Changes in emergency department use in British Columbia, Canada, during the first 3 years of the COVID-19 pandemic.

BACKGROUND: Previous studies have shown reductions in the volume of emergency department visits early in the COVID-19 pandemic, but few have evaluated the pandemic's impact over time or stratified analyses by reason for visits. We aimed to quantify such changes in British Columbia, Canada, cumulatively and during prominent nadirs, and by reason for visit, age and acuity. METHODS: We included data from the National Ambulatory Care Reporting System for 30 emergency departments across BC from January 2016 to December 2022. We fitted generalized additive models, accounting for seasonal and annual trends, to the monthly number of visits to estimate changes throughout the pandemic, compared with the expected number of visits in the absence of the pandemic. We determined absolute and relative differences at various times during the study period, and cumulatively since the start of the pandemic until the overall volume of emergency department visits returned to expected levels. RESULTS: Over the first 16 months of the pandemic, the volume of emergency department visits was reduced by about 322 300 visits, or 15% (95% confidence interval 12%-18%), compared with the expected volume. A sharp drop in pediatric visits accounted for nearly one-third of the reduction. The timing of the return to baseline volume of visits differed by subgroup. The largest and most sustained decreases were in respiratory-related emergency department visits, visits among children, visits among oldest adults and non-urgent visits. Later in the pandemic, we observed increased volumes of highest-urgency visits, visits among children and visits related to ear, nose and throat. INTERPRETATION: We have extended evidence that the impact of the COVID-19 pandemic and associated mitigation strategies on emergency department visits in Canada was substantial. Both our findings and methods are relevant in public health surveillance and capacity planning for emergency departments in pandemic and nonpandemic times.

Short-term exposure to ambient air pollution and individual emergency department visits for COVID-19: a case-crossover study in Canada.

BACKGROUND: Ambient air pollution is thought to contribute to increased risk of COVID-19, but the evidence is controversial. OBJECTIVE: To evaluate the associations between short-term variations in outdoor concentrations of ambient air pollution and COVID-19 emergency department (ED) visits. METHODS: We conducted a case-crossover study of 78 255 COVID-19 ED visits in Alberta and Ontario, Canada between 1 March 2020 and 31 March 2021. Daily air pollution data (ie, fine particulate matter with diameter less than 2.5 µm (PM2.5), nitrogen dioxide (NO2) and ozone were assigned to individual case of COVID-19 in 10 km × 10 km grid resolution. Conditional logistic regression was used to estimate associations between air pollution and ED visits for COVID-19. RESULTS: Cumulative ambient exposure over 0-3 days to PM2.5 (OR 1.010; 95% CI 1.004 to 1.015, per 6.2 µg/m3) and NO2 (OR 1.021; 95% CI 1.015 to 1.028, per 7.7 ppb) concentrations were associated with ED visits for COVID-19. We found that the association between PM2.5 and COVID-19 ED visits was stronger among those hospitalised following an ED visit, as a measure of disease severity, (OR 1.023; 95% CI 1.015 to 1.031) compared with those not hospitalised (OR 0.992; 95% CI 0.980 to 1.004) (p value for effect modification=0.04). CONCLUSIONS: We found associations between short-term exposure to ambient air pollutants and COVID-19 ED visits. Exposure to air pollution may also lead to more severe COVID-19 disease.

Meta-analysis of multi-jurisdictional health administrative data from distributed networks approximated individual-level multivariable regression.

BACKGROUND AND OBJECTIVES: Compare meta-analysis in a distributed network to individual-level analysis for assessment of time trends of health services utilization with health administrative data. METHODS: We used administrative data from Ontario, Canada to analyze temporal trends in pediatric inflammatory bowel disease health services use. Beta coefficients were obtained using negative binomial, logistic, and Cox proportional hazards regression models. We replicated the individual-level analyses in each Ontario Local Health Integration Network (LHIN), then meta-analyzed aggregate trends using both fixed and random effects meta-analysis. We compared the pooled estimates of effect with individual-level analysis. RESULTS: Beta coefficients, summary effect estimates, and 95% confidence intervals (CIs) from the meta-analysis of data from distributed networks were not different than those from individual-level data, regardless of meta-analytic approach used. For example, the 5-year odds ratio of colectomy in ulcerative colitis using individual-level analysis was 0.978 (95% CI 0.950 to 1.007) compared to distributed network fixed effects meta-analysis: 0.982 (95% CI 0.950 to 1.015), and random effects meta-analysis: 0.982 (95% CI 0.950 to 1.015). CONCLUSION: Meta-analysis of multi-jurisdictional estimates were similar to estimates obtained from individual-level analysis. This method is a valid alternative for analysis of multi-jurisdictional data when individual-level data cannot be shared.

Air quality in Canadian port cities after regulation of low-sulphur marine fuel in the North American Emissions Control Area.

Large marine vessels have historically used high-sulphur (S) residual fuel oil (RFO), with substantial airborne releases of sulphur dioxide (SO2) and fine particulate matter (PM2.5) enriched in vanadium (V), nickel (Ni) and other air pollutants. To address marine shipping air pollution, Canada and the United States have jointly implemented a North American Emissions Control Area (NA ECA) within which ships are regulated to use lower-sulphur marine fuel or equivalent SO2 scrubbers (i.e., 3.5% maximum fuel S reduced to 1% S in 2012 and 0.1% S in 2015). To investigate the effects of these regulations on local air quality, we examined changes in air pollutant (SO2, PM2.5, NO2, O3), and related PM2.5 components (V, Ni, sulphate) concentrations over 2010-2016 at the Canadian port cities of Halifax, Vancouver, Victoria, Montreal, and Quebec City. SO2 concentrations showed large statistically significant decreases at all sites (-28% to -83% mean hourly change), with the largest improvements in the coastal cities when the 0.1% fuel S regulation took effect. Statistically significant PM2.5 but smaller fractional reductions were also observed (-7% to -37% mean hourly change), reflecting the importance of non-marine PM sources. RFO marker species V and Ni in PM2.5 dramatically declined following regulation implementation, consistent with decreased RFO use likely indicating the switch to low-S distillate fuel oil rather than exhaust scrubbers for initial compliance. Significant changes in other pollutants with non-marine sources (NO2, O3) were not contemporaneous with the regulatory timeline. The large SO2 improvements in the port cities have reduced 1-h concentrations to <30 ppb, comparable to Canadian urban locations with few local SO2 sources and likely reducing health risks to susceptible populations such as asthmatics and the elderly. Our findings indicate that the implementation of the NA ECA improved air quality at Canadian port cities immediately following the requirement for lower-S fuel. These air quality improvements suggest that large-scale international benefits can result from implementation of the 2020 global low-S marine fuel regulations.

Shifting Health Care Use from Hospitalisations and Surgeries to Outpatient Visits in Children with Inflammatory Bowel Disease: A Population-based Cohort Study from Ontario, Canada.

BACKGROUND: Modern, specialised care for children with inflammatory bowel disease [IBD] may have resulted in changes in health services use. We report trends over time in health services utilisation and surgery for children with IBD and children without IBD. METHODS: Children aged <18 years, diagnosed with IBD between 1994 and 2013 [n = 5518] and followed until 2015 in Ontario, Canada, were identified from health administrative data and matched to children without IBD on age, sex, rural/urban household, and income [n = 26,677]. We report the annual percentage change [APC] with 95% confidence intervals [CI] in the rate of outpatient visits, emergency department [ED] visits, and hospitalisations, using negative binomial regression for events within 5 years from the diagnosis/index date. We used Cox proportional hazards regression models to report APC in hazards of intestinal resection [Crohn's disease; CD] and colectomy [ulcerative colitis; UC]. RESULTS: IBD-specific hospitalisation rates decreased by 2.5% [95% CI 1.8-3.2%] annually, and all-cause hospitalisation rates in children without IBD decreased by 4.3% [95% CI 3.5-5.1%] annually. Intestinal resection risk in CD decreased by 6.0% [95% CI 4.6-7.3%] annually and colectomy risk in UC decreased by 3.0% [95% CI 0.7-5.2%] annually. In contrast, IBD-specific outpatient visit rates increased after 2005 by 4.0% [95% CI 3.1-4.9%] annually. Similar trends in outpatient visits were not observed in children without IBD. CONCLUSIONS: Hospitalisations and surgeries decreased over time while outpatient visits increased after 2005. Decreasing hospitalisations were mirrored in children without IBD, likely resulting from a combination of changes in disease management and health system factors.

Selective Inhibition of CBX6: A Methyllysine Reader Protein in the Polycomb Family.

The polycomb paralogs CBX2, CBX4, CBX6, CBX7, and CBX8 are epigenetic readers that rely on "aromatic cage" motifs to engage their partners' methyllysine side chains. Each CBX carries out distinct functions, yet each includes a highly similar methyllysine-reading chromodomain as a key element. CBX7 is the only chromodomain that has yet been targeted by chemical inhibition. We report a small set of peptidomimetic agents in which a simple chemical modification switches the ligands from one with promiscuity across all polycomb paralogs to one that provides selective inhibition of CBX6. The structural basis for this selectivity, which involves occupancy of a small hydrophobic pocket adjacent to the aromatic cage, was confirmed through molecular dynamics simulations. Our results demonstrate the increases in affinity and selectivity generated by ligands that engage extended regions of chromodomain binding surfaces.

Structure-Activity Relationships of Cbx7 Inhibitors, Including Selectivity Studies against Other Cbx Proteins.

The five human polycomb (Pc) paralog proteins, chromobox homolog (Cbx) 2/4/6/7/8, are a family of chromodomain containing methyllysine reader proteins that are canonical readers of trimethyllysine 27 on histone 3 (H3K27me3). The aberrant expression of the Cbx7 gene is implicated in several cancers including prostate, gastric, thyroid, pancreas, and colon cancer. Previous reports on antagonizing the molecular recognition of Cbx7-H3K27me3 with chemical inhibitors showed an impact on prostate cancer cell lines. We report here on the design, synthesis, and structure-activity relationships of a series of potent peptidomimetic antagonists that were optimized on a trimethyllysine-containing scaffold to target Cbx7. The ligands were characterized using fluorescence polarization (FP) for their binding efficiency and selectivity against the Pc paralog Cbx proteins. The most selective ligand 9, as indicated by the FP data analysis, was further characterized using the isothermal titration calorimetry (ITC). Compound 9 exhibits a 220 nM potency for Cbx7 and exhibits 3.3, 1.8, 7.3 times selective for Cbx7 over Cbx2/4/8 and 28-fold selective over the HP1 family member Cbx1. Our research provides several potent and partially selective inhibitors for Cbx2/4/7 that do not contain trimethyllysine. Our models and binding data suggest that the aromatic cages of Cbx7/Cbx4 can accommodate larger alkyl groups such as diisobutyl substitution on the lysine nitrogen.