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Stimulant safe supply: a potential opportunity to respond to the overdose epidemic
Background
Occurring against the backdrop of an overdose crisis, stimulant use and stimulant-involved deaths in North America are increasing at an alarming rate. Many of these deaths are being attributed to fentanyl and related analogs, which have been increasingly found within street-level stimulant supplies. Within this, people experiencing socio-economic marginalization are at the greatest risk of overdose and other harms from adulterated stimulants. Current treatments for stimulant use disorder have limited effectiveness, and even less applicability to the lived realities of marginalized stimulant users. Emerging technologies, such as drug checking, are being implemented to support safer stimulant use, but the accessibility and utility of these technologies to stimulant users are framed by experiences of vulnerability that render them largely ineffective.
Stimulant safe supply
Solutions that provide a legal and safe supply of non-adulterated stimulants of known quality, and within a health care framework, are needed to directly address the risk of an increasingly adulterated stimulant supply. Similar innovative opioid-focused interventions are being piloted with medications that have a similar pharmacological effect as their illicit counterparts. While there are currently no approved pharmacotherapies for stimulant use, research has demonstrated a number of stimulant medications that are promising substitutes for cocaine and methamphetamine use. Much like with opioid-focused pharmacotherapies, having a consistent and safe supply of stimulants can lead to improved health outcomes and will drastically reduce overdose risk. However, for a stimulant safe supply intervention to be a success, it must provide the high and performance-enhancing effects that people seek from the illicit market, which requires doses and user agency that trials to date have not provided.
Conclusion
Efforts are needed to investigate the feasibility of pharmacological stimulant-based interventions that address safe supply needs. The promise of similar opioid-focused approaches in addressing both overdose-related risks and experiences related to vulnerability underscores the need to advance safe supply approaches targeted towards people who use stimulants. Given the current overdose crisis and rising stimulant use across North America, the implementation and evaluation of such novel stimulant-focused interventions should be a public health priority.
Journal Article
Insights Into the Role and Potential of Schwann Cells for Peripheral Nerve Repair From Studies of Development and Injury
Peripheral nerve injuries arising from trauma or disease can lead to sensory and motor deficits and neuropathic pain. Despite the purported ability of the peripheral nerve to self-repair, lifelong disability is common. New molecular and cellular insights have begun to reveal why the peripheral nerve has limited repair capacity. The peripheral nerve is primarily comprised of axons and Schwann cells, the supporting glial cells that produce myelin to facilitate the rapid conduction of electrical impulses. Schwann cells are required for successful nerve regeneration; they partially “de-differentiate” in response to injury, re-initiating the expression of developmental genes that support nerve repair. However, Schwann cell dysfunction, which occurs in chronic nerve injury, disease, and aging, limits their capacity to support endogenous repair, worsening patient outcomes. Cell replacement-based therapeutic approaches using exogenous Schwann cells could be curative, but not all Schwann cells have a “repair” phenotype, defined as the ability to promote axonal growth, maintain a proliferative phenotype, and remyelinate axons. Two cell replacement strategies are being championed for peripheral nerve repair: prospective isolation of “repair” Schwann cells for autologous cell transplants, which is hampered by supply challenges, and directed differentiation of pluripotent stem cells or lineage conversion of accessible somatic cells to induced Schwann cells, with the potential of “unlimited” supply. All approaches require a solid understanding of the molecular mechanisms guiding Schwann cell development and the repair phenotype, which we review herein. Together these studies provide essential context for current efforts to design glial cell-based therapies for peripheral nerve regeneration.
Journal Article
Women’s multiple uses of an overdose prevention technology to mitigate risks and harms within a supportive housing environment: a qualitative study
Background
North America is amidst an opioid overdose epidemic. In many settings, particularly Canada, the majority of overdose deaths occur indoors and impact structurally vulnerable people who use drugs alone, making targeted housing-based interventions a priority. Mobile applications have been developed that allow individuals to solicit help to prevent overdose death. We examine the experiences of women residents utilizing an overdose response button technology within a supportive housing environment.
Methods
In October 2019, we conducted semi-structured qualitative interviews with 14 residents of a women-only supportive housing building in an urban setting where the overdose response button technology was installed. Data was analyzed thematically and framed by theories of structural vulnerability.
Results
While participants described the utility and disadvantages of the technology for overdose response, most participants, unexpectedly described alternate adoptions of the technology. Participants used the technology for other emergency situations (e.g., gender-based violence), rather than its intended purpose of overdose response.
Conclusions
Our findings highlight the limitations of current technologies while also demonstrating the clear need for housing-based emergency response interventions that address not just overdose risk but also gender-based violence. These need to be implemented alongside larger strategies to address structural vulnerabilities and provide greater agency to marginalized women who use drugs.
Journal Article
Using alone at home: What’s missing in housing-based responses to the overdose crisis?
Background
Against the backdrop of North America’s overdose crisis, most overdose deaths are occurring in housing environments, largely due to individuals using drugs alone. Overdose deaths in cities remain concentrated in marginal housing environments (e.g., single-room occupancy housing, shelters), which are often the only forms of housing available to urban poor and drug-using communities. This commentary aims to highlight current housing-based overdose prevention interventions and to situate them within the broader environmental contexts of marginal housing. In doing so, we call attention to the need to better understand marginal housing as sites of overdose vulnerability and public health intervention to optimize responses to the overdose crisis.
Harm reduction and overdose prevention in housing
In response to high overdose rates in marginal housing environments several interventions (e.g., housing-based supervised consumption rooms, peer-witnessed injection) have recently been implemented in select jurisdictions. However, even with the growing recognition of marginal housing as a key intervention site, housing-based interventions have yet to be scaled up in a meaningful way. Further, there have been persistent challenges to tailoring these approaches to address dynamics within housing environments. Thus, while it is critical to expand coverage of housing-based interventions across marginal housing environments, these interventions must also attend to the contextual drivers of risks in these settings to best foster enabling environments for harm reduction and maximize impacts.
Conclusion
Emerging housing-focused interventions are designed to address key drivers of overdose risk (e.g., using alone, toxic drug supply). Yet, broader contextual factors (e.g., drug criminalization, housing quality, gender) are equally critical factors that shape how structurally vulnerable people who use drugs navigate and engage with harm reduction interventions. A more comprehensive understanding of these contextual factors within housing environments is needed to inform policy and programmatic interventions that are responsive to the needs of people who use drugs in these settings.
Journal Article
Direct Neuronal Reprogramming: Bridging the Gap Between Basic Science and Clinical Application
Direct neuronal reprogramming is an innovative new technology that involves the conversion of somatic cells to induced neurons (iNs) without passing through a pluripotent state. The capacity to make new neurons in the brain, which previously was not achievable, has created great excitement in the field as it has opened the door for the potential treatment of incurable neurodegenerative diseases and brain injuries such as stroke. These neurological disorders are associated with frank neuronal loss, and as new neurons are not made in most of the adult brain, treatment options are limited. Developmental biologists have paved the way for the field of direct neuronal reprogramming by identifying both intrinsic cues, primarily transcription factors (TFs) and miRNAs, and extrinsic cues, including growth factors and other signaling molecules, that induce neurogenesis and specify neuronal subtype identities in the embryonic brain. The striking observation that postmitotic, terminally differentiated somatic cells can be converted to iNs by mis-expression of TFs or miRNAs involved in neural lineage development, and/or by exposure to growth factors or small molecule cocktails that recapitulate the signaling environment of the developing brain, has opened the door to the rapid expansion of new neuronal reprogramming methodologies. Furthermore, the more recent applications of neuronal lineage conversion strategies that target resident glial cells
in situ
has expanded the clinical potential of direct neuronal reprogramming techniques. Herein, we present an overview of the history, accomplishments, and therapeutic potential of direct neuronal reprogramming as revealed over the last two decades.
Journal Article
Acceptability of a hypothetical preventative HIV vaccine among people who use drugs in Vancouver, Canada
Background
As research on HIV vaccines continues to advance, studies exploring the feasibility of this intervention are necessary to inform uptake and dissemination strategies with key populations, including people who use drugs (PWUD).
Methods
We conducted 25 in-depth qualitative interviews examining HIV vaccine acceptability among PWUD in Vancouver, Canada. Participants were recruited from an ongoing prospective cohort of HIV-negative PWUD. Data were coded using NVivo, and analyzed thematically.
Results
Acceptability was framed by practical considerations such as cost and side effects, and was influenced by broader trust of government bodies and health care professionals. While an HIV vaccine was perceived as an important prevention tool, willingness to be vaccinated was low. Results suggest that future vaccine implementation must consider how to minimize the burden an HIV vaccine may place on PWUD. Centering the role of health care providers in information dissemination and delivery may assist with uptake.
Conclusions
Our findings suggest improvements in care and improved patient-provider relationships would increase the acceptability of a potential HIV vaccine among this population.
Journal Article
Housing-based syringe services programs to improve access to safer injecting equipment for people who inject drugs in Vancouver, Canada: a spatially oriented qualitative study
Background
Housing environments shape injection drug-related risks and harms and thus represent a critical implementation setting for syringe services programs (SSPs). As critical harm reduction measures, SSPs provide safe injecting equipment to people who inject drugs (PWID). Vancouver, Canada, has well-established syringe distribution programs through which PWID have low-threshold access to unlimited syringes and related injecting equipment, including through non-profit operated supportive housing and single-room occupancy hotels. This study examines the role of housing-based SSPs in distributing injecting equipment to PWID in Vancouver.
Methods
Between January and March 2020, semi-structured, in-depth interviews were conducted in Vancouver with 26 PWID. Interviews were audio-recorded, transcribed, and coded. Salient themes were identified using inductive and deductive approaches.
Results
Many participants accessed SSPs in housing facilities and expressed preference for these programs over those offered at other locations and through other health and social services. Three major themes emerged to explain this preference. First, most participants injected in the buildings where they resided, and housing-based SSPs made injecting equipment available when and where it was most needed. Second, many participants preferred to avoid carrying syringes outside of the places where they inject due to fears that syringe possession may lead to criminal charges or confiscation of syringes and/or illicit drugs by police. Third, for some participants, anti-drug user stigma and concerns over unwillingly disclosing their drug use hindered access to SSPs outside of housing settings. Programs operated within housing facilities often offered greater client anonymity along with more supportive and less stigmatizing environments, particularly in the presence of peer staff.
Conclusion
The current study advances understanding of access to injecting equipment in a setting with city-wide syringe distribution programs. Our findings underscore the benefits of housing-based SSPs and encourage the expansion of such services to maximize access to harm reduction supports for PWID.
Journal Article
A qualitative investigation of HIV treatment dispensing models and impacts on adherence among people living with HIV who use drugs
Antiretroviral therapy (ART) dispensing is strongly associated with treatment adherence. Among illicit drug-using populations, whom experience greater structural barriers to adherence, directly administered antiretroviral therapy (DAAT) is often regarded as a stronger predictor of optimal adherence over self-administered medications. In Vancouver, Canada, people living with HIV (PLHIV) who use drugs and live in low-income housing are a critical population for treatment support. This group is typically able to access two key DAAT models, daily delivery and daily pickup, in addition to ART self-administration. This ethno-epidemiological qualitative study explores how key dispensing models impact ART adherence among PLHIV who use drugs living in low-income housing, and how this is framed by structural vulnerability. Semi-structured interviews lasting 30–45 minutes were conducted between February and May 2018 with 31 PLHIV who use drugs recruited from an ongoing prospective cohort of PLHIV who use drugs. Interviews were audio-recorded, transcribed verbatim, and analyzed using QSR International’s NVivo 12 software. Interviews focused on housing, drug use, and HIV management. Models that constrained agency were found to have negative impacts on adherence and quality of life. Treatment interruptions were framed by structural vulnerabilities (e.g., housing vulnerability) that impacted ability to maintain adherence under certain dispensing models, and led participants to consider other models. Participants using DAAT models which accounted for their structural vulnerabilities (e.g., mobility issues, housing instability), credited these models for their treatment adherence, but also acknowledged factors that constrained agency, and the negative impacts this could have on both adherence, and quality of life. Being able to integrate ART into an established routine is key to supporting ART adherence. ART models that account for the structural vulnerability of PLHIV who use drugs and live in low-income housing are necessary and housing-based supports could be critical, but the impacts of such models on agency must be considered to ensure optimal adherence.
Journal Article
Beyond Genetics: The Role of Metabolism in Photoreceptor Survival, Development and Repair
Vision commences in the retina with rod and cone photoreceptors that detect and convert light to electrical signals. The irreversible loss of photoreceptors due to neurodegenerative disease leads to visual impairment and blindness. Interventions now in development include transplanting photoreceptors, committed photoreceptor precursors, or retinal pigment epithelial (RPE) cells, with the latter protecting photoreceptors from dying. However, introducing exogenous human cells in a clinical setting faces both regulatory and supply chain hurdles. Recent work has shown that abnormalities in central cell metabolism pathways are an underlying feature of most neurodegenerative disorders, including those in the retina. Reversal of key metabolic alterations to drive retinal repair thus represents a novel strategy to treat vision loss based on cell regeneration. Here, we review the connection between photoreceptor degeneration and alterations in cell metabolism, along with new insights into how metabolic reprogramming drives both retinal development and repair following damage. The potential impact of metabolic reprogramming on retinal regeneration is also discussed, specifically in the context of how metabolic switches drive both retinal development and the activation of retinal glial cells known as Müller glia. Müller glia display latent regenerative properties in teleost fish, however, their capacity to regenerate new photoreceptors has been lost in mammals. Thus, re-activating the regenerative properties of Müller glia in mammals represents an exciting new area that integrates research into developmental cues, central metabolism, disease mechanisms, and glial cell biology. In addition, we discuss this work in relation to the latest insights gleaned from other tissues (brain, muscle) and regenerative species (zebrafish).
Journal Article