Burnaby Hospital

Chang et al. [1] report on demographics, causes of death and other significant conditions among people who had opioids and/or stimulants detected in their unintentional acute drug toxicity death between 2013 and 2023. We have published similar analyses to distinguish chronic disease diagnoses and health service visits before death for decedents in British Columbia (BC), Canada, with opioids and/or stimulants deemed relevant to death [2]. Chang et al.’s [1] inclusion of non-substance–related contributors to death derived from death certificates fills a critical gap in the literature, as prior analyses (to our knowledge) have not examined how such contributing causes differ by opioid and/or stimulant detection. Although our analyses identified chronic disease diagnoses that may have contributed to death, we did not adjudicate these as contributing causes. Consistent with Chang et al., [1] we identified cardiovascular disease (CVD) as most prevalent among stimulant-only toxicity deaths, suggesting that some stimulant-related deaths may result from acute complications of chronic disease exacerbated by stimulant use. In our analysis, the stimulant toxicity group had higher rates of musculoskeletal, circulatory, respiratory and cardiovascular disease, however, after adjusting for age, only CVD remained associated with stimulant-only deaths. In contrast, in Chang et al.’s [1] study, associations between chronic disease and stimulant-toxicity death persisted after age-adjustment. One explanation is that drug toxicity triggered or exacerbated undiagnosed or acute conditions captured on death certificates, but not identified through prior diagnoses in administrative health data. As such, Chang et al.’s [1] integration of contributing causes of death strengthens and extends existing hypotheses regarding the role of chronic disease in stimulant-related mortality and affirms the findings of recent studies, which have identified rising rates of stimulant-involved CVD mortality in the past decade in the United States [3, 4]. As stimulants are increasingly relevant in drug poisoning deaths in BC—increasing from 68% in 2015 to approximately 80% in 2024 [5]—it is important to distinguish stimulant-only from stimulant-involved mortality to develop effective, tailored strategies for polysubstance users. One promising finding in our study was that over 60% of decedents had a health service visit in the year before death, suggesting a potential intervention point at which tailored services could be offered, such as treatments to address CVD and/or reduce exposure to illicit stimulants [6]. Heather Palis: Conceptualization; writing—original draft; writing—review and editing. Jennifer Vincent: Writing—original draft; writing—review and editing; conceptualization. Juls Budau: Writing—review and editing; writing—original draft; conceptualization. Kevin Hu: Conceptualization; writing—original draft; writing—review and editing. Andrew Tu: Conceptualization; writing—original draft; writing—review and editing. None.

Chrysin is a dietary flavonoid with antioxidant and anti-inflammatory activity, but its clinical potential is limited by poor oral bioavailability. This randomized double-blind three period crossover trial evaluated the pharmacokinetics of a novel micellar chrysin formulation co-encapsulated with quercetin and rutin (LMC) compared with a non-micellar chrysin formulation (NMC) and unformulated chrysin (UFC). Secondary objectives included in vitro permeability (Caco-2) and a 30-day safety assessment of daily LMC supplementation. Sixteen healthy adults received a single oral dose of each formulation in randomized order separated by a 7-day washout. Plasma chrysin was quantified over 24 h to determine pharmacokinetic parameters. In vitro Caco-2 assays evaluated permeability, and clinical biochemistry of 15 participants were assessed weekly during 30 days of daily LMC use. LMC achieved >2-fold higher systemic exposure than unformulated chrysin (AUC0–24 = 914.8 ± 697.5 ng·h/mL; Cmax = 87.3 ± 59.4 ng/mL; both p < 0.05) and >2.6-fold higher than NMC, supported by >10-fold higher in vitro permeability. Daily LMC supplementation was well tolerated, with only mild, reversible adverse events and no clinically relevant safety changes, despite higher systemic exposure. Small, but significant, reductions in fasting glucose were observed in both sexes. The novel micellar chrysin–quercetin–rutin formulation substantially improved bioavailability and was well tolerated during 30 days of daily use, supporting its potential as an advanced delivery strategy for flavonoids with poor oral absorption and identifying glucose regulation as a physiological effect of interest.

In this study, we address the challenges of non-convex optimization in neural networks (NNs) by formulating the training of multilayer perceptron (MLP) NNs as a difference of convex functions (DC) problem. Utilizing the basic convex–concave algorithm to solve our DC problems, we introduce two alternative optimization techniques, <italic xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">DC-GD</i> and <italic xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">DC-OPT</i>, for determining MLP parameters. By leveraging the non-uniqueness property of the convex components in DC functions, we generate strongly convex components for the DC NN cost function. This strong convexity enables our proposed algorithms, <italic xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">DC-GD</i> and <italic xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">DC-OPT</i>, to achieve an <italic xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">iteration complexity</i> of <inline-formula xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink"><tex-math notation="LaTeX">$O\left(\log \left(\frac{1}{\varepsilon }\right)\right)$</tex-math></inline-formula>, surpassing that of other solvers, such as stochastic gradient descent (<italic xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">SGD</i>), which has an <italic xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">iteration complexity</i> of <inline-formula xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink"><tex-math notation="LaTeX">$O\left(\frac{1}{\varepsilon }\right)$</tex-math></inline-formula>. This improvement raises the convergence rate from sublinear (<italic xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">SGD</i>) to linear (ours) while maintaining comparable <italic xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">total computational costs</i>. Furthermore, conventional NN optimizers like <italic xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">SGD</i>, <italic xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">RMSprop</i>, and <italic xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">Adam</i> are highly sensitive to the learning rate, adding computational overhead for practitioners in selecting an appropriate learning rate. In contrast, our <italic xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">DC-OPT</i> algorithm is hyperparameter-free (i.e., it requires no learning rate), and our <italic xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">DC-GD</i> algorithm is less sensitive to the learning rate, offering comparable accuracy to other solvers. Additionally, we extend our approach to a convolutional NN architecture, demonstrating its applicability to modern NNs. We evaluate the performance of our proposed algorithms by comparing them to conventional optimizers such as <italic xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">SGD</i>, <italic xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">RMSprop</i>, and <italic xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">Adam</i> across various test cases. The results suggest that our approach is a viable alternative for optimizing shallow MLP NNs.

Social prescribing is a model of care, usually in the community-setting, which aims to address people’s unmet social needs. Volunteers support primary health care and community-based care in non-medical roles. However, few studies focus on volunteers in social prescribing, therefore, aimed to synthesize the effect of health or peer volunteer-led interventions on psychosocial and behavioural outcomes for middle-aged and older adults with Type 2 Diabetes Mellitus (T2DM) to inform future work for volunteering in social prescribing. We followed Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines and searched six databases and Google Scholar for peer-reviewed studies from 2013+ (last search May 16, 2024). We included randomized controlled trials (RCTs) from all languages, and synthesized data using the Cochrane’s Synthesis Without Meta-analysis (SWiM) guidelines; and assessed risk of bias using the "Risk of Bias 2 Tool". We identified nine RCTs (reported in 10 publications). Interventions aimed to promote self-management of T2DM, and study duration ranged from one to 46 months. Training for volunteers varied between one to 32 hours, and most volunteers were offered a stipend. For psychosocial outcomes, only one outcome on social support favoured the intervention group, with the remaining outcomes reporting no differences between study groups. For behaviour, six outcomes (from three studies) favoured the intervention group, and for three outcomes there were no differences between study groups. In conclusion, volunteers bring a unique perspective to health interventions, but volunteer training, matching and retention, as well as intervention mode and duration, and geographical context need to be thoughtfully considered as important implementation factors. This work generates ideas for future studies focused on volunteers and T2DM management and social prescribing.Trial registration: PROSPERO registration:CRD42023453506.

Background.Because M. tuberculosis evolves slowly, transmission clusters often contain multiple individuals with identical consensus genomes, making it difficult to reconstruct transmission chains. Finding additional sources of shared M. tuberculosis variation could help overcome this problem. Previous studies have reported M. tuberculosis diversity within infected individuals; however, whether within-host variation improves transmission inferences remains unclear.Methods.To evaluate the transmission information present in within-host M. tuberculosis variation, we re-analyzed publicly available sequence data from three household transmission studies, using household membership as a proxy for transmission linkage between donor-recipient pairs.Findings.We found moderate levels of minority variation present in M. tuberculosis sequence data from cultured isolates that varied significantly across studies (mean: 6, 7, and 170 minority variants above a 1% minor allele frequency threshold, outside of PE/PPE genes). Isolates from household members shared more minority variants than did isolates from unlinked individuals in the three studies (mean 98 shared minority variants vs. 10; 0.8 vs. 0.2, and 0.7 vs. 0.2, respectively). Shared within-host variation was significantly associated with household membership (OR: 1.51 [1.30,1.71], for one standard deviation increase in shared minority variants). Models that included shared within-host variation improved the accuracy of predicting household membership in all three studies as compared to models without within-host variation (AUC: 0.95 versus 0.92, 0.99 versus 0.95, and 0.93 versus 0.91).Interpretation.Within-host M. tuberculosis variation persists through culture and could enhance the resolution of transmission inferences. The substantial differences in minority variation recovered across studies highlights the need to optimize approaches to recover and incorporate within-host variation into automated phylogenetic and transmission inference.FundingNIAID: 5K01AI173385

Patients seen by the palliative care team often have difficult and intractable symptoms. The current standard of practice to manage these symptoms is the deeply sedating midazolam continuous subcutaneous infusion for patients who are expected to expire within hours to days. Dexmedetomidine provides sedation but lacks evidence in palliative care use. This study describes continuous subcutaneous infusion of dexmedetomidine's effect on refractory pain and delirium. Retrospective, observational chart review and conducted in accordance with SQUIRE (quality improvement study). Twenty adult patients (18 years of age or older) with metastatic cancer disease admitted to three palliative complex care units of Fraser Health who received continuous subcutaneous infusion of dexmedetomidine between January 2017 to August 31, 2019. Average length of dexmedetomidine use was 9 days (1/3 length of stay). Eight of the 13 patients with pain symptoms exhibited an overall decline in pain. Four of the 6 patients with delirium had an initial decrease in delirium, but it did not last beyond the first day. Despite progressive clinical deterioration, adjunctive medications decreased or remained the same for 53% of as needed medications and 65% for regularly scheduled medications. Forty-five percent of patients had ≥50% days of rousable sedation. Hypotension occurred in 85% of patients. Dexmedetomidine provided benefit in managing intractable pain while allowing patients to remain rousable, but only had a short effect on delirium symptoms.

Metro Vancouver’s Sperling Avenue Forcemain cuts right through environmentally sensitive Burnaby Lake Park. The 533 mm diameter steel force main was installed in 1962 and is a critical piece of Metro Vancouver’s wastewater system. In 2020, Metro Vancouver issued an RFP for condition assessment of the force main and selected Pure Technologies to execute a high-resolution condition assessment. Prior to the project, no previous condition assessments had been completed; however, the force main suffered from point failures in the past. In 2021, an inspection of the force main was completed with a high-resolution, free-swimming inspection technology. Challenges associated with the inspection included limited flow control ability and mobilizing and working during the COVID-19 pandemic. Analysis of the inspection data identified defects, which Metro Vancouver decided to repair. In September 2022, repairs were completed, increasing Metro Vancouver’s confidence the force main can continue to successfully operate in its unique in situ conditions.

We erect the Cenocimbicinae, a new subfamily of Cimbicidae (Hymenoptera, Symphyta), restricted to the Selandian Menat Formation of France, the oldest occurrence of the family, and the Ypresian Okanagan Highlands of far-western North America. We describe new taxa from the Okanagan Highlands: Allenbycimbex morrisae gen. et sp. nov. and Leptostigma n. gen. with seven new species: L. alaemacula n. sp., L. brevilatum n. sp., L. fasciatum n. sp., L. longiclava n. sp., L. longipallidum n. sp., L. longitenebricum n. sp., and L. proxivena n. sp. We revise the Cimbicidae from the Ypresian Green River Formation and the Priabonian Florissant Formation, both in Colorado, USA. The oldest fossil of a modern cimbicid subfamily appears with a single pachylostictine specimen in the Green River Formation, and all Cimbicidae are in modern subfamilies after the Ypresian (we did not examine one larva known from Priabonian Baltic amber). Pseudocimbex clavatus Rohwer 1908 from the Florissant Formation is not a cimbicid; we treat it as Tenthredinoidea incertae sedis. We transfer Cimbex vetusculus Cockerell to Floricimbex n. gen.