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      Fatal overdose prevention and experience with naloxone: A cross-sectional study from a community-based cohort of people who inject drugs in Baltimore, Maryland

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          Abstract

          Introduction

          Overdose is a leading cause of death in the United States, especially among people who inject drugs (PWID). Improving naloxone access and carrying among PWID may offset recent increases in overdose mortality associated with the influx of synthetic opioids in the drug market. This study characterized prevalence and correlates of several naloxone outcomes among PWID.

          Methods

          During 2018, a survey to assess experience with naloxone was administered to 915 participants in the AIDS Linked to the IntraVenous Experience (ALIVE) study, an ongoing community-based observational cohort of people who currently inject or formerly injected drugs in Baltimore, Maryland. We examined the associations of naloxone outcomes (training, supply, use, and regular possession) with socio-demographic, substance use and healthcare utilization factors among PWID in order to characterize gaps in naloxone implementation among this high-risk population.

          Results

          Median age was 56 years, 34% were female, 85% were African American, and 31% recently injected. In the past six months, 46% (n = 421) reported receiving training in overdose prevention, 38% (n = 346) had received a supply of naloxone, 9% (n = 85) had administered naloxone, and 9% (n = 82) reported usually carrying a supply of naloxone. Recent non-fatal overdose was not associated with any naloxone outcomes in adjusted analysis. Active opioid use (aOR = 2.10, 95% CI: 1.03, 4.28) and recent treatment of alcohol or substance use disorder (aOR = 2.01, 95% CI: 1.13, 3.56) were associated with regularly carrying naloxone.

          Conclusion

          Further work is needed to encourage PWID to carry and effectively use naloxone to decrease rates of fatal opioid overdose. While accessing treatment for substance use disorder was positively associated with carrying naloxone, EMS response to 911 calls for overdose, the emergency department, and syringe services programs may be settings in which naloxone access and carrying could be encouraged among PWID.

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          Most cited references30

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          Global burden of disease attributable to illicit drug use and dependence: findings from the Global Burden of Disease Study 2010.

          No systematic attempts have been made to estimate the global and regional prevalence of amphetamine, cannabis, cocaine, and opioid dependence, and quantify their burden. We aimed to assess the prevalence and burden of drug dependence, as measured in years of life lived with disability (YLDs), years of life lost (YLLs), and disability-adjusted life years (DALYs). We conducted systematic reviews of the epidemiology of drug dependence, and analysed results with Global Burden of Diseases, Injuries, and Risk Factors Study 2010 (GBD 2010) Bayesian meta-regression technique (DisMod-MR) to estimate population-level prevalence of dependence and use. GBD 2010 calculated new disability weights by use of representative community surveys and an internet-based survey. We combined estimates of dependence with disability weights to calculate prevalent YLDs, YLLs, and DALYs, and estimated YLDs, YLLs, and DALYs attributable to drug use as a risk factor for other health outcomes. Illicit drug dependence directly accounted for 20·0 million DALYs (95% UI 15·3-25·4 million) in 2010, accounting for 0·8% (0·6-1·0) of global all-cause DALYs. Worldwide, more people were dependent on opioids and amphetamines than other drugs. Opioid dependence was the largest contributor to the direct burden of DALYs (9·2 million, 95% UI 7·1-11·4). The proportion of all-cause DALYs attributed to drug dependence was 20 times higher in some regions than others, with an increased proportion of burden in countries with the highest incomes. Injecting drug use as a risk factor for HIV accounted for 2·1 million DALYs (95% UI 1·1-3·6 million) and as a risk factor for hepatitis C accounted for 502,000 DALYs (286,000-891,000). Suicide as a risk of amphetamine dependence accounted for 854,000 DALYs (291,000-1,791,000), as a risk of opioid dependence for 671,000 DALYs (329,000-1,730,000), and as a risk of cocaine dependence for 324,000 DALYs (109,000-682,000). Countries with the highest rate of burden (>650 DALYs per 100,000 population) included the USA, UK, Russia, and Australia. Illicit drug use is an important contributor to the global burden of disease. Efficient strategies to reduce disease burden of opioid dependence and injecting drug use, such as delivery of opioid substitution treatment and needle and syringe programmes, are needed to reduce this burden at a population scale. Australian National Health and Medical Research Council, Australian Government Department of Health and Ageing, Bill & Melinda Gates Foundation. Copyright © 2013 Elsevier Ltd. All rights reserved.
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            Opioid Overdose Prevention Programs Providing Naloxone to Laypersons — United States, 2014

            Drug overdose deaths in the United States have more than doubled since 1999 (1). During 2013, 43,982 drug overdose deaths (unintentional, intentional [suicide or homicide], or undetermined intent) were reported (1). Among these, 16,235 (37%) were associated with prescription opioid analgesics (e.g., oxycodone and hydrocodone) and 8,257 (19%) with heroin (2). For many years, community-based programs have offered opioid overdose prevention services to laypersons who might witness an overdose, including persons who use drugs, their families and friends, and service providers. Since 1996, an increasing number of programs provide laypersons with training and kits containing the opioid antagonist naloxone hydrochloride (naloxone) to reverse the potentially fatal respiratory depression caused by heroin and other opioids (3). In July 2014, the Harm Reduction Coalition (HRC), a national advocacy and capacity-building organization, surveyed 140 managers of organizations in the United States known to provide naloxone kits to laypersons. Managers at 136 organizations completed the survey, reporting on the amount of naloxone distributed, overdose reversals by bystanders, and other program data for 644 sites that were providing nalox-one kits to laypersons as of June 2014. From 1996 through June 2014, surveyed organizations provided naloxone kits to 152,283 laypersons and received reports of 26,463 overdose reversals. Providing opioid overdose training and naloxone kits to laypersons who might witness an opioid overdose can help reduce opioid overdose mortality. Since 2008, HRC has maintained a database of organizations providing naloxone kits to laypersons. The Opioid Safety and Naloxone Network is a national network of naloxone experts, program administrators, and advocates. Before the survey, HRC staff polled network participants for information on any new organizations providing naloxone kits to laypersons that should be included in the survey. In July 2014, HRC e-mailed a link to an online survey to managers of 140 organizations known to provide naloxone kits to laypersons. These organizations included public health departments, pharmacies, health care facilities, substance use treatment facilities, and community-based organizations providing services to persons who use drugs, including current or former opioid (heroin or pharmaceutical) users, and other potential witnesses to overdoses. Law enforcement organizations, emergency medical services, and other professional first responders using naloxone were not included in this survey. The survey included questions about the year the organization began operating; the numbers of sites or local programs providing naloxone kits; the number of persons trained in overdose prevention and provided naloxone kits; and the number of reports of overdose reversals (administration of naloxone by a trained layperson in the event of an overdose) (4), as well as whether the reports were based on program data or were estimates. The survey also asked about the naloxone formulations currently provided in kits, models for training and providing naloxone kits, funding sources, and any difficulties obtaining naloxone. To obtain data for a recent full calendar year, organizations providing naloxone kits during calendar year 2013 were asked to provide specific data for that year, including numbers of persons provided naloxone kits, reversals reported, and naloxone vials provided; characteristics of persons who received naloxone kits (e.g., persons who use drugs, friends and family members, service providers); characteristics of persons reporting overdose reversals; and the drugs involved in reported overdose reversals. HRC staff used follow-up e-mails and telephone calls to encourage participation and clarify responses. Managers from 136 (97.1%) organizations completed the survey, including those from 84 community-based organizations, 18 health care facilities, 10 Veterans Administration health care systems, 18 state or local health departments, and six pharmacies. Half of the responding organizations began operating during January 2013–June 2014 (Figure 1). Respondents provided reports for 644 local opioid overdose prevention sites that provide naloxone kits, located in 30 states and the District of Columbia (DC) (Figure 2). Thirty-eight respondents provided consolidated data for multiple local sites providing naloxone kits. Some organizations estimated responses; for example, one health department estimated the number of laypersons receiving naloxone kits on the basis of the number of kits distributed to local sites. Three state health departments (Massachusetts, New Mexico, and New York) oversee operations of statewide naloxone programs, with 334 local sites (51.9% of the 644 local sites). From 1996, when the first organization began providing naloxone, through June 2014, the 136 responding organizations reported providing training and naloxone kits to 152,283 laypersons (range = 1–36,450; median = 100; mean = 1,120).* The 109 organizations that collect reports of reversals documented 26,463 overdose reversals (range = 0–5,430; median = 9; mean = 243).† During 2013, 93 organizations reported distributing or prescribing naloxone to 37,920 laypersons (range = 0–9,000; median = 75; mean = 407.7).§ The 68 (50%) organizations that collect reports of reversals documented 8,032 overdose reversals (range = 0–2,079; median = 10; mean = 118.1).¶ Ninety-three organizations collected information on the characteristics of laypersons who were provided naloxone kits. Laypersons who received naloxone kits were characterized as persons who use drugs (81.6%); friends and family members (11.7%); service providers (3.3%); or unknown (3.4%).** Sixty-eight organizations provided information about lay-persons who reported administering naloxone, characterizing them as persons who use drugs (82.8%); friends and family members (9.6%); service providers (0.2%); or unknown (7.4%).†† Forty-two organizations collected information from laypersons about the drugs that appeared to be involved in the reversed overdoses; heroin was involved in 81.6% and prescription opioids in 14.1%.§§ Various program models were used by organizations to provide naloxone to laypersons, including distribution of naloxone kits by trained nonmedical staff or volunteers under a standing order (60 [44.1%]), by medical staff (49 [36.0%]), prescriptions written by a medical provider and filled at a pharmacy (39 [28.7%]), pharmacists dispensing directly via collaborative practice agreements and other mechanisms (12 [8.8%]), and other protocols (19 [14.0%]). Thirty-three organizations used more than one model. During 2013, 90 (66.2%) of the 136 organizations reported distributing 140,053 naloxone vials, including refills (range = 1–53,200; median = 179.5; mean = 1,556.1).¶¶ Three respondents whose organizations were operational in 2013 did not report on the number of vials because they furnished prescriptions to be filled at a pharmacy. The remaining 43 organizations indicated that they were not yet providing naloxone kits during 2013. Sixty-nine respondents (50.7%) reported their organization provided only injectable naloxone, 51 (37.5%) provided only intranasal naloxone, and 16 (11.8%) provided both injectable and intranasal naloxone.*** A total of 111,602 vials (79.7%) of injectable naloxone (21.4% 10 mL and 58.1% 1 mL) and 28,446 (20.3%) vials of intranasal naloxone were provided to laypersons. Organizations were characterized as small, medium, large, or very large, on the basis of the number of naloxone vials distributed during 2013. The 11 large and very large organizations provided naloxone to 28,604 laypersons, representing 75.4% of all 2013 recipients (Table). Forty (29.4%) organizations reported difficulties maintaining an adequate supply of naloxone, and 73 (53.7%) reported inadequate resources to sustain or expand their organization’s efforts to disseminate naloxone kits. Discussion Organizations that provide naloxone kits to laypersons have expanded substantially since a similar survey in 2010 (5), reflecting a 183% (from 48 to 136) increase in the number of responding organizations; a 243% (from 188 to 644) increase in the number of local sites providing naloxone; a 187% (from 53,032 to 152,283) increase in the number of laypersons provided naloxone kits; a 160% (from 10,171 to 26,463) increase in the number of reversals reported; and a 94% (from 16 to 30) increase in states (including DC) with at least one organization providing naloxone. Half of the responding organizations began operating during January 2013–June 2014. Although early adopters of naloxone kit provision were mainly syringe exchanges, other programs, including substance use treatment facilities, Veterans Administration health care systems, primary care clinics, and pharmacies have started providing naloxone to laypersons. Providing naloxone kits to laypersons reduces overdose deaths (4), is safe (3), and is cost-effective (6). U.S. and international health organizations recommend providing naloxone kits to laypersons who might witness an opioid overdose (3,7); to patients in substance use treatment programs (3,7,8); to persons leaving prison and jail (3,7,8); and as a component of responsible opioid prescribing (8). Although the number of organizations providing naloxone kits to laypersons is increasing, in 2013, 20 states had no such organization, and nine had less than one layperson per 100,000 population who had received a naloxone kit. Among these 29 states with minimal or no access to naloxone kits for laypersons, 11 had age-adjusted 2013 drug overdose death rates higher than the national median (2). Some organizations reported information on the laypersons receiving naloxone kits (N = 99 organizations), using naloxone in overdose reversals (N = 68), and the drugs that appeared to have caused the overdose (N = 42). Persons who use drugs accounted for 81.6% of laypersons who received naloxone kits; they also performed the majority (82.8%) of reported overdose reversals. A majority (81.6%) of the overdoses that were reversed involved heroin, indicating that organizations are reaching laypersons who witness heroin overdoses. A study of a community-based naloxone program in San Francisco also found that persons who use drugs play a major role in reversing heroin overdoses (9). Additional interventions are needed to reach persons who may witness prescription opioid analgesic overdoses, which account for nearly twice as many deaths as heroin overdoses. Forty (29.4%) respondents reported that their organization has experienced problems obtaining naloxone. Prices of intranasal naloxone more than doubled in the second half of 2014 (10) and Opioid Safety and Naloxone Network members report that cost increases are reducing the quantity of naloxone purchased and provided to laypersons (Matt Curtis, VOCAL NY, personal communication, 2015). The findings in this report are subject to at least four limitations. First, despite extensive knowledge of naloxone distribution programs by the Harm Reduction Coalition and Opioid Safety and Naloxone Network, organizations providing naloxone kits are increasing rapidly and some might not yet be known to HRC and therefore, might not be included in the survey, which may underestimate the impact of these programs. Second, survey responses are based on unconfirmed reports from organizations providing naloxone kits. Third, some reports provided by organizations are based on estimates. These three limitations could result in either under or over-reporting of persons provided naloxone kits. Finally, the numbers of overdose reversals likely were under-reported, because some sites, such as pharmacies, do not collect reversal reports. Organizations providing naloxone kits to laypersons receive many reports of overdose reversals and can reach large numbers of potential overdose bystanders. Comprehensive prevention measures that include teaching laypersons how to respond to overdoses and administer naloxone might help prevent opioid drug overdose deaths. This report suggests that many programs reach persons who witness heroin-related overdoses; additional methods are needed to provide naloxone kits to persons who might witness prescription opioid analgesic overdoses. Summary What is already known on this topic? Drug overdose deaths in the United States have more than doubled since 1999, reaching a total of 43,982 in 2013. Heroin and prescription opioids are major causes of drug overdose deaths. Naloxone is the standard medication used for reversal of the potentially fatal respiratory depression caused by opioid overdose. What is added by this report? From 1996 through June 2014, a total of 644 local sites in 30 states and the District of Columbia reported providing naloxone kits to 152,283 laypersons and receiving reports of 26,463 drug overdose reversals using naloxone from 1996 through June 2014. Most laypersons who reported using the kits to reverse an overdose were persons who use drugs, and many of the reported reversals involved heroin overdoses. Medical clinics and pharmacies have started providing naloxone kits to laypersons, and the reported number of organizations providing kits almost doubled from January 2013 through June 2014. What are the implications for public health practice? Organizations training and providing naloxone kits to laypersons can reach large numbers of potential overdose witnesses and result in many reported overdose reversals. Comprehensive prevention measures that include teaching laypersons how to respond to overdoses and administer naloxone prevent opioid-related drug overdose deaths. Additional methods are needed to provide naloxone kits to persons who might witness prescription opioid analgesic overdoses.
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              Naloxone distribution and cardiopulmonary resuscitation training for injection drug users to prevent heroin overdose death: a pilot intervention study.

              K Seal (2005)
              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.
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                Author and article information

                Contributors
                Role: ConceptualizationRole: Formal analysisRole: MethodologyRole: Writing – original draftRole: Writing – review & editing
                Role: Formal analysisRole: Writing – original draftRole: Writing – review & editing
                Role: Data curationRole: Formal analysisRole: MethodologyRole: Writing – review & editing
                Role: Funding acquisitionRole: SupervisionRole: Writing – review & editing
                Role: ConceptualizationRole: Funding acquisitionRole: SupervisionRole: Writing – review & editing
                Role: ConceptualizationRole: Formal analysisRole: Funding acquisitionRole: MethodologyRole: SupervisionRole: Writing – original draftRole: Writing – review & editing
                Role: Editor
                Journal
                PLoS One
                PLoS ONE
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, CA USA )
                1932-6203
                11 March 2020
                2020
                : 15
                : 3
                : e0230127
                Affiliations
                [1 ] Division of Addiction Medicine, Johns Hopkins School of Medicine, Baltimore, Maryland, United States of America
                [2 ] Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, United States of America
                [3 ] Division of Infectious Diseases, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States of America
                University of California San Diego School of Medicine, UNITED STATES
                Author notes

                Competing Interests: The authors have declared that no competing interests exist.

                Author information
                http://orcid.org/0000-0002-7022-6385
                http://orcid.org/0000-0002-9450-5311
                Article
                PONE-D-19-16951
                10.1371/journal.pone.0230127
                7065783
                32160244
                43c1f6e3-d3eb-4cc2-859f-c546f52c0a4f
                © 2020 Buresh et al

                This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                : 14 June 2019
                : 22 February 2020
                Page count
                Figures: 0, Tables: 3, Pages: 13
                Funding
                Funded by: funder-id http://dx.doi.org/10.13039/100000026, National Institute on Drug Abuse;
                Award ID: U01-DA-036297
                Award Recipient :
                Funded by: funder-id http://dx.doi.org/10.13039/100000026, National Institute on Drug Abuse;
                Award ID: R01-DA-12568
                Award Recipient :
                Funded by: funder-id http://dx.doi.org/10.13039/100000060, National Institute of Allergy and Infectious Diseases;
                Award ID: T32-AI102623
                Award Recipient :
                Funded by: funder-id http://dx.doi.org/10.13039/100000002, National Institutes of Health;
                Award ID: P30AI094189
                Grant support was provided by the National Institutes of Health (NIH) including the National Institute on Drug Abuse and the National Institute of Allergy and Infectious Diseases (U01-DA-036297 [GDK, SHM], R01-DA-12568 [SHM], and T32-AI102623 [SHM]). This research was facilitated by the infrastructure and resources provided by the Johns Hopkins University Center for AIDS Research, an NIH funded program (P30AI094189), which is supported by the following NIH Co-Funding and Participating Institutes and Centers: NIAID, NCI, NICHD, NHLBI, NIDA, NIMH, NIA, FIC, NIGMS, NIDDK, and OAR. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
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                The data used in this study cannot be shared publicly because they contain sensitive participant information. As a part of the ethical approval of this study, the authors were required to sign a certificate of confidentiality per the National Institutes of Health. Thus, the data are available upon request to researchers who meet the criteria for access to confidential data. These data originate from the ALIVE study, which is considered a resource of the Johns Hopkins Department of Epidemiology (for more information, please see https://www.jhsph.edu/research/affiliated-programs/aids-linked-to-the-intravenous-experience/). Requests for data may be directed to the following authors of the present study: Dr. Shruti Mehta ( smehta@ 123456jhu.edu ; co-PI of the ALIVE study), Dr. Gregory D. Kirk ( gdk@ 123456jhu.edu ; co-PI of the ALIVE study), Jacquie Astemborski ( jastemb1@ 123456jhu.edu ), or to the ALIVE study ( 2213alive@ 123456gmail.com ). Data access queries will be evaluated according to the scientific premise of the research question, the availability of data to address the research question, and overlap with the existing investigation. An investigator from the present study will work with the person making the request to refine the question and interpret the data that is received. The authors confirm that the data will be available for the purposes of replication or verification of the results of the present study.

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