The effect of prescription opioid injection on the risk of non-fatal overdose among people who inject drugs
Introduction
An epidemic of opioid-related overdose deaths in North America has followed from substantial increases in the use of prescription opioid analgesics (POs; Centers for Disease Control and Prevention, 2012, Cerda et al., 2013, Manchikanti and Singh, 2008). The use of diverted POs among high-risk substance-using populations, including people who inject drugs (PWID), has also increased (Bruneau et al., 2012, Fischer et al., 2008). While alarmingly high rates of PO injection have been documented in rural areas where access to a range of illicit drugs may be limited (Havens et al., 2007), accounts from urban drug centers have also demonstrated that despite high accessibility of heroin, the availability of diverted POs has also increased (Nosyk et al., 2012). While the association between PO use and accidental overdose in the general public has been well-established (Bohnert et al., 2011, Dart et al., 2015, Fischer et al., 2014), the impact of illicit PO use on overdose among long-term drug users, such as PWID, is not known.
Overdose remains a leading cause of morbidity and mortality among PWID (Degenhardt and Hall, 2012, Miller et al., 2007, Warner-Smith et al., 2002), and is prevalent with roughly 30–45% of PWID having experienced at least one non-fatal overdose in their lifetime (Havens et al., 2011, Kerr et al., 2007, Ochoa et al., 2005, Pollini et al., 2006, Sherman et al., 2007), and as many as 20% reporting a non-fatal overdose in the previous year (Ochoa et al., 2005). The health consequences of non-fatal overdose can be severe and include a range of injuries such as acute hypoxia including neurological (e.g., stroke) and solid organ (e.g., renal failure) concerns (Warner-Smith et al., 2002, Warner-Smith et al., 2001). Furthermore, those who have survived an overdose are at a heightened risk for future overdose (Darke et al., 2005, Kinner et al., 2012), including fatal overdose (Stoove et al., 2009). Non-fatal overdose also poses a major burden on the health care system as a leading reason for emergency department presentation (Palepu et al., 2001), which can result in long term institutionalization among those with severe neurological injuries.
Past research has identified a significant positive association between PO use (i.e., oral, intranasal, or intravenous administration) and non-fatal overdose (Lake et al., 2015), and has also found that among PO-using young adults, non-fatal overdose is more common among those who inject POs (Silva et al., 2013b). However, few studies have explored a potential independent association between PO injection and non-fatal overdose among PWID. While many PWID have long-term experience with heroin injection, the harms associated with PO injection may be perceived as comparatively less threatening: despite similarities in pharmacological effect (Trescot et al., 2008), key differences in the composition and preparation of these two types of drugs may produce different overdose risks. For example, whereas POs are manufactured for licit use and maintain consistent doses and purities, these characteristics may be unpredictable in heroin due to it being unregulated (Werb et al., 2013).
As PO injection becomes more prevalent among high-risk drug using populations, understanding the effect of PO injection is critical to overdose prevention efforts. The present study therefore aims to investigate the effect of PO injection on non-fatal overdose among PWID.
Section snippets
Study sample
The Vancouver Injection Drug Users Study (VIDUS) and the AIDS Care Cohort to Evaluate Exposure to Survival Services (ACCESS) are ongoing open prospective cohorts of adults who use illicit drugs recruited through self-referral and street outreach in Vancouver, Canada. The cohorts have been described in detail previously (Strathdee et al., 1998). Briefly, VIDUS enrolls HIV-negative people who report injecting an illicit drug at least once in the previous month; ACCESS enrolls HIV-positive people
Results
Between December, 2005 and May, 2014, 1660 actively injecting study participants, including 559 (33.7%) women, completed a total 10,919 study visits. Of these 10,919 observations, 233 (2.1%) were removed from the analysis due to invalid or missing values, yielding a total of 10,686 analytic observations. The median number of follow up visits was 5 (interquartile range [IQR]: 2–10). The baseline median age of the sample was 42.1 years (IQR: 35.5–48.0). The proportion of PWID reporting injection
Discussion
Over the study period, approximately one-quarter of participants reported recent injection of POs, which is comparatively lower than the roughly one-half (Leclerc et al., 2011) and three-quarters (Bruneau et al., 2012) of PWID who report injecting POs in other Canadian settings. Our comparatively lower PO injection rates may be due, in part, to the presence of a controlled prescription program in British Columbia designed to educate physicians about proper opioid prescribing practices (Richard
Role of funding source
This study was supported by theUS National Institutes of Health (R01DA021525 and U01DA038886), and was undertaken, in part, from funding through a Tier 1 Canada Research Chair in Inner City Medicine, which supports Dr. Evan Wood. Dr. M.-J. Milloy is supported in part by the United States National Institutes of Health (R01-DA021525). Dr. Kanna Hayashi is supported by a fellowship from the Canadian Institutes of Health Research. Beyond providing financial support, the funders did not contribute
Contributors
This study was designed by SL and TK, and the primary manuscript draft was written by SL. All authors contributed to manuscript revision and approved the final version for submission. HD carried out all statistical procedures.
Conflict of interest
Dr. Julio Montaner has received educational grants from, served as an ad hoc advisor to, or spoken at various events sponsored by: Abbott Laboratories, Agouron Pharmaceuticals Inc., Boehringer Ingelheim Pharmaceuticals Inc., Borean Pharma AS, Bristol-Myers Squibb, DuPont Pharma, Gilead Sciences, GlaxoSmithKline, Hoffman-La Roche, Immune Response Corporation, Incyte, Janssen-Ortho Inc., Kucera Pharmaceutical Company, Merck Frosst Laboratories, Pfizer Canada Inc., Sanofi Pasteur, Shire Biochem
Acknowledgments
We extend our gratitude to the participants in both the VIDUS and ACCESS studies for their contribution to this research, as well as current and past study researchers and staff. We would also like to thank the staff of the British Columbia Centre for Excellence in HIV/AIDS – specifically Tricia Collingham, Carmen Rock, Kristie Starr, Sabina Dobrer, Deborah Graham, Peter Vann, Jennifer Matthews, Steve Kain, and Calvin Lai for their research and administrative assistance.
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