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- Page navigation anchor for RE: Safer Opioid Supply Programs Have Unintended ConsequencesRE: Safer Opioid Supply Programs Have Unintended Consequences
We appreciate the opportunity to respond to Dr. Koivu’s comments. As described in our manuscript, we agree that further research examining the extent and impacts of sharing hydromorphone within communities is needed. However, we also believe that it is unlikely that LIHC clients were broadly sharing their medication given the observed improvements in their health status and health care use - including reductions in hospitalizations for infection - during a period in which we did not see these same trends in the matched group of London residents with opioid use disorder without access to a safer opioid supply (SOS)(1). Furthermore, an important distinction from the literature cited by Dr. Koivu is that the London SOS program prescribes immediate-release (IR) hydromorphone as a method to avoid the potentially increased risk of infectious complications when injecting controlled-release formulations of this drug. Research published by Dr. Koivu and others has demonstrated that the same risks of infections are not observed with the IR formulation of hydromorphone (2).
Finally, we believe that it is important to note that the increased prevalence of fentanyl in the unregulated drug supply and corresponding increases in opioid toxicity deaths that Dr. Koivu describes in London since 2016 when the SOS program began are broadly representative of trends that have been observed across Canada over this same period (3, 4). Therefore, while trends towards higher fentanyl use an...
Show MoreCompeting Interests: Tara Gomes reports receiving grants paid to support the research program from the Ontario Ministry of Health, a grant paid to support the conduct of the study from the Canadian Institutes of Health Research (CIHR) and Canada Research Chair funding for salary support. Andrea Sereda is the medical lead in the Safer Opioid Supply program based out of the London InterCommunity Health Centre (LIHC). Dr. Sereda has also received support for attending meetings or travel from the LIHC (as an employee). Gillian Kolla is supported by a Banting postdoctoral fellowship from the CIHR and a postdoctoral fellowship from the Canadian Network on Hepatitis C. Separate from this study, Dr. Kolla received funding from LIHC’s Substance Use and Addictions Program grant to conduct an independent preliminary evaluation of the Safer Opioid Supply program. No other competing interests were declared.References
- Gomes T, Kolla G, McCormack D et al. Clinical outcomes and health care costs among people entering a safer opioid supply program in Ontario. CMAJ 2022; 194(36): E1233-E124
- Silverman M, Slater J, Jandoc R et al. Hydromorphone and the risk of infective endocarditis among people who inject drugs: a population-based, retrospective cohort study. Lancet Infect Dis 2022; 20(4):487-497
- Gomes T, Juurlink DN. Understanding the Implications of a Shifting Opioid Landscape in Ontario. Healthcare Quarterly 2019; 22(3): 6-11
- Government of Canada. Opioid- and Stimulant-related Harms in Canada. September 2022. https://health-infobase.canada.ca/substance-related-harms/opioids-stimulants/
- Page navigation anchor for RE: Response to Drs. Bromley and KahanRE: Response to Drs. Bromley and Kahan
We appreciate the opportunity to respond to letters from Dr. Bromley and Dr. Kahan regarding our study. We agree that infection is a potential concern with the injection of hydromorphone tablets, and were reassured to observe in our study that rates of infectious complications among Safer Opioid Supply (SOS) program clients declined in the year following enrolment (1). This finding aligns with past research demonstrating that the association with endocarditis is stronger for long-acting hydromorphone formulations relative to the immediate-release hydromorphone tablets (2,3) used in SOS programs, and may also reflect the education and access to sterile injection equipment provided to SOS clients.
We could not study the extent to which sharing of SOS medications was occurring, and agree that further research in this regard is required. We also agree that comparisons of SOS with opioid agonist treatment (OAT) are warranted. The study cited by Dr. Kahan cannot make plausible causal claims of the relative safety of oral morphine compared to OAT because of its cross-sectional design, where exposure and outcomes appear to have been ascertained simultaneously (4). Moreover, there was no difference in the risk of overdose between individuals receiving regularly dosed morphine or methadone, with the authors concluding that "the main objective is to promote a regular 'conventional OMT [opioid maintenance treatment]-like' prescription” when using formulations of...
Show MoreCompeting Interests: None declared.References
- 1 - Gomes, T., Kolla, G., McCormack, D., Sereda, A., Kitchen, S., & Antoniou, T. (2022). Clinical outcomes and health care costs among people entering a safer opioid supply program in Ontario. CMAJ, 194(36), E1233-E1242.
- 2 - Silverman M, Slater J, Jandoc R, Koivu S, Garg AX, Weir MA. Hydromorphone and the risk of infective endocarditis among people who inject drugs: a population-based, retrospective cohort study. Lancet Infect Dis. 2020;20(4):487-497.
- 3 - Kasper KJ, Manoharan I, Hallam B, et al. A controlled-release oral opioid supports S. aureus survival in injection drug preparation equipment and may increase bacteremia and endocarditis risk. PLoS One. 2019;14(8):e0219777.
- 4 - Bertin C, Bezin J, Chenaf C, et al. Oral morphine as an alternative substitution treatment for opioid use disorder, a rare but non-risk-free use. Frontiers in Psychiatry 13, 2022: Article 893590.
- Page navigation anchor for RE: Safer Opioid Supply Programs Have Unintended ConsequencesRE: Safer Opioid Supply Programs Have Unintended Consequences
“Safe Supply” has unintended consequences and negative side effects.
I have worked as an inpatient Addiction Physician since 2012. I lived near London Intercommunity Health Centre from 2015-2021, to promote harm reduction.
After OxyContin, London had a high use of hydomorphone CR. An infectious Disease Specialist and I observed a correlation between injection of hydomorphone CR and both Tricuspid Valve infective Endocarditis and HIV. (1) Research teams proved these causations. (2) We have multiple published work. (1,2,4) We launched a successful community-based education campaign. TV IE and HIV decreased. (3)
I was initially optimistic about “Safe Supply” but soon began identifying concerns. Since Safe Supply, severe infections from injection drug use have increased. I witnessed an increase in spinal OM and epidural abscesses and resulting horrific suffering.
I have known patients in the program who died of overdose.
London has had an increase in Fentanyl availability, use and overdose deaths since the program began. I have had patients tell me they sell their hydromorphone Immediate Release to buy Fentanyl.
I observed a significant reduction in the percentage of my patients who would initiate or continue Opioid Agonist Therapy. Patients wanted the income from diverting “Safe Supply”.
Housing is destabilized. I have had housed patients leave their homes to live in tents near the pharmacy where much diversion takes place....
Show MoreCompeting Interests: None declared.References
- Weir M , Slater J, Jandoc R, et al. The risk of infective endocarditis among people who inject drugs: a retrospective, population based time series analysis. CMAJ 2019;28:E93-9.
- Silverman M, Slater J, Jandoc R, et al. Hydromorphone and the risk of infective endocarditis among people who inject drugs: a population-based, retrospective cohort study. Lancet Infect Dis 2020;20:487-497.
- Ball LJ, Venner C, Tirona RG, et al. Heating Injection Drug Preparation Equipment Used for Opioid Injection May Reduce HIV Transmission Associated With Sharing Equipment. J Acquir Immune Defic Syndr 2019;81:e127-34.
- Johnstone R, Khalil N, Shojaei E, et al. Different drugs, different sides: injection use of opioids alone, and not stimulants alone, predisposes to right-sided endocarditis. Open Heart 2022;9:e001930.
- Page navigation anchor for RE: Infections and diversion in safer supply programsRE: Infections and diversion in safer supply programs
Participants in safer supply programs access a prescription medication product delivered in a medical setting. Oral hydromorphone tablets used in the programs contain excipients which are not recommended for injection use and are not sterile. In this medicalized access model, it should be feasible to achieve a rate of serious infections close to zero by using sterile injectable medications. Many safer supply programs are funded by grants from Health Canada’s Substance Use and Addiction Program (SUAP). While injectable meds in sufficient concentration are not currently covered on provincial drug Formularies, safer supply programs could provide access to sterile injectable meds by adding a budget line in SUAP grants for medication costs. It’s not clear if participants in safer supply programs are advised that sterile injectable medications exist, or are offered a choice to use an injectable medication to reduce their risk of developing painful, disabling, costly, and sometimes fatal infections such as osteomyelitis, epidural abscess, or endocarditis.
Safer supply prescription tablet programs have an impact on the surrounding community. Because doses are unsupervised, they can be shared with others who are not part of a program. Safer supply practitioners have written a document on reframing diversion, which presents diverted hydromorphone tablets as a form of mutual aid within a community at high risk of fentanyl poisoning death. This assumes tablets stay sequestered...
Show MoreCompeting Interests: honorarium from Master Clinician Alliance for development of education materials for Opioid Use DisorderReferences
- https://www.nss-aps.ca/reframing-diversion-prescribers
- https://www.canada.ca/content/dam/hc-sc/documents/corporate/about-health-canada/public-engagement/external-advisory-bodies/reports/report-2-2021/report-2-HC-expert-task-force-on-substance-use-final-en.pdf
- Page navigation anchor for RE: : Safer opioid supply should be compared to Opioid Agonist TreatmentRE: : Safer opioid supply should be compared to Opioid Agonist Treatment
The Safe Supply (SOS) cohort had better outcomes than those in the comparison group. However, in the comparison group, only 38% had received opioid agonist treatment (OAT) with methadone or buprenorphine within the past 30 days at baseline. The authors should clarify how many were on OAT at the start of the study, and what their outcomes were compared to those not on OAT. It would not be surprising if the Safe Supply (SOS) cohort had better outcomes than those who were on no treatment. Any oral opioid agonist will reduce opioid use by mitigating withdrawal symptoms and cravings. What is needed is a study comparing patients on Safe Supply with patients who are currently on Opioid Agonist Treatment (OAT). OAT prescribers have reported that some patients have entered Safe Supply programs even though they were doing well on OAT, or had done well on it in the past. If patients are choosing SOS over OAT, it is important that the two treatments be compared with respect to safety and effectiveness.
Such a comparison will likely demonstrate that OAT is more effective at preventing bacterial infections. There is strong evidence that OAT markedly reduces hospitalizations for injection-related infections (1-3). This is because methadone and buprenorphine are usually dispensed under supervision until the patient is stable. In contrast, SOS patients are prescribed take-home hydromorphone tablets, which they can inject without supervision. The only direct comparison we...
Show MoreCompeting Interests: None declared.References
- 1. Brothers T, Lewer D, Jones N, et al. Opioid agonist treatment and risk of death or rehospitalization following injection drug use-associated bacterial and fungal infections: A cohort study in New South Wales, Australia. PLOS Medicine July 19, 2022
- 2. Karki P, Shrestha R, Huedo-Medina TB, et al. The Impact of Methadone Maintenance Treatment on HIV Risk Behaviors among High-Risk Injection Drug Users: A Systematic Review. Evid Based Med Public Health. 2016;2.
- 3. Morin KA, Prevost CR, Eibl JK, et al. A retrospective cohort study evaluating correlates of deep tissue infections among patients enrolled in opioid agonist treatment using administrative data in Ontario, Canada. PLoS One. 2020 Apr 24;15(4):e0232191.
- 4. Bertin C, Bezin J, Chenaf C, et al. Oral morphine as an alternative substitution treatment for opioid use disorder, a rare but non-risk-free use. Frontiers in Psychiatry 13, 2022: article 893590
- 5. Bromley L, Kahan M, Regenstreif L, et al. Methadone treatment for people who use fentanyl: Recommendations. Toronto, ON: META:PHI; 2021. www.metaphi.ca.