Abstract
Background
Canada is in the midst of an opioid overdose crisis and Alberta has one of the highest opioid use rates across the country. Populations made vulnerable through structural ...inequities who also use opioids, such as those who are unstably housed, are at an increased risk of experiencing harms associated with opioid use. The main purpose of this study was to explore if there was an association between unstable housing and hospital use for people who use opioids.
Methods
Analysis utilized self-reported data from the Alberta Health and Drug Use Survey which surveyed 813 Albertans in three cities. Hospital use was modeled using a logistic regression with our primary variable of interest being housing unstable status. Chi square tests were conducted between hospital use and variables associated with demographics, characteristics of drug use, health characteristics, and experiences of receiving services to establish model inclusion.
Results
Results revealed a significant association between housing instability and hospital use with unstably housed individuals twice as likely torequire hospital care.
Conclusions
Results highlight the importance of concurrently addressing housing instability alongside the provision of harm reduction services such as safe supply and supervised consumption sites. These findings have significant implications for policy and policymakers during the opioid overdose epidemic, and provide a foundation for future areas of research.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Plant-derived cannabinoids (phytocannabinoids) are compounds with emerging therapeutic potential. Early studies suggested that cannabidiol (CBD) has anticonvulsant properties in animal models and ...reduced seizure frequency in limited human trials. Here, we examine the antiepileptiform and antiseizure potential of CBD using in vitro electrophysiology and an in vivo animal seizure model, respectively. CBD (0.01-100 muM) effects were assessed in vitro using the Mg(2+)-free and 4-aminopyridine (4-AP) models of epileptiform activity in hippocampal brain slices via multielectrode array recordings. In the Mg(2+)-free model, CBD decreased epileptiform local field potential (LFP) burst amplitude in CA1 and dentate gyrus (DG) regions and burst duration (in all regions) and increased burst frequency (in all regions). In the 4-AP model, CBD decreased LFP burst amplitude (in CA1 only at 100 muM CBD), burst duration (in CA3 and DG), and burst frequency (in all regions). CBD (1, 10, and 100 mg/kg) effects were also examined in vivo using the pentylenetetrazole model of generalized seizures. CBD (100 mg/kg) exerted clear anticonvulsant effects with significant decreases in incidence of severe seizures and mortality compared with vehicle-treated animals. Finally, CBD acted with only low affinity at cannabinoid CB(1) receptors and displayed no agonist activity in (35)Sguanosine 5'-O-(3-thio)triphosphate assays in cortical membranes. These findings suggest that CBD acts, potentially in a CB(1) receptor-independent manner, to inhibit epileptiform activity in vitro and seizure severity in vivo. Thus, we demonstrate the potential of CBD as a novel antiepileptic drug in the unmet clinical need associated with generalized seizures.
The Cannabis sativa herb contains over 100 phytocannabinoid (pCB) compounds and has been used for thousands of years for both recreational and medicinal purposes. In the past two decades, ...characterisation of the body's endogenous cannabinoid (CB) (endocannabinoid, eCB) system (ECS) has highlighted activation of central CB(1) receptors by the major pCB, Δ(9)-tetrahydrocannabinol (Δ(9)-THC) as the primary mediator of the psychoactive, hyperphagic and some of the potentially therapeutic properties of ingested cannabis. Whilst Δ(9)-THC is the most prevalent and widely studied pCB, it is also the predominant psychotropic component of cannabis, a property that likely limits its widespread therapeutic use as an isolated agent. In this regard, research focus has recently widened to include other pCBs including cannabidiol (CBD), cannabigerol (CBG), Δ(9)tetrahydrocannabivarin (Δ(9)-THCV) and cannabidivarin (CBDV), some of which show potential as therapeutic agents in preclinical models of CNS disease. Moreover, it is becoming evident that these non-Δ(9)-THC pCBs act at a wide range of pharmacological targets, not solely limited to CB receptors. Disorders that could be targeted include epilepsy, neurodegenerative diseases, affective disorders and the central modulation of feeding behaviour. Here, we review pCB effects in preclinical models of CNS disease and, where available, clinical trial data that support therapeutic effects. Such developments may soon yield the first non-Δ(9)-THC pCB-based medicines.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Adequate clinical skills training is a challenge for present day medical education. Simulation Based Education (SBE) is playing an increasingly important role in healthcare education worldwide to ...teach invasive procedures. The impact of this teaching on students along with retention of what is taught is not fully understood. The purpose of this study was to evaluate the retention levels of practical skills taught and assessed by SBE and to explore the degree of re-training required to restore decayed performance. In exploring this aim, the study further investigates how skilled performance decays over time and which dimensions of clinical skills were more likely to decay.
Study participants were 51 final year medical students. They were provided with online pre-course videos and procedural guides asynchronously with repeatedly access. 7 of the skills taught over 2 years using task trainers were selected. Following demonstration from faculty, students practiced in small groups with faculty facilitated supervision and peer support prior to formal testing. Score sheets with itemised procedure checklists detailing the minimum passing standard (MPS) for each skill were designed. To test retention of skills, 18 months later, there was an unannounced test to demonstrate proficiency in the skills. Students were asked to complete a questionnaire indicating how many times and where they had practiced or performed the skills.
55% of the students were deficient in 3 or more skills and 4% were not competent in 5 or more skills. A significant number of students had never practiced some skills following the initial teaching session. A relationship was noted with the number of times students self-declared that they had practiced and their performance. Decay is evident in both psychomotor and cognitive domains of the skills.
A curriculum with deliberate practice significantly increases the competence of students in defined clinical skills. Deliberate practice of clinical skills, under supervision of an engaged instructor, is a key component of the mastery model. Experiences and assessments in the clinical setting need to be augmented with focus on direct observation and focused feedback to reinforce the skills acquired in the simulated setting.
Knowledge production in entrepreneurship requires inclusivity as well as diversity and pluralism in research perspectives and approaches. In this article, the authors address concerns about ...interpretivist research regarding validity, reliability, objectivity, generalizability, and communicability of results that militate against its more widespread acceptance. Following the nonfoundationalist argument that all observation is theory-laden, context specific, and that there are no external criteria against which to assess research design and execution and the data produced, the authors propose that quality must be internalized within the underlying research philosophy rather than something to be tested upon completion. This requires a shift from the notion of validity as an outcome to validation as a process. To elucidate this, they provide a guiding framework and present a case illustration that will assist an interpretivist entrepreneurship researcher to establish and demonstrate the quality of their work.
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NUK, OILJ, SAZU, UKNU, UL, UM, UPUK
Horses were domesticated from the Eurasian steppes 5,000-6,000 years ago. Since then, the use of horses for transportation, warfare, and agriculture, as well as selection for desired traits and ...fitness, has resulted in diverse populations distributed across the world, many of which have become or are in the process of becoming formally organized into closed, breeding populations (breeds). This report describes the use of a genome-wide set of autosomal SNPs and 814 horses from 36 breeds to provide the first detailed description of equine breed diversity. F(ST) calculations, parsimony, and distance analysis demonstrated relationships among the breeds that largely reflect geographic origins and known breed histories. Low levels of population divergence were observed between breeds that are relatively early on in the process of breed development, and between those with high levels of within-breed diversity, whether due to large population size, ongoing outcrossing, or large within-breed phenotypic diversity. Populations with low within-breed diversity included those which have experienced population bottlenecks, have been under intense selective pressure, or are closed populations with long breed histories. These results provide new insights into the relationships among and the diversity within breeds of horses. In addition these results will facilitate future genome-wide association studies and investigations into genomic targets of selection.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Background and Aims
Patients with opioid use disorder (OUD) must be able to obtain prescribed buprenorphine/naloxone films (BUP/NX) and naloxone nasal spray (NNS) from a pharmacy promptly to reduce ...risk for a recurrence of use and subsequent morbidity and mortality. Telephone audits have identified concerning gaps in availability of NNS within US pharmacies, but the availability of BUP/NX has not been rigorously evaluated. This study estimated the availability of BUP/NX and NNS in the US state of Texas and compared availability by pharmacy type and metropolitan status.
Design
A cross‐sectional telephone audit with a secret shopper approach conducted from 18 May 2020 to 7 June 2020.
Setting and Participants
A random sample of 800 of 5078 (16%) community pharmacies licensed with the Texas State Board of Pharmacy.
Measurements
Primary outcomes included availability of a 1‐week supply of generic BUP/NX 8/2 mg films and a single unit of NNS 4 mg, overall and by pharmacy type. Secondary outcomes included willingness and estimated time‐frame to order BUP/NX if unavailable.
Findings
Data from 704 pharmacies (471 chain, 233 independent) were included for analyses. Of these, 34.1% of pharmacies (45.0% of chains versus 12.0% of independents, P < 0.0001) were willing and able to dispense a 1‐week supply of generic BUP/NX and a single unit of NNS. BUP/NX alone was available in 42.2% of pharmacies (52.4% of chains versus 21.5% of independents, P < 0.0001). NNS alone was available in 60.1% of pharmacies (77.9% of chains versus 24.0% of independents, P < 0.0001). Of the 397 pharmacies with generic BUP/NX unavailable, 62.2% of pharmacies (73.9% of chains versus 48.0% of independents, P < 0.0001) indicated willingness to order.
Conclusions
Most pharmacies in Texas do not appear to be willing and able to dispense prescribed buprenorphine/naloxone films and naloxone nasal spray to patients with opioid use disorder in a timely manner. Deficiencies in availability are markedly more pronounced in independent pharmacies compared with chain pharmacies.
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BFBNIB, DOBA, FSPLJ, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, SIK, UILJ, UKNU, UL, UM, UPUK, VSZLJ
Objective:
Recycling tenofovir and lamivudine/emtricitabine (XTC) with dolutegravir would provide a more tolerable, affordable, and scalable second-line regimen than dolutegravir with an optimized ...nucleoside reverse transcriptase inhibitor (NRTI) backbone. We evaluated efficacy of tenofovir/lamivudine/dolutegravir (TLD) in patients failing first-line tenofovir/XTC/efavirenz or nevirapine.
Design:
Single arm, prospective, interventional study.
Setting:
Two primary care clinics in Khayelitsha, South Africa.
Participants:
Sixty adult patients with two viral loads greater than 1000 copies/ml.
Intervention:
Participants were switched to TLD with additional dolutegravir (50 mg) for 2 weeks to overcome efavirenz induction.
Primary outcome:
Proportion achieving viral load less than 50 copies/ml at week 24 using the FDA snapshot algorithm.
Results:
Baseline median CD4
+
cell count was 248 cells/μl, viral load 10 580 copies/ml and 48 of 54 (89%) had resistance (Stanford score ≥15) to one or both of tenofovir and XTC. No participants were lost to follow-up. At week 24, 51 of 60 85%, 95% confidence interval (CI) 73–93% were virologically suppressed, six had viral load 50–100 copies/ml, one had viral load 100–1000 copies/ml, one no viral load in window, and one switched because of tenofovir-related adverse event. No integrase mutations were detected in the one participant meeting criteria for resistance testing. Virological suppression was achieved by 29 of 35 (83%, 95% CI 66–93%) with resistance to tenofovir and XTC, 11 of 13 (85%, 95% CI 55–98%) with resistance to XTC, and six of six (100%, 95% CI 54–100%) with resistance to neither.
Conclusion:
A high proportion of adults switching to second-line TLD achieved virologic suppression despite substantial baseline NRTI resistance and most not suppressed had low-level viraemia (≤100 copies/ml). This suggests recycling tenofovir and XTC with dolutegravir could provide an effective second-line option.
•Potent synthetic opioids are the primary driver of drug overdose deaths in the U.S.•Increasingly potent, long-acting opioid antagonists are being developed in response.•Evidence does not support the ...hypothesized need for these formulations.•Adoption of these formulations could have unintended consequences.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Abstract Cannabis sativa has been associated with contradictory effects upon seizure states despite its medicinal use by numerous people with epilepsy. We have recently shown that the ...phytocannabinoid cannabidiol (CBD) reduces seizure severity and lethality in the well-established in vivo model of pentylenetetrazole-induced generalised seizures, suggesting that earlier, small-scale clinical trials examining CBD effects in people with epilepsy warrant renewed attention. Here, we report the effects of pure CBD (1, 10 and 100 mg/kg) in two other established rodent seizure models, the acute pilocarpine model of temporal lobe seizure and the penicillin model of partial seizure. Seizure activity was video recorded and scored offline using model-specific seizure severity scales. In the pilocarpine model CBD (all doses) significantly reduced the percentage of animals experiencing the most severe seizures. In the penicillin model, CBD (≥10 mg/kg) significantly decreased the percentage mortality as a result of seizures; CBD (all doses) also decreased the percentage of animals experiencing the most severe tonic–clonic seizures. These results extend the anti-convulsant profile of CBD; when combined with a reported absence of psychoactive effects, this evidence strongly supports CBD as a therapeutic candidate for a diverse range of human epilepsies.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
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