Factors associated with patient perceived suboptimal dosing of in-hospital opioid agonist therapy among people who use illicit drugs in Vancouver, Canada.

Optimal dosing of opioid agonist therapy (OAT) is essential for treatment success. However, initiation and maintenance of OAT in hospital settings can be challenging given differing levels of opioid tolerance, withdrawal, and intoxication among patients.The objective of this study was to characterize the prevalence and factors associated with in-hospital patient perceived suboptimal OAT dosing among people who use illicit drugs (PWUD) in Vancouver, Canada.Data were derived from three prospective cohorts of PWUD in Vancouver, Canada. Bivariable and multivariable logistic regression models were used to examine factors associated with patient perceived suboptimal in-hospital OAT dose.273 study participants were prescribed OAT while in hospital: 83 (30.4%) participants perceived their OAT dose to be suboptimal. In a multivariable model, factors positively associated with a perceived suboptimal OAT dose included: homelessness (adjusted odds ratio [AOR] = 2.85; 95% CI: 1.53-5.28), daily stimulant use (AOR = 2.03; 95% CI: 1.14-3.63) and illicit drug use while in hospital (AOR = 2.33; 95% CI: 1.31-4.16).Almost one third of participants perceived receiving a suboptimal OAT dose while in hospital. These observed correlations indicate that a patient's perception of suboptimal OAT dosing in hospital may be more prevalent for patients who are homeless, report polysubstance use with stimulants and opioids and who obtain illicit drugs while hospitalized. While cautious prescribing of OAT in patients experiencing hospitalization is important, these findings demonstrate a high prevalence of and apparent risk factors for perceived suboptimal OAT dosing.

Migration Patterns from an Open Illicit Drug Scene and Emergency Department Visits among People Who Use Illicit Drugs in Vancouver, Canada.

BACKGROUND: People who use illicit drugs (PWUD) experience various adverse health outcomes leading to increased healthcare service utilization. PWUD are also a highly mobile population which poses challenges to healthcare delivery. The objective of this study was to identify migration patterns from the Downtown Eastside (DTES), an urban illicit drug scene in Vancouver and to estimate the impact of different migration patterns on two outcomes: a) emergency department (ED) visits and b) ED visits resulting in inpatient admission among PWUD. METHODS: Three prospective cohorts of PWUD in Vancouver were linked with regional ED data. We defined the optimal number of trajectory groups that best represented distinct patterns of migration from Vancouver's DTES using a latent class growth analysis. Then, generalized estimating equations were used to estimate the effect of migration patterns on the two ED outcomes. RESULTS: Four distinct migration trajectory patterns were identified among the 1210 included participants: PWUD who consistently lived in the DTES, those who migrated out of DTES early, those who migrated out of DTES late, and those who frequently revisited the DTES. Participants who frequently revisited the DTES had higher odds of an ED visit (adjusted odds ratio = 1.62; 95% confidence interval: 1.28-2.06). There was no significant association between migration patterns and inpatient admission. CONCLUSIONS: We found that PWUD who frequently revisited the DTES were more likely to have utilized the ED, suggesting that there may be a subgroup of PWUD who are at increased risk of experiencing negative health outcomes.Supplemental data for this article is available online at 10.1080/10826084.2021.1958849.

The impact of high-dose opioid prescription on mortality rates among people living with HIV: A retrospective cohort study.

OBJECTIVES: High-dose opioid use is associated with increased morbidity, mortality, and healthcare utilization. People living with HIV (PLHIV) are frequently prescribed these medications to manage their pain. However, little is known about the relationship between being prescribed high doses of opioids (> 90 MME/d) and mortality risk among this population. The objective of this study was to examine the trends in mortality and the relationship between high-dose opioid analgesic prescribing and mortality among PLHIV. METHODS: Utilizing the STOP HIV/AIDS cohort--a population-level linked database of treatment of PLHIV in British Columbia--we conducted bivariable and multivariable generalized estimating equation (GEE) models with a Poisson distribution to examine the relationship between high-dose opioid prescription and all-cause mortality rates in the study sample. RESULTS: Between 1996 and 2015, 9272 PLHIV were included in the study. Age- and sex-adjusted mortality rate (using the 2011 Canadian population as the reference) was 30.99 per 1000 person-years (95% confidence interval [CI]: 28.11-33.88). In a multivariable GEE model with adjustment for various demographic and clinical confounders, there was a positive and independent association between being prescribed high-dose opioids and all-cause mortality rates (adjusted rate ratio [ARR] = 3.01; 95%CI: 2.47-3.66). DISCUSSION: We found that mortality rates were significantly higher among PLHIV who were prescribed high-dose opioids compared to those who were prescribed lower doses. Our results highlight the risk associated with the prescribing of high-dose opioids to manage HIV-related pain and emphasize the need to explore non-opioid approaches to pain management.

Gene Regulatory Networks for the Haploid-to-Diploid Transition of Chlamydomonas reinhardtii.

The sexual cycle of the unicellular Chlamydomonas reinhardtii culminates in the formation of diploid zygotes that differentiate into dormant spores that eventually undergo meiosis. Mating between gametes induces rapid cell wall shedding via the enzyme g-lysin; cell fusion is followed by heterodimerization of sex-specific homeobox transcription factors, GSM1 and GSP1, and initiation of zygote-specific gene expression. To investigate the genetic underpinnings of the zygote developmental pathway, we performed comparative transcriptome analysis of both pre- and post-fertilization samples. We identified 253 transcripts specifically enriched in early zygotes, 82% of which were not up-regulated in gsp1 null zygotes. We also found that the GSM1/GSP1 heterodimer negatively regulates the vegetative wall program at the posttranscriptional level, enabling prompt transition from vegetative wall to zygotic wall assembly. Annotation of the g-lysin-induced and early zygote genes reveals distinct vegetative and zygotic wall programs, supported by concerted up-regulation of genes encoding cell wall-modifying enzymes and proteins involved in nucleotide-sugar metabolism. The haploid-to-diploid transition in Chlamydomonas is masterfully controlled by the GSM1/GSP1 heterodimer, translating fertilization and gamete coalescence into a bona fide differentiation program. The fertilization-triggered integration of genes required to make related, but structurally and functionally distinct organelles-the vegetative versus zygote cell wall-presents a likely scenario for the evolution of complex developmental gene regulatory networks.