Christopher Rowe

Prevalence and correlates of substance use among trans*female youth ages 16–24 years in the San Francisco Bay Area

BACKGROUND Substance use is highly prevalent among transgender (trans*) females and has been associated with negative health outcomes, including HIV infection. Little is known about psychosocial risk factors that may influence the onset of substance use among trans*female youth, which can contribute to health disparities during adulthood. METHODS We conducted a secondary data analysis of a study on HIV risk and resilience among trans*female youth (N=292). Prevalence of substance use was assessed and multivariable logistic regression models were used to examine the relationship between posttraumatic stress disorder (PTSD), psychological distress, gender-related discrimination, parental drug or alcohol problems (PDAP) and multiple substance use outcomes. RESULTS Most (69%) of the trans*female youth reported recent drug use. In multivariable analyses, those with PTSD had increased odds of drug use [AOR=1.94 (95% CI=1.09-3.44)]. Those who experienced gender-related discrimination had increased odds of drug use [AOR=2.28 (95% CI=1.17-4.44)], drug use concurrent with sex [AOR=2.35 (95% CI=1.11-4.98)] and use of multiple drugs [AOR=3.24 (95% CI=1.52-6.88)]. Those with psychological distress had increased odds of using multiple heavy drugs [AOR=2.27 (95% CI=1.01-5.12)]. Those with PDAP had increased odds of drugs use [AOR=2.62 (95% CI=1.43-4.82)], drug use concurrent with sex [AOR=2.01 (95% CI, 1.15-3.51)] and use of multiple drugs [AOR=2.10 (95% CI=1.22-3.62)]. CONCLUSIONS Substance use is highly prevalent among trans*female youth and was significantly associated with psychosocial risk factors. In order to effectively address substance use among trans*female youth, efforts must address coping related to gender-based discrimination and trauma. Furthermore, structural level interventions aiming to reduce stigma and gender-identity discrimination might also be effective.

Nonrandomized Intervention Study of Naloxone Coprescription for Primary Care Patients Receiving Long-Term Opioid Therapy for Pain

In the United States, the opioid analgesic overdose death rate increased from 1.4 to 5.4 per 100000 adults from 1999 to 2011 (1). Efforts to manage this increase in mortality have focused on modifying the prescribing practices of providers (2). Mandated urine testing, pain agreements, and inspections of prescription drug monitoring program data have become standard practice, yet few data support a link between such interventions and reduced opioid-related morbidity or mortality. In fact, whereas opioid analgesic deaths have recently plateaued, heroin use and overdose deaths have skyrocketed, suggesting possible unintended consequences of opioid stewardship initiatives (3, 4). Many communities have used the targeted distribution of naloxone, the short-acting opioid antagonist, to address opioid-related mortality (5). Provision of naloxone to those likely to witness or experience an opioid overdose, principally illicit drug users, has been associated with substantial reductions in community-level opioid overdose mortality relative to communities that did not implement naloxone distribution (6). Other observational and ecologic analyses have demonstrated marked reductions in opioid overdose mortality in communities that distributed naloxone, including Chicago, Illinois (7); New York City (8); and Scotland (9). A meta-analysis demonstrated a higher likelihood of survival in overdose situations when naloxone was administered by laypersons (10). Naloxone distribution to heroin users is remarkably cost-effective (11). In San Francisco, California, implementation and expansion of a targeted naloxone distribution program were temporally associated with a decline in heroin overdose deaths from as high as 180 per year to as few as 10 through 2012. The number of deaths attributed to opioid analgesics, however, exceeded 100 annually from 2010 to 2012 (12). Most of these decedents had received primary care in safety-net clinics, and most had received long-term opioid therapy for pain. However, literature to support naloxone prescribing to this population is limited to early descriptive analyses (13) and anecdotal reports (14). At U.S. Army Fort Bragg, overdoses seen in the emergency department (ED) declined from 8 per month to 0 after naloxone coprescription was started (14, 15); this finding suggests that naloxone prescription may have affected the overdose event rate by influencing patient and/or provider behavior, rather than simply being available as a reversal agent. These results are consistent with some data indicating that heroin users who receive naloxone reduce heroin use (16). In response to these data, we developed and coordinated a standardized naloxone coprescribing program at primary care clinics in a safety-net system in San Francisco. To inform the larger-scale implementation of naloxone prescribing for patients prescribed opioid medications, we assessed the feasibility of introducing and scaling up naloxone coprescribing in these primary care clinics and conducted analyses to assess the association of naloxone coprescribing with ED use and prescribed opioid dose. Methods Naloxone for Opioid Safety Evaluation (NOSE) staff coordinated the clinical program and conducted the evaluation. The study was approved by the Committee on Human Research of the University of California, San Francisco (CHR#13-11168). Clinical Program The clinical program was implemented in a rolling fashion from February 2013 to April 2014 at 6 clinics where patients had died of opioid overdose from 2010 to 2012. All clinics accepted only publicly insured or uninsured patients, and 2 were resident training sites. Onsite leaders were selected, and a consistent protocol was implemented across sites, beginning with training in naloxone prescribing for providers (physicians, nurse practitioners, and physician assistants) and staff (see Appendix and Appendix Table 1, for implementation plan and process outcomes). Training covered rationale and indications for prescribing naloxone (anyone who uses opioids long term or is otherwise at risk for witnessing or experiencing an opioid overdose), language to approach patients (for example, use such phrases as bad reaction instead of overdose), naloxone formulations, and pharmacy/payer coverage. Additionally, providers and staff were trained on how to educate patients on naloxone use, how to assemble the intranasal device (the U.S. Food and Drug Administration has since approved a device requiring no assembly [17]), and ensuring that caretakers know how and when to administer naloxone (Appendix Figure 1). Appendix Figure 1. Checklist for clinic staff to train patients receiving naloxone. CPR = cardiopulmonary resuscitation. Appendix Table 1. Implementation Plan and Process Outcomes for Naloxone Coprescribing at Safety-Net Clinics Initial training was provided to all sites approximately 30 days preceding initiation of naloxone coprescription; after initiation, additional training was provided and at least 1 reminder e-mail was sent to providers (Appendix Figure 2). Because most providers opted to prescribe the intranasal formulation of naloxone and the mucosal atomization device was not readily available from pharmacies, clinics could order the device and patient brochures (Appendix Figure 3) in zipper-seal plastic bags from the clinic systems central pharmacy. NOSE staff assisted with any logistic problems, and a clinical pharmacist educated any pharmacies that encountered problems ordering, dispensing, or billing for naloxone (Appendix Figure 4). Appendix Figure 2. E-mail template to remind providers about naloxone prescribing. ECW = eClinicalWorks; LCR = lifetime clinical record. Appendix Figure 3. Naloxone for opioid safety patient brochure. Appendix Figure 3. Continued. Appendix Figure 4. Informational sheet for pharmacists on ordering, dispensing, counseling, and billing for naloxone. Data Sources and Data Abstraction Feasibility was assessed through chart reviews of all patients receiving long-term opioid therapy by prescription. Patients receiving sufficient opioids to take at least 1 pill daily for more than 3 months were added to a pain management registry (PMR) by staff at each clinic. This list was downloaded every 3 months during the intervention period, and a merged list of 3138 patients with demographic data was generated in March 2015. A manual chart review was conducted to determine whether patients were valid PMR entrantCs during the study period and to collect the following data: 1) opioid type, dose, quantity per 30 days, and date prescribed at 2 clinic visits (the visit closest to the baseline date [start of naloxone coprescribing at the given clinic or the date the patient was added to the PMR, whichever was later] and the last visit at the clinic before chart review [that is, follow-up date]); 2) the date of initial naloxone prescription; and 3) dates of all ED visits at the county hospital and opioid-relatedness. The ED visits were coded as opioid-related in accordance with documentation for establishing drug-relatedness of ED visits from the Drug Abuse Warning Network (18). Visits were opioid-related if the documenting physician considered them to be primarily due to an adverse event from an opioid or to opioid-seeking behavior; a subset of visits was coded as oversedation if the assessment was an opioid poisoning or other complication attributed by the documenting physician to opioid-induced sedation. Staff reviewing charts included a physician who trained other staff and reviewed uncertain cases; 62.5% of charts were independently assessed by at least 2 reviewers (see Appendix for details). Death information was extracted from the California Electronic Death Record System on 14 July 2015. Feasibility Analysis We assessed bivariate relationships between all demographic and clinical characteristics presented in Table 1 and the receipt of naloxone during the study period using chi-square, Fisher exact (for comparisons with cell sizes <5), and Wilcoxon rank-sum tests. Morphine equivalent daily dose in milligrams (MEQ) was calculated for each patient at baseline and subsequent follow-up dates by using standard conversion ratios from the literature (19, 20). Table 1. Demographic and Clinical Characteristics of PMR Patients, by Receipt of Naloxone Prescription We fit a normal-logistic regression model, with random effects for providers, to assess both patient- and provider-level predictors of naloxone prescription. All baseline patient characteristics assessed in bivariate analyses were included in the model, except for opioid type; the latter was excluded because relevant elements of formulations (such as presence of acetaminophen or duration of action) do not necessarily correspond to opioid type. Only baseline history of any opioid-related ED visit was included in the model because this category of visit was hypothesized to be most relevant to naloxone prescribing. The model also included provider type (attending physician or fellow, resident physician, or other provider) and the size of each providers panel of PMR patients, while controlling for time in days from 1 February 2013 (the earliest program initiation date) to patient baseline date, as well as time between the baseline and follow-up visit dates. To characterize residual differences among providers in naloxone prescription rates, we calculated the odds ratio for the difference between the 25th and 75th percentile values of the random provider effect. A descriptive summary of the PMR panel size, number of patients prescribed naloxone, and percentage of patients prescribed naloxone per provider is presented in Appendix Table 2. Appendix Table 2. Provider-Level Data on Total Number of Patients, Number of Patients Prescribed Naloxone, and Percentage of Patients Prescribed Naloxone Analysis of ED Use In our prespecified plan to assess the association of naloxone receipt with opioid-related ED visits, numbers of opioid-rela

Brief overdose education is sufficient for naloxone distribution to opioid users

BACKGROUND While drug users are frequently equipped with naloxone for lay opioid overdose reversal, the amount of education needed to ensure knowledge of indications and administration is unknown. METHODS We administered four instruments, assessing comfort and knowledge around opioid overdose and naloxone administration, to opioid users receiving naloxone for the first time (N=60) and upon returning for a refill (N=54) at community distribution programs. Participants completed the instruments prior to receiving naloxone; first-time recipients repeated the instruments immediately after the standardized 5-10min education. RESULTS Comfort with recognition of, response to, and administration of naloxone for an overdose event significantly increased after brief education among first-time recipients (p<0.05). Knowledge of appropriate responses to opioid overdose was high across all assessments; 96% of participants could identify at least one acceptable action to assess and one acceptable action to care for an opioid overdose. Facility with naloxone administration was high across all assessments and significantly increased for intranasal administration after education for first-time recipients (p<0.001). First-time recipients (before and after education) and refillers demonstrated a high level of knowledge on the Brief Overdose Recognition and Response Assessment, correctly identifying a mean of 13.7 out of 16 overdose scenarios. CONCLUSIONS Opioid users seeking naloxone in San Francisco have a high level of baseline knowledge around recognizing and responding to opioid overdose and those returning for refills retain that knowledge. Brief education is sufficient to improve comfort and facility in recognizing and managing overdose.

Correlates of overdose risk perception among illicit opioid users

BACKGROUND Opioid-related mortality continues to increase in the United States. The current study assesses demographic and behavioral predictors of perceived overdose risk among individuals who use opioids illicitly. By examining these correlates in the context of established overdose risk factors, we aim to assess whether characteristics and behaviors that have been associated with actual overdose risk translate to higher perception of risk. METHODS We conducted a cross-sectional survey of 172 adult illicit opioid users in San Francisco, CA and used multivariable logistic regression to identify predictors of perception of high risk for opioid overdose. RESULTS Age (aOR=0.96, 95%CI=0.93-1.00) and number of injection days per month (0.91, 0.86-0.97) were associated with a lower odds of perceived high overdose risk. There was no independent association between use of opioid analgesics, concurrent use of opioids and benzodiazepines or cocaine, or HIV status and overdose risk perception. CONCLUSIONS Opioid users who injected more frequently and those who were older were less likely to perceive themselves as being at risk of overdose, notwithstanding that those who inject more are at higher risk of overdose and those who are older are at higher risk overdose mortality. In addition, despite being established overdose risk factors, there was no relationship between use of opioid analgesics, concurrent use of opioids and cocaine or benzodiazepines, or self-reported HIV status and overdose risk perception. These findings highlight key populations of opioid users and established risk factors that may merit focused attention as part of education-based overdose prevention and opioid management strategies.

Novel Interventions to Prevent HIV and HCV Among Persons Who Inject Drugs

Persons who inject drugs (PWID) are at high risk for infection with and poor outcomes from HIV and hepatitis C virus (HCV). Well-established interventions for HIV/HCV prevention among PWID include syringe access, opioid agonist maintenance treatment, and supervised injection facilities, yet these interventions remain unavailable or inadequately resourced in much of the world. We review recent literature on biomedical and behavioral interventions to reduce the burden of HIV/HCV among PWID, with an emphasis on randomized controlled trials and quasi-experimental studies. Since 2013, there have been significant advancements in utilizing antiviral therapy and behavioral interventions for prevention among PWID, including approaches that address the unique needs of couples and sex workers. In addition, there have been significant developments in pharmacotherapies for substance use and the implementation of naloxone for opioid overdose prevention. Notwithstanding multiple ongoing structural challenges in delivering HIV/HCV prevention interventions to PWID, these emerging and rigorously evaluated interventions expand possibilities for prevention among PWID.

Predictors of participant engagement and naloxone utilization in a community-based naloxone distribution program.

AIMS To 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. DESIGN Bivariate 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. SETTING San Francisco, California, USA. PARTICIPANTS Naloxone program participants registered and reversals reported from 2010 to 2013. MEASUREMENTS Baseline characteristics of participants and reported characteristics of reversals. FINDINGS A 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)]. CONCLUSIONS Community 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.

Feasibility, Acceptability, and Tolerability of Targeted Naltrexone for Nondependent Methamphetamine-Using and Binge-Drinking Men Who Have Sex with Men.

Background:There are no effective pharmacologic strategies for nondependent methamphetamine (meth)-using and binge-drinking men who have sex with men (MSM) at high-risk for HIV. We sought to determine the feasibility of enrolling and retaining this population in a pharmacologic trial; the acceptability of pharmacotherapy study procedures; and the tolerability of targeted naltrexone versus placebo. Methods:Thirty meth-using and binge-drinking MSM were randomly assigned 1:1 to 50 mg naltrexone or placebo for 8 weeks for targeted administration (ie, during craving or in anticipation of meth or alcohol use). Substance use counseling and behavioral assessments were conducted every 2 weeks. Medication use was measured using WisePill dispensers. Results:Trial completion was 93%; visit completion rate was 95%. Mean weekly number of medication pills taken was 2.1 and was similar between arms. Participant satisfaction rate was 96%. There were neither serious adverse events nor differences in adverse event rates between arms. In exploratory intention-to-treat analyses, there were no differences in meth use and drinking. Naltrexone participants had greater reductions in serodiscordant receptive anal intercourse [incident rate ratio (IRR) = 0.15; 95% CI = 0.05 to 0.42] and serodiscordant condomless receptive anal intercourse (IRR = 0.11; 95% CI = 0.03 to 0.37), compared with placebo. In subgroup analyses among frequent meth users, naltrexone participants had greater reductions in meth-using days (IRR = 0.78; 95% CI = 0.62 to 0.99). In as-treated analyses, frequent study medication users in the naltrexone arm had greater reductions in binge drinking days (IRR = 0.72; 95% CI = 0.54 to 0.97). Conclusions:Targeted naltrexone is a feasible, acceptable, and tolerable intervention strategy for nondependent meth-using and binge-drinking MSM. Naltrexone was associated with significant sexual risk reductions; and for some individuals, naltrexone was associated with meth and binge-drinking reductions.

Residential proximity to organophosphate and carbamate pesticide use during pregnancy, poverty during childhood, and cognitive functioning in 10-year-old children

BACKGROUND Low-income communities and communities of color have been shown to experience disproportionate exposure to agricultural pesticides, which have been linked to poorer neurobehavioral outcomes in infants and children. Few studies have assessed health impacts of pesticide mixtures in the context of socioeconomic adversity. OBJECTIVES To examine associations between residential proximity to toxicity-weighted organophosphate (OP) and carbamate pesticide use during pregnancy, household- and neighborhood-level poverty during childhood, and IQ scores in 10-year-old children. METHODS We evaluated associations between both nearby agricultural pesticide use and poverty measures and cognitive abilities in 10-year-old children (n = 501) using data from a longitudinal birth cohort study linked with data from the California Pesticide Use Reporting system and the American Community Survey. Associations were assessed using multivariable linear regression. RESULTS Children of mothers in the highest quartile compared to the lowest quartile of proximal pesticide use had lower performance on Full Scale IQ [β = -3.0; 95% Confidence Interval (CI) = (-5.6, -0.3)], Perceptual Reasoning [β = -4.0; (-7.6, -0.4)], and Working Memory [β = -2.8; (-5.6, -0.1)]. Belonging to a household earning an income at or below the poverty threshold was associated with approximately two point lower scores on Full Scale IQ, Verbal Comprehension, and Working Memory. Living in the highest quartile of neighborhood poverty at age 10 was associated with approximately four point lower performance on Full Scale IQ, Verbal Comprehension, Perceptual Reasoning, and Working memory. CONCLUSIONS Residential proximity to OP and carbamate pesticide use during pregnancy and both household- and neighborhood-level poverty during childhood were independently associated with poorer cognitive functioning in children at 10 years of age.

Binge drinking concurrent with anal intercourse and condom use among men who have sex with men

ABSTRACT 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.

Performance Measures of Diagnostic Codes for Detecting Opioid Overdose in the Emergency Department

OBJECTIVES Opioid overdose mortality has tripled in the United States since 2000 and opioids are responsible for more than half of all drug overdose deaths, which reached an all-time high in 2014. Opioid overdoses resulting in death, however, represent only a small fraction of all opioid overdose events and efforts to improve surveillance of this public health problem should include tracking nonfatal overdose events. International Classification of Disease (ICD) diagnosis codes, increasingly used for the surveillance of nonfatal drug overdose events, have not been rigorously assessed for validity in capturing overdose events. The present study aimed to validate the use of ICD, 9th revision, Clinical Modification (ICD-9-CM) codes in identifying opioid overdose events in the emergency department (ED) by examining multiple performance measures, including sensitivity and specificity. METHODS Data on ED visits from January 1, 2012, to December 31, 2014, including clinical determination of whether the visit constituted an opioid overdose event, were abstracted from electronic medical records for patients prescribed long-term opioids for pain from any of six safety net primary care clinics in San Francisco, California. Combinations of ICD-9-CM codes were validated in the detection of overdose events as determined by medical chart review. Both sensitivity and specificity of different combinations of ICD-9-CM codes were calculated. Unadjusted logistic regression models with robust standard errors and accounting for clustering by patient were used to explore whether overdose ED visits with certain characteristics were more or less likely to be assigned an opioid poisoning ICD-9-CM code by the documenting physician. RESULTS Forty-four (1.4%) of 3,203 ED visits among 804 patients were determined to be opioid overdose events. Opioid-poisoning ICD-9-CM codes (E850.2-E850.2, 965.00-965.09) identified overdose ED visits with a sensitivity of 25.0% (95% confidence interval [CI] = 13.6% to 37.8%) and specificity of 99.9% (95% CI = 99.8% to 100.0%). Expanding the ICD-9-CM codes to include both nonspecified and general (i.e., without a decimal modifier) drug poisoning and drug abuse codes identified overdose ED visits with a sensitivity of 56.8% (95% CI = 43.6%-72.7%) and specificity of 96.2% (95% CI = 94.8%-97.2%). Additional ICD-9-CM codes not explicitly relevant to opioid overdose were necessary to further enhance sensitivity. Among the 44 overdose ED visits, neither naloxone administration during the visit, whether the patient responded to the naloxone, nor the specific opioids involved were associated with the assignment of an opioid poisoning ICD-9-CM code (p ≥ 0.05). CONCLUSIONS Tracking opioid overdose ED visits by diagnostic coding is fairly specific but insensitive, and coding was not influenced by administration of naloxone or the specific opioids involved. The reason for the high rate of missed cases is uncertain, although these results suggest that a more clearly defined case definition for overdose may be necessary to ensure effective opioid overdose surveillance. Changes in coding practices under ICD-10 might help to address these deficiencies.