BACKGROUND:Vaccination helps prevent SARS-CoV-2 infection and severe COVID-19. However, vaccine-induced humoral immune responses vary among individuals and wane over time. We aimed to describe the SARS-CoV-2 anti-spike IgG antibody response to vaccination and identify health and demographic factors associated with this response among children and adults. METHODS:We studied a subset of double-vaccinated children (n = 151; mean age: 12 ± 1.5 years, 46% female) and adults (n = 995; 44 ± 6.0 years, 60% female) from the cross-provincial Canadian CHILD Cohort. Dried blood spots were collected over two time periods (March 2021 to September 2021; October 2021 to January 2022). Antibody levels were quantified using automated chemiluminescent ELISAs. Demographic, vaccination, and health data (e.g. location, age, ethnicity, prior SARS-CoV-2 infection, vaccine type, comorbidities) were collected via online questionnaires. Associations were tested using multivariable linear mixed-effect analysis accounting for household membership. RESULTS:Our cohort had SARS-CoV-2 anti-spike seropositivity rate of 97% following two COVID-19 vaccine doses. In both children and adults, the highest antibody levels were observed around three months post-vaccination and did not differ by biological sex. Higher antibody levels were associated with: prior SARS-CoV-2 infection (β = 0.16 scaled luminescence units; 95%CI 0.07,0.25), age < 18 years (13-17 years old, β = 0.14; 95%CI 0.03,0.25 | <13 years old: β = 0.17; 95%CI 0.03,0.32) and receiving mRNA vaccines (two Moderna: β = 0.21; 95%CI 0.10,0.33 | two Pfizer-BioNTech (β = 0.10; 95%CI 0.02,0.18 | one Modern and one Pfizer-BioNTech β = 0.14; 95%CI 0.01,0.27) vs. receiving Oxford-AstraZeneca viral vector vaccines. There were no antibody level differences among study sites, ethnicities, household essential worker status, education levels, immunosuppressive comorbidity presence, or when comparing a 3-8 vs. 9-16-week interval between vaccine doses. INTERPRETATION:We identified key factors (i.e. prior SARS-CoV-2 infection, age, vaccine type) associated with post-vaccination antibody responses in children and adults across Canada. This may help improve future vaccine development and deployment among different population subgroups.

OBJECTIVE:To examine the epidemiology and follow-up of reported blood and body fluid exposures (BBFEs) from 2013-2023 in one health region in Canada. METHODS:BBFE incidents reported in a provincial workplace health database were identified either through database coding or by linking laboratory blood-test results with corresponding incident reports. Follow-up was assessed using post-exposure blood testing records in the database. RESULTS:Of the 27,760 total workplace incident reports, 3,687 were included as BBFEs (17.1/1,000 person-years), with the highest rates in resident physicians and a progressive decline with age. Although no seroconversions were documented, even among BBFE cases from anti-HCV-positive and HIV-positive sources, complete follow-up was only documented in 28.9% and 36.4% of cases respectively. CONCLUSION:Ensuring complete documentation and timely follow-up are critical to properly assessing risk and preventing bloodborne disease.

Understanding if and how vaccination attitudes are shared among family members can help inform strategies to increase uptake. We assessed the correlation of self-reported COVID-19 vaccination attitudes and uptake among Canadian children and their parents, and investigated predictors of parents’ attitudes in January 2021–2022. We studied a subset of 1458 CHILD Cohort Study households where children and parents self-reported their adherence to COVID-19 safety practices, vaccine attitudes and uptake, and health status during the pandemic. Vaccine hesitancy was defined as intending to not receive a COVID-19 vaccine. We identified predictors for vaccine hesitancy using regression and machine learning models and assessed agreement in vaccine intentions between parent–child responses. About 4

Background Migrants represent a diverse population whose unique experiences and healthcare barriers may influence antibiotic prescribing. This study examined the appropriateness of outpatient antibiotic prescriptions and determinants of inappropriate prescriptions among migrants in British Columbia, Canada.Methods We conducted a population-based retrospective cohort study using health administrative databases. Antibiotic prescriptions were classified as appropriate, potentially appropriate, never appropriate, or unknown for migrants and non-migrants based on physician billing diagnostic codes. We used multivariable ordinal regression models to identify the determinants of antibiotic prescription appropriateness in 2022.Results From 2000 to 2022, the overall outpatient antibiotic prescribing rates declined by 45.3% in migrants and by 42.7% in non-migrants. Migrants had a higher proportion of never-appropriate prescriptions and a lower proportion of appropriate prescriptions than non-migrants. After adjustment for patient and prescriber factors, migrants were associated with less appropriate prescribing than non-migrants (odds ratio [OR] 1.12, 95% CI 1.11-1.13) in 2022. More than half of migrant prescription episodes were in the 35-64 years age group and were more likely to receive care from higher-volume physicians who were, on average, slightly older. Inappropriate prescribing was more likely among younger patients (0-11 versus 65+ years: OR 1.10, 95% CI 1.08-1.12), lower-income groups (lowest versus highest quintile: OR 1.04, 95% CI 1.03-1.05), and prescriptions from surgical (versus GP's: OR 1.38, 95% CI 1.31-1.45) and urological specialists (versus GP: OR 3.06, 95% CI 2.67-3.51).Conclusions While antibiotic prescribing appropriateness in BC has improved, inappropriate use remains common, particularly among the migrant population. Improving prescribing quality and equity requires strengthening stewardship in outpatient settings.

Objective To assess the appropriateness of outpatient antibiotic prescribing over a 24-year period. Methods We conducted a population-based retrospective cohort study using linked health administrative databases from 2000 to 2023 in Ontario, Canada. Oral antibiotic dispensations from the Ontario Drug Benefit Program were linked to physician billing claims. The study population included all adults aged >65 years. Prescription indication appropriateness was based on diagnostic codes from the clinician billings and categorized as Tier 1 (always), Tier 2 (sometimes), or Tier 3 (never appropriate). Proportional odds regression models, with random intercepts for physicians, were used to identify patient and prescriber characteristics associated with inappropriate antibiotic use for the year 2023. Results Between 2000 and 2023, overall antibiotic prescribing rates declined from 64 to 44 prescriptions per 100 person-years. The proportion of prescriptions classified as Tier 3 (never appropriate) also decreased, from 46.7% in 2000 to 37.3% in 2023. For Tier 1 conditions, antibiotic prescriptions increased from 10.6% to 13.1%, and for Tier 2, they increased from 13.9% to 21.4%. In 2023, multivariable regression models identified migrant status, male patient sex, younger patient age, physician male sex, international vs. Canadian medical degree, 25+ vs. <11 years since graduation, and median daily visits as independent predictors associated with less appropriate antibiotic prescribing. Conclusions We identified improvements in antibiotic prescribing among older adults in Ontario; however, substantial inappropriate prescribing persists. These findings can help set targets and priorities for antimicrobial stewardship interventions to improve outpatient prescribing quality and address disparities in care.

Background:Infant antibiotic use is associated with increased risk of asthma. We examined the population impact of antibiotic exposure in the first year of life on the burden of pediatric asthma in British Columbia, Canada, using simulation modeling.Methods:We performed a Bayesian meta-analysis of empirical studies to construct dose-response equations between antibiotic exposure in the first year of life and pediatric (<19 years of age) asthma. We used administrative health data to document trends in infant (< 1 year of age) antibiotic use in British Columbia during 2001 and 2018 (the study period). An independently developed microsimulation model of asthma was utilized to estimate asthma-related outcomes under three scenarios pertaining to the trends in antibiotic use during the study period: 1) observed trends, 2) flat trend in which the prescription rate remained at the 2001 value, and 3) intermediate trends midway between these two. We reported cumulative person-years with asthma, cumulative asthma incidence, and cumulative asthma exacerbations among the pediatric population during the study period.Results:There were 773,160 live births during the study period, with an average antibiotic prescription rate of 523 per 1,000 infants in the first year of life. The prescription rate decreased by 71.5% during the study period. In Scenario 1, there were 1,982,861 person-years with asthma, 183,392 asthma incident cases, and 383,072 exacerbations. Had the antibiotic exposure remained at the 2001 values (Scenario 2), there would have been additional 37,213 person-years with asthma, 10,053 asthma incident cases, and 23,280 exacerbations. Had the decline been half of the observed trend (Scenario 3), there would have been additional 20,318 person-years with asthma, 5,486 asthma incident cases, and 12,728 exacerbations. At least 80% of the excess burden in each outcome was attributable to the younger pediatric population of <10 years of age.Conclusions:The decline in infant antibiotic exposure has resulted in a substantial reduction in the burden of asthma in British Columbia. Such benefits should be considered when evaluating the value proposition of initiatives aimed at reducing unnecessary antibiotic exposure in early life.

Patients' expectations are a major contributor to the unnecessary prescribing of antibiotics, yet limited research has examined how physicians can calibrate these expectations. The studies we conducted tested how varying messages could impact patients' expectations for antibiotics and their experience of medical appointments. All the participants read a short scenario about an appointment for mild sinusitis symptoms, with the patient's expectation of antibiotics. In Study 1, the participants (n = 1069) were randomly assigned to read a positively framed, neutral, or negatively framed message regarding unnecessary antibiotics. In Study 2, the participants (n = 1073) read a message emphasizing either the societal or personal harms of unnecessary antibiotics, or a message without additional rationale. None of our pre-registered hypotheses were supported, but our exploratory analyses indicated that the societal message increased concern about antibiotic resistance. The participants who were more concerned about resistance were less likely to ask for antibiotics, more satisfied when the physician did not prescribe them, and more likely to recommend the physician to a friend. Discussing the consequences of the different courses of action did not appear to negatively impact physician-patient rapport. These studies demonstrate an inexpensive method with which to pre-test various messages about antibiotic consumption, and suggest that such messages are not negatively received by patients.

Posttranslational modifications can enhance immunogenicity of self-proteins. In several conditions, including hypertension, systemic lupus erythematosus, and heart failure, isolevuglandins (IsoLGs) are formed by lipid peroxidation and covalently bond with protein lysine residues. Here, we show that the murine class I major histocompatibility complex (MHC-I) variant H-2Db uniquely presents isoLG-modified peptides and developed a computational pipeline that identifies structural features for MHC-I accommodation of such peptides. We identified isoLG-adducted peptides from renal proteins, including sodium glucose transporter 2, cadherin 16, Kelch domain–containing protein 7A, and solute carrier family 23, that are recognized by CD8+ T cells in tissues of hypertensive mice, induce T cell proliferation in vitro, and prime hypertension after adoptive transfer. Finally, we find patterns of isoLG-adducted antigen restriction in class I human leukocyte antigens that are similar to those in murine analogs. Thus, we have used a combined computational and experimental approach to define likely antigenic peptides in hypertension.

Background: Urinary tract infections (UTI) are responsible for a significant portion of female, outpatient antibiotic prescriptions. Especially true in uncomplicated cases, where symptoms remain the cornerstone of diagnosis, ensuring the optimal choice of agent, dose, and duration may mitigate future bacterial resistance and lower the likelihood of adverse events and/or recurrence. This study is the first in Canada to examine the quality of antibiotic prescribing to females in the outpatient setting, for uncomplicated UTI–by agent, dose, and duration. Methods: All adult female residents of British Columbia with a physician record for cystitis from January 1, 2014, to December 31, 2018, were identified. Patients with a history of urologic abnormalities, spinal cord injury, catheter use, kidney transplant, as well as pregnant females, were excluded. Primary outcomes included the proportion of total episodes prescribed and the proportion of appropriate antibiotic use, examined using Poisson regression. Results: A total of 182,162 episodes of cystitis were examined, with 70% receiving an antibiotic prescription. The rate of cystitis-associated prescribing was 697 prescriptions per 1,000 population. Overall, 35% of prescriptions were appropriate by guideline adherence or clinical justification. Nitrofurantoin and trimethoprim-sulfamethoxazole, accounted for 71% of total antibiotic use. Seven days was the most commonly dispensed duration of therapy, followed by 5, then 10. Conclusions: Shortening length of therapy in line with clinical guidelines and encouraging the use of first line agents present clear, actionable targets for provincial stewardship efforts.

It is now apparent that immune mediators including complement, cytokines, and cells of the innate and adaptive immune system contribute not only to blood pressure elevation but also to the target organ damage that occurs in response to stimuli like high salt, aldosterone, angiotensin II, and sympathetic outflow. Alterations of vascular hemodynamic factors, including microvascular pulsatility and shear forces, lead to vascular release of mediators that affect myeloid cells to become potent antigen-presenting cells and promote T-cell activation. Research in the past 2 decades has defined specific biochemical and molecular pathways that are engaged by these stimuli and an emerging paradigm is these not only lead to immune activation, but that products of immune cells, including cytokines, reactive oxygen species, and metalloproteinases act on target cells to further raise blood pressure in a feed-forward fashion. In this review, we will discuss these molecular and pathophysiological events and discuss clinical interventions that might prove effective in quelling this inflammatory process in hypertension and related cardiovascular diseases.

While literature indicates that municipal rat management approaches are often unsuccessful, a lack of research comparing strategies makes the breadth of opportunities and challenges associated with different approaches uncertain. Here, we explored the municipal rat management policies and programs in seven cities in the United States of America. Rat policies were attained by collecting rat management-related municipal codes in each city. Information on rat programs was obtained through interviewing program stakeholders. Analysis followed a qualitative framework method to identify and describe themes associated with the structure and function of management approaches. Municipal codes served as a foundation for municipalities by outlining when, where, how, and by whom rat problems should be addressed. Programs employed the primary people responsible for performing on-the-ground management and they acted as a municipal "brain," organizing the city's strategy. We identify opportunities and barriers for other municipalities to consider in the design of their own rat management strategies.

Background Dentists in the United States and Canada have higher rates of prescribing broad-spectrum spectrum antibiotics than dentists in some other Western countries. The authors provide an overview of dental antibiotic prescribing trends from British Columbia, Canada. Methods The data include all prescriptions filed from pharmacies in British Columbia from 1996 through 2023. Dental antibiotic prescribing trends were explored visually and stratified according to patient-related characteristics, type of health service area, type of antibiotic, duration of therapy, and dentist’s experience. Interrupted time series regression analysis was conducted to investigate the impact of the COVID-19 pandemic on dental antibiotic prescribing. Results Dentistry accounted for an increasing proportion of overall antibiotic consumption in British Columbia. Dental prescriptions increased to a peak rate during the COVID-19 pandemic and remained elevated into 2023. The median duration of prescription converged toward a 7-day supply during the study period. Conclusions The authors documented how a decreasing trend in dental antibiotic prescribing prepandemic has been interrupted by means of continuously high rates after that event. Practical Implications Renewed efforts to ensure appropriateness of dental antibiotic prescribing are needed.

We describe a new species of green pitviper from southern and central parts of coastal Vietnam based on morphological and molecular (2406 bp from cyt b, ND4, and 16S rRNA mitochondrial DNA genes) lines of evidence. Trimeresurus cyanolabris sp. nov. is distinguished from its congeners by the combination of the following morphological characters: small size, maximum known SVL of 638 mm; dorsal scales in 21 (rarely 23)–21–15 rows, moderately keeled except the outermost rows; ventral scales 166–178; subcaudal scales 52–75, all paired; hemipenis forked, calyculate, reaching the 8th subcaudal; eye bright yellow in both sexes; dorsal surface deep green lacking cross-bands; postocular white stripe missing in both sexes; ventrolateral stripe faintly present on the first few dorsal scale rows in males, absent in females; throat, chin, and lower labials in shades of blue. The new species forms a distinct clade on the phylogenetic tree of the genus Trimeresurus and differs from the morphologically similar T. rubeus by a significant divergence in cytochrome b mitochondrial DNA gene sequences (p = 6.0%). The new species is currently known from low- to mid-elevations (ca. 90–400 m a.s.l.) in tropical forests of central-southern Vietnam. This discovery further underlines the importance of this area as a local center of herpetofaunal diversity and endemism, which is under great threat of deforestation.

Background Widespread human-to-human transmission of the severe acute respiratory syndrome coronavirus two (SARS-CoV-2) stems from a strong affinity for the cellular receptor angiotensin converting enzyme two (ACE2). We investigate the relationship between a patient’s nasopharyngeal ACE2 transcription and secondary transmission within a series of concurrent hospital associated SARS-CoV-2 outbreaks in British Columbia, Canada. Methods Epidemiological case data from the outbreak investigations was merged with public health laboratory records and viral lineage calls, from whole genome sequencing, to reconstruct the concurrent outbreaks using infection tracing transmission network analysis. ACE2 transcription and RNA viral load were measured by quantitative real-time polymerase chain reaction. The transmission network was resolved to calculate the number of potential secondary cases. Bivariate and multivariable analyses using Poisson and Negative Binomial regression models was performed to estimate the association between ACE2 transcription the number of SARS-CoV-2 secondary cases. Results The infection tracing transmission network provided n = 76 potential transmission events across n = 103 cases. Bivariate comparisons found that on average ACE2 transcription did not differ between patients and healthcare workers ( P = 0.86). High ACE2 transcription was observed in 98.6% of transmission events, either the primary or secondary case had above average ACE2 . Multivariable analysis found that the association between ACE2 transcription (log 2 fold-change) and the number of secondary transmission events differs between patients and healthcare workers. In health care workers Negative Binomial regression estimated that a one-unit change in ACE2 transcription decreases the number of secondary cases (β = -0.132 (95%CI: -0.255 to -0.0181) adjusting for RNA viral load. Conversely, in patients a one-unit change in ACE2 transcription increases the number of secondary cases (β = 0.187 (95% CI: 0.0101 to 0.370) adjusting for RNA viral load. Sensitivity analysis found no significant relationship between ACE2 and secondary transmission in health care workers and confirmed the positive association among patients. Conclusion Our study suggests that ACE2 transcription has a positive association with SARS-CoV-2 secondary transmission in admitted inpatients, but not health care workers in concurrent hospital associated outbreaks, and it should be further investigated as a risk-factor for viral transmission.

BackgroundThis study follows published associations in BC to 2014 (updated in 2019) to model the predicted incidence of asthma in BC children attributable to antibiotic use within the context of reduced antibiotic use and increased breastfeeding in BC infants from 2000 to 2019.MethodsA population-based ecological study was conducted in BC from 2000 to 2019, using outpatient antibiotic prescription data from BC PharmaNet and asthma diagnoses from the Chronic Disease Registry. Breastfeeding estimates were calculated using the Canadian Community Health Survey (CCHS). Population attributable risk (PAR) was calculated using a blended relative risk (RR) of asthma in antibiotic-exposed children who were and were not breastfed. PAR was used to calculate predicted vs. actual asthma incidence in 2019. Negative binomial regression was used to estimate the association between the average antibiotic prescription rate in infants under 1 and asthma incidence in 1–4 year olds, stratified by periods between 2000–2014 and 2015–2019.ResultsIn BC, antibiotic prescribing decreased by 77% in infants under 1 and asthma incidence decreased by 41% in children 1–4 years from 2000 to 2019. BC breastfeeding rates increased from 46% in the 2005 CCHS to 71% in the 2017/18 CCHS. After calculating the PAR using a blended RR, the predicted asthma incidence in 2019 was 18.8/1,000 population. This was comparable to the observed asthma incidence in children 1–4 years of 16.6/1,000 population in 2019. During 2000–2014, adjusted incidence risk ratio (aIRR) for children under Quintile 5 of average antibiotic prescribing was 1.75 (95% CI: 1.63–1.88, P < 0.0001) times higher than that for Quintile 1. However, between 2015 and 2019, this association weakened (as expected because of increasing prevalence of breastfeeding), with the expected asthma incidence for Quintile 5 only 11% (aIRR 1.11, 95% CI: 0.78–1.57) higher than for Quintile 1.ConclusionWe identified that over the past 20 years, antibiotic exposure in infants under 1 and asthma incidence in children 1–4 years has decreased significantly. Decreasing antibiotic exposure and increasing breastfeeding (which further mitigates risk associated with antibiotics) are of sufficient scale to explain much of this population trend. Changes in environmental, social and other exposures remain relevant to this complicated etiological pathway.

ObjectiveTo evaluate the impact of a personalised audit and feedback prescribing report (AF) and brief educational summary (ES) on empiric treatment of uncomplicated lower urinary tract infections (UTIs) by family physicians (FPs).DesignCluster randomised control trial.SettingThe intervention was conducted in British Columbia, Canada between 23 September 2021 and 28 March 2022.ParticipantsWe randomised 5073 FPs into a standard AF and ES intervention arm (n=1691), an ES-only arm (n=1691) and a control arm (n=1691).InterventionsThe AF contained personalised and peer-comparison data on first-line antibiotic prescriptions for women with uncomplicated lower UTI and key therapeutic recommendations. The ES contained detailed, evidence-based UTI management recommendations, incorporated regional antibiotic resistance data and recommended nitrofurantoin as a first-line treatment.Main outcome measuresNitrofurantoin as first-line pharmacological treatment for uncomplicated lower UTI, analysed using an intention-to-treat approach.ResultsWe identified 21 307 cases of uncomplicated lower UTI among the three trial arms during the study period. The impact of receiving both the AF and ES increased the relative probability of prescribing nitrofurantoin as first-line treatment for uncomplicated lower UTI by 28% (OR 1.28; 95% CI 1.07 to 1.52), relative to the delay arm. This translates to additional prescribing of nitrofurantoin as first-line treatment, instead of alternates, in an additional 8.7 cases of uncomplicated UTI per 100 FPs during the 6-month study period.ConclusionAF prescribing data with educational materials can improve primary care prescribing of antibiotics for uncomplicated lower UTI.Trial registration numberNCT05817253.