Methodological approaches for the prediction of opioid use-related epidemics in the United States: a narrative review and cross-disciplinary call to action.

The opioid crisis in the United States has been defined by waves of drug- and locality-specific Opioid use-Related Epidemics (OREs) of overdose and bloodborne infections, among a range of health harms. The ability to identify localities at risk of such OREs, and better yet, to predict which ones will experience them, holds the potential to mitigate further morbidity and mortality. This narrative review was conducted to identify and describe quantitative approaches aimed at the "risk assessment," "detection" or "prediction" of OREs in the United States. We implemented a PubMed search composed of the: (1) objective (eg, prediction), (2) epidemiologic outcome (eg, outbreak), (3) underlying cause (ie, opioid use), (4) health outcome (eg, overdose, HIV), (5) location (ie, US). In total, 46 studies were included, and the following information extracted: discipline, objective, health outcome, drug/substance type, geographic region/unit of analysis, and data sources. Studies identified relied on clinical, epidemiological, behavioral and drug markets surveillance and applied a range of methods including statistical regression, geospatial analyses, dynamic modeling, phylogenetic analyses and machine learning. Studies for the prediction of overdose mortality at national/state/county and zip code level are rapidly emerging. Geospatial methods are increasingly used to identify hotspots of opioid use and overdose. In the context of infectious disease OREs, routine genetic sequencing of patient samples to identify growing transmission clusters via phylogenetic methods could increase early detection capacity. A coordinated implementation of multiple, complementary approaches would increase our ability to successfully anticipate outbreak risk and respond preemptively. We present a multi-disciplinary framework for the prediction of OREs in the US and reflect on challenges research teams will face in implementing such strategies along with good practices.

Frequency of health-care utilization by adults who use illicit drugs: a systematic review and meta-analysis.

AIMS: To summarize evidence on the frequency and predictors of health-care utilization among people who use illicit drugs. DESIGN: Systematic search of MEDLINE, EMBASE and PsychINFO for observational studies reporting health-care utilization published between 1 January 2000 and 3 December 2018. We conducted narrative synthesis and meta-analysis following a registered protocol (identifier: CRD42017076525). SETTING AND PARTICIPANTS: People who use heroin, powder cocaine, crack cocaine, methamphetamine, amphetamine, ecstasy/3,4-methyl​enedioxy​methamphetamine (MDMA), cannabis, hallucinogens or novel psychoactive substances; have a diagnosis of 'substance use disorder'; or use drug treatment services. MEASUREMENTS: Primary outcomes were the cumulative incidence (risk) and rate of care episodes in three settings: primary care, hospital admissions (in-patient) and emergency department (ED). FINDINGS: Ninety-two studies were included, 84% from North America and Australia. Most studies focused on people using heroin, methamphetamine or crack cocaine, or who had a diagnosis of drug dependence. We were able to conduct a meta-analysis of rates across 25 studies reporting ED episodes and 25 reporting hospital admissions, finding pooled rates of 151 [95% confidence interval (CI) = 114-201] and 41 (95% CI = 30-57) per 100 person-years, respectively; on average 4.8 and 7.1 times more often than the general population. Heterogeneity was very high and was not explained by drugs used, country of study, recruitment setting or demographic characteristics. Predictors of health-care utilization were consistent across studies and included unstable housing, drug injection and mental health problems. Opioid substitution therapy was consistently associated with reduced ED presentation and hospital admission. There was minimal research on health-care utilization by people using ecstasy/MDMA, powder cocaine, hallucinogens or novel psychoactive substances. CONCLUSIONS: People who use illicit drugs are admitted to emergency department or hospital several times more often than the general population.

Fentanyl test strips as an opioid overdose prevention strategy: Findings from a syringe services program in the Southeastern United States.

BACKGROUND: In 2016, the number of overdose deaths involving illicitly-manufactured fentanyl (IMF) surpassed heroin and prescription opioid deaths in the United States for the first time, with IMF-involved overdose deaths increasing more than 500% across 10 states from 2013 to 2016. IMF is an extremely potent synthetic opioid that is regularly mixed with heroin and often sold to unwitting consumers. Community-based organizations have started to distribute fentanyl test strips (FTS) as a strategy to identify IMF in street purchased products. We investigated the association between FTS use and changes in drug use behavior and perceived overdose safety among a community-based sample of people who inject drugs (PWID) in the United States. METHODS: Between September-October 2017, a total of 125 PWID completed an online survey about their most recent FTS use in Greensboro, North Carolina. Our first outcome of interest included whether PWID engaged in any of the following changes in drug use behavior after using FTS: used less than usual, administered tester shot, pushed syringe plunger slower than usual, and snorted instead of injected. Our second outcome of interest was whether PWID felt that FTS use made them feel better able to protect themselves from overdose. We conducted bivariate and multivariate analyses to determine the association between FTS use and these two outcomes. RESULTS: Overall, 63% of the sample reported a positive FTS test result and 81% reported using FTS prior to consuming their drugs. For the outcomes, 43% reported a change in drug use behavior and 77% indicated increased perceived overdose safety by using FTS. In multivariable models adjusting for demographic and FTS correlates, PWID with a positive FTS test result had five times the odds of reporting changes in drug use behavior compared to those with a negative result. PWID who used the FTS after drug consumption were 70% less likely to report behavioral changes at subsequent drug consumption compared to those who used it before consumption. PWID who were not existing clients of the syringe services program had four times higher odds than existing clients to report increased overdose safety from using FTS. CONCLUSIONS: We found that using FTS and receiving a positive test result was associated with changes in drug use behavior and perceptions of overdose safety. FTS may represent an effective addition to current overdose prevention efforts when included with other evidence-based strategies to prevent opioid overdose and related harm.

Drawing attention to a neglected injecting-related harm: a systematic review of AA amyloidosis among people who inject drugs.

BACKGROUND AND AIMS: Chronic skin and soft tissue infections (SSTI) among people who inject drugs (PWID) can lead to AA amyloidosis: a serious, yet neglected, multi-organ disease. We aim to synthesize findings on the epidemiology, risk factors, clinical outcomes, screening recommendations and challenges to treatment for AA amyloidosis among PWID. METHODS: A systematic review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). We searched the following bibliographic databases in July 2017: CINAHL Plus, Embase, Global Health, MEDLINE, PsycEXTRA, PsycINFO and SCOPUS. Studies were included if they investigated AA amyloidosis in PWID. Studies were not restricted to location, study type, year or language of publication. Study heterogeneity precluded meta-analysis; we present a narrative review of the literature. RESULTS: Thirty-seven papers from eight countries met inclusion criteria. A total of 781 PWID are reported on, of whom 177 had AA amyloidosis. Where disease causality is established, it is attributed to chronic inflammation caused by injecting-related SSTIs. Most (88.7%) PWID with AA amyloidosis had SSTIs. The proportion of PWID with AA amyloidosis at post-mortem ranged from 1.6% (Germany) to 22.5% (Serbia). Biopsy studies reported from 5.26% (Portugal) to 50% (Germany) of AA amyloidosis in PWID with suspected or known kidney disease. Following diagnosis, the typical trajectory for PWID with AA amyloidosis was rapid deterioration of renal function requiring haemodialysis. Treatment difficulties, end-stage renal failure and premature death from sepsis were observed. Good outcomes, including reversibility of AA amyloidosis, are attributed to rapid treatment of the underlining inflammation and injecting cessation. Notably, given the population in question, no studies were published in addiction or harm reduction journals; most (92%) appeared in specialist nephrology and medical journals. CONCLUSION: There is strong evidence of an association between skin and soft tissue infections (SSTIs) and AA amyloidosis. Among people who inject drugs, injecting-related SSTIs are a significant cause of morbidity and premature mortality and there is evidence of increasing SSTI prevalence. Limitations in the literature make it difficult to estimate AA amyloidosis prevalence among people who inject drugs.

Reinterpreting ethnic patterns among white and African American men who inject heroin: a social science of medicine approach.

BACKGROUND: Street-based heroin injectors represent an especially vulnerable population group subject to negative health outcomes and social stigma. Effective clinical treatment and public health intervention for this population requires an understanding of their cultural environment and experiences. Social science theory and methods offer tools to understand the reasons for economic and ethnic disparities that cause individual suffering and stress at the institutional level. METHODS AND FINDINGS: We used a cross-methodological approach that incorporated quantitative, clinical, and ethnographic data collected by two contemporaneous long-term San Francisco studies, one epidemiological and one ethnographic, to explore the impact of ethnicity on street-based heroin-injecting men 45 years of age or older who were self-identified as either African American or white. We triangulated our ethnographic findings by statistically examining 14 relevant epidemiological variables stratified by median age and ethnicity. We observed significant differences in social practices between self-identified African Americans and whites in our ethnographic social network sample with respect to patterns of (1) drug consumption; (2) income generation; (3) social and institutional relationships; and (4) personal health and hygiene. African Americans and whites tended to experience different structural relationships to their shared condition of addiction and poverty. Specifically, this generation of San Francisco injectors grew up as the children of poor rural to urban immigrants in an era (the late 1960s through 1970s) when industrial jobs disappeared and heroin became fashionable. This was also when violent segregated inner city youth gangs proliferated and the federal government initiated its "War on Drugs." African Americans had earlier and more negative contact with law enforcement but maintained long-term ties with their extended families. Most of the whites were expelled from their families when they began engaging in drug-related crime. These historical-structural conditions generated distinct presentations of self. Whites styled themselves as outcasts, defeated by addiction. They professed to be injecting heroin to stave off "dopesickness" rather than to seek pleasure. African Americans, in contrast, cast their physical addiction as an oppositional pursuit of autonomy and pleasure. They considered themselves to be professional outlaws and rejected any appearance of abjection. Many, but not all, of these ethnographic findings were corroborated by our epidemiological data, highlighting the variability of behaviors within ethnic categories. CONCLUSIONS: Bringing quantitative and qualitative methodologies and perspectives into a collaborative dialog among cross-disciplinary researchers highlights the fact that clinical practice must go beyond simple racial or cultural categories. A clinical social science approach provides insights into how sociocultural processes are mediated by historically rooted and institutionally enforced power relations. Recognizing the logical underpinnings of ethnically specific behavioral patterns of street-based injectors is the foundation for cultural competence and for successful clinical relationships. It reduces the risk of suboptimal medical care for an exceptionally vulnerable and challenging patient population. Social science approaches can also help explain larger-scale patterns of health disparities; inform new approaches to structural and institutional-level public health initiatives; and enable clinicians to take more leadership in changing public policies that have negative health consequences.

The good-enough science-and-politics of anthropological collaboration with evidence-based clinical research: Four ethnographic case studies.

The apolitical legitimacy of "evidence-based medicine" offers a practical means for ethnography and critical social-science-and-humanities-of-health theory to transfer survival resources to structurally vulnerable populations and to engage policy and services audiences with urgent political problems imposed on the urban poor in the United States that harm health: most notably, homelessness, hyperincarceration, social service cut-backs and the War on Drugs. We present four examples of collaborations between ethnography and clinical research projects that demonstrate the potentials and limits of promoting institutional reform, political debate and action through distinct strategies of cross-methodological dialog with epidemiological and clinical services research. Ethnographic methods alone, however, are simply a technocratic add-on. They must be informed by critical theory to contribute effectively and transformatively to applied health initiatives. Ironically, technocratic, neoliberal logics of cost-effectiveness can sometimes render radical service and policy reform initiatives institutionally credible, fundable and capable of generating wider political support, even though the rhetoric of economic efficacy is a double-edged sword. To extend the impact of ethnography and interdisciplinary theories of political-economic, cultural and disciplinary power relations into applied clinical and public health research, anthropologists - and their fellow travelers - have to be able to strategically, but respectfully learn to see through the positivist logics of clinical services research as well as epidemiological epistemology in order to help clinicians achieve - and extend - their applied priorities. In retrospect, these four very differently-structured collaborations suggest the potential for "good-enough" humble scientific and political strategies to work for, and with, structurally vulnerable populations in a punitive neoliberal era of rising social inequality, cutbacks of survival services, and hyperincarceration of the poor.

Naloxone distribution and cardiopulmonary resuscitation training for injection drug users to prevent heroin overdose death: a pilot intervention study.

Fatal heroin overdose has become a leading cause of death among injection drug users (IDUs). Several recent feasibility studies have concluded that naloxone distribution programs for heroin injectors should be implemented to decrease heroin over-dose deaths, but there have been no prospective trials of such programs in North America. This pilot study was undertaken to investigate the safety and feasibility of training injection drug using partners to perform cardiopulmonary resuscitation (CPR) and administer naloxone in the event of heroin overdose. During May and June 2001, 24 IDUs (12 pairs of injection partners) were recruited from street settings in San Francisco. Participants took part in 8-hour training in heroin overdose prevention, CPR, and the use of naloxone. Following the intervention, participants were prospectively followed for 6 months to determine the number and outcomes of witnessed heroin overdoses, outcomes of participant interventions, and changes in participants' knowledge of overdose and drug use behavior. Study participants witnessed 20 heroin overdose events during 6 months follow-up. They performed CPR in 16 (80%) events, administered naloxone in 15 (75%) and did one or the other in 19 (95%). All overdose victims survived. Knowledge about heroin overdose management increased, whereas heroin use decreased. IDUs can be trained to respond to heroin overdose emergencies by performing CPR and administering naloxone. Future research is needed to evaluate the effectiveness of this peer intervention to prevent fatal heroin overdose.

Attitudes about prescribing take-home naloxone to injection drug users for the management of heroin overdose: a survey of street-recruited injectors in the San Francisco Bay Area.

Naloxone, an injectable opiate antagonist, can immediately reverse an opiate overdose and prevent overdose death. We sought to determine injection drug users' (IDUs) attitudes about being prescribed take-home naloxone. During November 1999 to February 2000, we surveyed 82 street-recruited IDUs from the San Francisco Bay Area of California who had experienced one or more heroin overdose events. We used a questionnaire that included structured and open-ended questions. Most respondents (89%) had witnessed an overdose, and 90% reported initially attempting lay remedies in an effort to help companions survive. Only 51% reported soliciting emergency assistance (calling 911) for the last witnessed overdose, with most hesitating due to fear of police involvement. Of IDUs surveyed, 87% were strongly in favor of participating in an overdose management training program to receive take-home naloxone and training in resuscitation techniques. Nevertheless, respondents expressed a variety of concerning attitudes. If provided naloxone, 35% predicted that they might feel comfortable using greater amounts of heroin, 62% might be less inclined to call 911 for an overdose, 30% might leave an overdose victim after naloxone resuscitation, and 46% might not be able to dissuade the victim from using heroin again to alleviate withdrawal symptoms induced by naloxone. Prescribing take-home naloxone to IDUs with training in its use and in resuscitation techniques may represent a life-saving, peer-based adjunct to accessing emergency services. Nevertheless, strategies for overcoming potential risks associated with the use of take-home naloxone would need to be emphasized in an overdose management training program.