Accessibility gaps of physical supervised consumption sites in Canada motivating the use of overdose response technology/phone based virtual overdose response services: a retrospective cohort study.

Background: Overdose response technology or virtual overdose response services are an evolving complementary harm reduction intervention which may overcome certain accessibility barriers of physical supervised consumption sites (SCS) and overdose prevention sites (OPS). We sought to characterize SCS/OPS accessibility barriers among clients accessing a nationwide overdose response phone-based hotline in Canada. Methods: We performed a retrospective cohort analysis using anonymized call logs of the National Overdose Response Service (NORS) between December 2020 to July 2023. De-identified caller locations were cross-referenced with the locations, policies and operational hours of existing physical SCS/OPS. The primary outcome was accessibility of physical SCS/OPS defined hierarchically according to alignment with caller postal code, substance use routes reported, and calling times. Findings: Our cohort comprised 4501 calls from 331 unique clients. Despite always having nearby SCS/OPS open and supporting substance use routes of choice, 100 clients (30.2%) preferentially utilized NORS. Among 191 clients (57.7%) who never had access to physical SCS/OPS at time of calling, 92 (27.8%) lacked a nearby site, 58 (17.5%) called outside of operational hours, and 41 (12.4%) would not be permitted to smoke on premises. Secondary analyses identified correlations between accessibility and the urbanicity and geographical region of callers within Canada. Interpretation: Overdose response technology or virtual overdose response services are a novel complementary harm reduction strategy both for clients with access barriers to physical SCS/OPS and those who prefer virtual services. System-level correlates of client location urbanicity and inter-provincial variation indicate actionable targets for expanding harm reduction services both physical and virtual to better engage with people who use drugs. Funding: Health Canada Substance Use and Addictions Program, Canadian Institutes of Health Research, and Grenfell Ministries.

Opioid agonist therapy switching among individuals with prescription-type opioid use disorder: Secondary analysis of a pragmatic randomized trial.

BACKGROUND: Engagement and retention in opioid agonist therapy (OAT) remains a challenge. This study evaluated the impact of initial randomized OAT allocation on subsequent switching among people with prescription-type opioid use disorder (POUD). METHODS: Secondary analysis of a 24-week Canadian multicenter, pragmatic, randomized trial conducted between 2017 and 2020 comparing flexible take-home buprenorphine/naloxone versus supervised methadone models of care for POUD. We used Cox Proportional Hazards modeling to assess for impact of treatment assignment on time to OAT switching, adjusting for important confounders. For clinical correlates, we analyzed data from baseline questionnaires on demographic, substance use, and health factors as well as urine drug screen. RESULTS: Of 272 randomized participants, 210 initiated OAT within 14 days per trial protocol, of whom 103 participants were randomized to buprenorphine/naloxone and 107 to methadone. Within 24-week follow-up, 41 (20.5%) of all participants switched OAT with 25 (24.3%, median 27 days, 88.4 per 100 person-years) and 16 participants (15.0%, median 53.5 days, 46.1 per 100 person-years) switching from buprenorphine/naloxone and methadone arms, respectively. In adjusted analysis, allocation to buprenorphine/naloxone was associated with significantly higher risk of switching (aHR = 2.31, 95% CI 1.22 - 4.38). CONCLUSIONS: OAT switching was common in this sample of individuals with POUD, with individuals randomly allocated to buprenorphine/naloxone being more than twice as likely to switch versus methadone. This may reflect a stepped care approach in OUD management. More research is needed to evaluate overall retention and outcomes with the different observed risks of switching between methadone and buprenorphine/naloxone.

Alcohol use disorder with comorbid anxiety disorder: a case report and focused literature review.

BACKGROUND: Alcohol use disorder (AUD) and anxiety disorders (AnxD) are prevalent health concerns in clinical practice which frequently co-occur (AUD-AnxD) and compound one another. Concurrent AUD-AnxD poses a challenge for clinical management as approaches to treatment of one disorder may be ineffective or potentially counterproductive for the other disorder. CASE PRESENTATION: We present the case of a middle-aged man with anxiety disorder, AUD, chronic pain, and gamma-hydroxybutyrate use in context of tapering prescribed benzodiazepines who experienced severe alcohol withdrawal episodes during a complicated course of repeated inpatient withdrawal management. After medical stabilization, the patient found significant improvement in symptoms and no return to alcohol use with a regimen of naltrexone targeting his AUD, gabapentin targeting both his AUD and AnxD, and engagement with integrated psychotherapy, Alcoholics Anonymous, and addictions medicine follow-up. CONCLUSION: Proper recognition and interventions for AUD and AnxD, ideally with overlapping efficacy, can benefit individuals with comorbid AUD-AnxD. Gabapentin, tobacco cessation, and integrated psychotherapy have preliminary evidence of synergistic effects in AUD-AnxD. Meta-analysis evidence does not support serotoninergic medications (e.g. selective serotonin reuptake inhibitors) which are commonly prescribed in AnxD and mood disorders as their use has not been associated with improved outcomes for AUD-AnxD. Additionally, several double-blind placebo-controlled randomized trials have suggested that serotonergic medications may worsen alcohol-related outcomes in some individuals with AUD. Areas for future investigation are highlighted.

Safety considerations in the evolving legal landscape of psychedelic-assisted psychotherapy.

International drug policy is rapidly evolving in tandem with promising evidence for psychedelic-assisted psychotherapy (PAP) in treating a range of mental health conditions. Canada is among the countries increasingly expanding access to psychedelic substances for therapeutic purposes. The 8-year ban on medical exemptions through the Canadian Special Access Programme was recently reversed in January 2022 and the first exemptions for legal possession and personal use of psilocybin mushrooms were granted in 2020, nearly 50 years since their criminalization. In view of the evolving evidence base and regulatory landscape for PAP illustrated by recent shifts in Canadian and international drug policy, this piece seeks to clarify the special range of factors which ought to be considered to safely expand access to psychedelics. Streamlining access to safe and evidence-based compassionate use of PAP will provide a timely treatment option to those currently in need while encouraging further research and outcome surveillance to refine best practices.

Optical Imaging-Based Guidance of Viral Microinjections and Insertion of a Laminar Electrophysiology Probe Into a Predetermined Barrel in Mouse Area S1BF.

Wide-field Optical Imaging of Intrinsic Signals (OI-IS; Grinvald et al., 1986) is a method for imaging functional brain hemodynamic responses, mainly used to image activity from the surface of the cerebral cortex. It localizes small functional modules - such as cortical columns - with great spatial resolution and spatial specificity relative to the site of increases in neuronal activity. OI-IS is capable of imaging responses either through an intact or thinned skull or following a craniotomy. Therefore, it is minimally invasive, which makes it ideal for survival experiments. Here we describe OI-IS-based methods for guiding microinjections of optogenetics viral vectors in proximity to small functional modules (S1 barrels) of the cerebral cortex and for guiding the insertion of electrodes for electrophysiological recording into such modules. We validate our proposed methods by tissue processing of the cerebral barrel field area, revealing the track of the electrode in a predetermined barrel. In addition, we demonstrate the use of optical imaging to visualize the spatial extent of the optogenetics photostimulation, making it possible to estimate one of the two variables that conjointly determine which region of the brain is stimulated. Lastly, we demonstrate the use of OI-IS at high-magnification for imaging the upper recording contacts of a laminar probe, making it possible to estimate the insertion depth of all contacts relative to the surface of the cortex. These methods support the precise positioning of microinjections and recording electrodes, thus overcoming the variability in the spatial position of fine-scale functional modules.

Use and disuse of malaria bed nets in an internally displaced persons camp in the Democratic Republic of the Congo: A mixed-methods study.

INTRODUCTION: Malaria is a major cause of morbidity and mortality among displaced populations in tropical zones. Bed nets are widely used to prevent malaria; however, few data are available on bed net distribution within displaced populations. METHODS: Mixed methods study in a single internally displaced persons (IDP) camp and neighboring community in Eastern Democratic Republic of the Congo (DRC). Qualitative data (focus group discussions, FGDs) and quantitative data (door-to-door survey and individual testing using malaria rapid diagnostic test, RDT) were collected. RESULTS: Ten FGDs were conducted with 55 individuals. Although malaria was widely recognized as a significant threat and bed nets were freely distributed in the camp, many households did not own or use them. IDPs converged on the following reasons for low bed net ownership and use: inconvenience of net installation and sale of nets to meet immediate needs such as food. One hundred households, comprised of 411 individuals, were surveyed in Birambizo. The burden of malaria was high (45/78 (58%) of children <5 were positive for malaria by RDT) and bed net utilization was low (29/100 (29%) households owned a bed net, and 85/411 (20%) individuals slept under a bed net the previous night). Children <5 were more likely to use a bed net than older children or adults (OR 3.4 (95%CI 2.0-5.8), p<0.0001). Compared to 29 bed nets currently in use by study participants, 146 bed nets had been sold (82%) or exchanged (18%) either in the camp (27%) or in the neighbouring village market (73%). CONCLUSIONS: Qualitative descriptions and quantitative analysis revealed pragmatic barriers to bed net usage and widespread sale of freely distributed bed nets within IDP camps, despite a high burden of malaria. Additional strategies, beyond bed net distribution, are warranted to combat malaria in vulnerable and hard-to-reach population.

Laminar Distribution of Phase-Amplitude Coupling of Spontaneous Current Sources and Sinks.

Although resting-state functional connectivity is a commonly used neuroimaging paradigm, the underlying mechanisms remain unknown. Thalamo-cortical and cortico-cortical circuits generate oscillations at different frequencies during spontaneous activity. However, it remains unclear how the various rhythms interact and whether their interactions are lamina-specific. Here we investigated intra- and inter-laminar spontaneous phase-amplitude coupling (PAC). We recorded local-field potentials using laminar probes inserted in the forelimb representation of rat area S1. We then computed time-series of frequency-band- and lamina-specific current source density (CSD), and PACs of CSD for all possible pairs of the classical frequency bands in the range of 1-150 Hz. We observed both intra- and inter-laminar spontaneous PAC. Of 18 possible combinations, 12 showed PAC, with the highest measures of interaction obtained for the pairs of the theta/gamma and delta/gamma bands. Intra- and inter-laminar PACs involving layers 2/3-5a were higher than those involving layer 6. Current sinks (sources) in the delta band were associated with increased (decreased) amplitudes of high-frequency signals in the beta to fast gamma bands throughout layers 2/3-6. Spontaneous sinks (sources) of the theta and alpha bands in layers 2/3-4 were on average linked to dipoles completed by sources (sinks) in layer 6, associated with high (low) amplitudes of the beta to fast-gamma bands in the entire cortical column. Our findings show that during spontaneous activity, delta, theta, and alpha oscillations are associated with periodic excitability, which for the theta and alpha bands is lamina-dependent. They further emphasize the differences between the function of layer 6 and that of the superficial layers, and the role of layer 6 in controlling activity in those layers. Our study links theories on the involvement of PAC in resting-state functional connectivity with previous work that revealed lamina-specific anatomical thalamo-cortico-cortical connections.