 0.39-0.67, p < 0.001] but was not significantly associated with opioid overdose deaths. These findings affirm that locating lay naloxone distribution sites in areas with high levels of substance use and overdose risk facilitates reversals of opioid overdoses in those immediate areas but suggests that alternative delivery methods may be necessary to reach individuals in other areas with less concentrated risk.

AimsTo describe characteristics of participants and overdose reversals associated with a community-based naloxone distribution program and identify predictors of obtaining naloxone refills and using naloxone for overdose reversal.DesignBivariate statistical tests were used to compare characteristics of participants who obtained refills and reported overdose reversals versus those who did not. We fitted multiple logistic regression models to identify predictors of refills and reversals; zero-inflated multiple Poisson regression models were used to identify predictors of number of refills and reversals.SettingSan Francisco, California, USA.ParticipantsNaloxone program participants registered and reversals reported from 2010 to 2013.MeasurementsBaseline characteristics of participants and reported characteristics of reversals.FindingsA total of 2500 participants were registered and 702 reversals were reported from 2010 to 2013. Participants who had witnessed an overdose [adjusted odds ratio (AOR)=2.02, 95% confidence interval (CI)= 1.53-2.66; AOR = 2.73, 95% CI = 1.73-4.30] or used heroin (AOR = 1.85, 95% CI =  1.44-2.37; AOR = 2.19, 95% CI = 1.54-3.13) or methamphetamine (AOR=1.71, 95% CI=1.37-2.15; AOR=1.61, 95% CI=1.18-2.19) had higher odds of obtaining a refill and reporting a reversal, respectively. African American (AOR = 0.63, 95% CI = 0.45-0.88) and Latino (AOR = 0.65, 95% CI =  0.43-1.00) participants had lower odds of obtaining a naloxone refill, whereas Latino participants who obtained at least one refill reported a higher number of refills [incidence rate ratio (IRR) = 1.33 (1.05-1.69)].ConclusionsCommunity naloxone distribution programs are capable of reaching sizeable populations of high-risk individuals and facilitating large numbers of overdose reversals. Community members most likely to engage with a naloxone program and use naloxone to reverse an overdose are active drug users.

Episodic drug use and binge drinking are associated with HIV risk among substance-using men who have sex with men (SUMSM), yet no evidence-based interventions exist for these men. We adapted personalized cognitive counseling (PCC) to address self-justifications for high-risk sex among HIV-negative, episodic SUMSM, then randomized men to PCC (n = 162) with HIV testing or control (n = 164) with HIV testing alone. No significant between-group differences were found in the three primary study outcomes: number of unprotected anal intercourse events (UAI), number of UAI partners, and UAI with three most recent non-primary partners. In a planned subgroup analysis of non-substance dependent men, there were significant reductions in UAI with most recent non-primary partners among PCC participants (RR = 0.56; 95 %CI 0.34-0.92; P = 0.02). We did not find evidence that PCC reduced sexual risk behaviors overall, but observed significant reductions in UAI events among non-dependent SUMSM. PCC may be beneficial among SUMSM screening negative for substance dependence.

BackgroundNon-dependent alcohol and substance use patterns are prevalent among men who have sex with men (MSM), yet few effective interventions to reduce their substance use are available for these men. We evaluated whether an adapted brief counseling intervention aimed at reducing HIV risk behavior was associated with secondary benefits of reducing substance use among episodic substance-using MSM (SUMSM).Methods326 episodic SUMSM were randomized to brief Personalized Cognitive Counseling (PCC) intervention with rapid HIV testing or to rapid HIV testing only control. Both arms followed over 6 months. Trends in substance use were examined using GEE Poisson models with robust standard errors by arm. Reductions in frequency of use were examined using ordered logistic regression.ResultsIn intent-to-treat analyses, compared to men who received rapid HIV testing only, we found men randomized to PCC with rapid HIV testing were more likely to report abstaining from alcohol consumption (RR=0.93; 95% CI=0.89-0.97), marijuana use (RR=0.84; 95% CI=0.73-0.98), and erectile dysfunction drug use (EDD; RR=0.51; 95% CI=0.33-0.79) over the 6-month follow-up. PCC was also significantly associated with reductions in frequency of alcohol intoxication (OR=0.58; 95% CI=0.36-0.90) over follow-up. Furthermore, we found PCC was associated with significant reductions in number of unprotected anal intercourse events while under the influence of methamphetamine (RR=0.26; 95% CI=0.08-0.84).ConclusionThe addition of adapted PCC to rapid HIV testing may have benefits in increasing abstinence from certain classes of substances previously associated with HIV risk, including alcohol and EDD; and reducing alcohol intoxication frequency and high-risk sexual behaviors concurrent with methamphetamine use.

We evaluated the relationship between frequency and number of substances used and HIV risk [ie, serodiscordant unprotected anal intercourse (SDUAI)] among 3173 HIV-negative substance-using MSM. Compared with nonusers, the adjusted odds ratio (AOR) for SDUAI among episodic and at least weekly users, respectively, was 3.31 [95% confidence interval (CI), 2.55 to 4.28] and 5.46 (95% CI, 3.80 to 7.84) for methamphetamine, 1.86 (95% CI, 1.51 to 2.29) and 3.13 (95% CI, 2.12 to 4.63) for cocaine, and 2.08 (95% CI, 1.68 to 2.56) and 2.54 (95% CI, 1.85 to 3.48) for poppers. Heavy alcohol drinkers reported more SDUAI than moderate drinkers [AOR, 1.90 (95% CI, 1.43 to 2.51)]. Compared with nonusers, AORs for using 1, 2, and ≥3 substances were 16.81 (95% CI, 12.25 to 23.08), 27.31 (95% CI, 18.93 to 39.39), and 46.38 (95% CI, 30.65 to 70.19), respectively. High-risk sexual behaviors were strongly associated with frequency and number of substances used.

Objectives: To develop and assess a housestaff curriculum on opioid and other substance abuse among patients with chronic noncancer pain (CNCP). Methods: The two-hour, case-based curriculum delivered to small groups of medical housestaff sought to improve assessment and management of opioid-treated CNCP patients, including those with a substance use disorder. A two-page pre-post survey was administered to assess self-efficacy change on a scale from 1 (strongly disagree) to 5 (strongly agree). Results: Of 47/50 (94%) respondents, self-efficacy significantly improved across all items (mean pre vs. post ratings, P less than 0.001). Housestaff were more prepared to manage patients on chronic opioid medication (2.8 vs. 3.8), including those with substance use disorders (2.3 vs. 3.4). They felt more prepared to identify opioid dependence (2.8 vs. 3.9) and overall rated the curriculum favorably (4.2). Conclusions: The brief curriculum was well received and appears effective. Further study is needed to determine practice impact. (Contains 4 tables and 8 online resources.)

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. [ABSTRACT FROM AUTHOR]