Health Canada advisory impacts on the prevalence of oral codeine use in the Pediatric Canadian population: comparative study across provinces.

Health Canada (HC) has, since 2013, issued safety alerts restricting the use of codeine-containing drugs among breastfeeding women and children/adolescents under 18 years of age. These products are linked to breathing problems among ultra-rapid CYP2D6 metabolizers and early use of opioid can lead to future opioid misuse. Using a multi-province population-based cohort study, we estimate the impact of federal safety alerts on annual rates of codeine use in the Canadian pediatric population. We analyzed data from 8,156,948 children/adolescents in five Canadian provinces between 1996 and 2021, using a common protocol. Children/adolescents were categorized as: ≤ 12 years (children) or > 12 years (adolescents). We defined codeine exposure by ≥ 1 prescription filled for codeine alone or combined with other medications. For both age categories, we obtained province-specific codeine prescription filling rates per calendar year by dividing the number of children/adolescents with ≥ 1 codeine prescription filled by the number of person-time. Annual rates of codeine use per 1000 persons vary by province from 3.0 (Quebec) to 10.1 (Manitoba) in children, and from 5.5 to 51.3 in adolescents. After the 2013 HC advisory, exposure decreased in all provinces (adjusted level change from - 0.6 to - 18.4%) in children and from - 2.1 to - 17.9% in adolescents after the 2016 advisory. Annual rates declined over time in all provinces, following HC safety alerts specific to each of the two age categories.

Arterial stiffness for the early prediction of pre-eclampsia compared with blood pressure, uterine artery Doppler and angiogenic biomarkers: a prospective cohort study.

OBJECTIVE: Our aim was to evaluate the ability of arterial stiffness parameters to predict pre-eclampsia early compared with peripheral blood pressure, uterine artery Doppler and established angiogenic biomarkers. DESIGN: Prospective cohort study. SETTING: Tertiary care antenatal clinics in Montreal, Canada. POPULATION: Women with singleton high-risk pregnancies. METHODS: In the first trimester, arterial stiffness was measured by applanation tonometry, along with peripheral blood pressure and serum/plasma angiogenic biomarkers; uterine artery Doppler was measured in the second trimester. The predictive ability of different metrics was assessed through multivariate logistic regression. MAIN OUTCOME MEASURES: Arterial stiffness (carotid-femoral pulse wave velocity, carotid-radial pulse wave velocity) and wave reflection (augmentation index, reflected wave start time), peripheral blood pressure, ultrasound indices of velocimetry and circulating angiogenic biomarker concentrations. RESULTS: In this prospective study, among 191 high-risk pregnant women, 14 (7.3%) developed pre-eclampsia. A first-trimester 1 m/s increase in carotid-femoral pulse wave velocity was associated with 64% increased odds (P < 0.05), and a 1-millisecond increase in time to wave reflection with 11% decreased odds for pre-eclampsia (P < 0.01). The area under the curve of arterial stiffness, blood pressure, ultrasound indices and angiogenic biomarkers was 0.83 (95% confidence interval [CI] 0.74-0.92), 0.71 (95% CI 0.57-0.86), 0.58 (95% CI 0.39-0.77), and 0.64 (95% CI 0.44-0.83), respectively. With a 5% false-positive rate, blood pressure had a sensitivity of 14% for pre-eclampsia and arterial stiffness a sensitivity of 36%. CONCLUSIONS: Arterial stiffness predicted pre-eclampsia earlier and with greater ability than blood pressure, ultrasound indices or angiogenic biomarkers.

Carotid endarterectomy improves peripheral but not central arterial stiffness.

OBJECTIVE: Carotid endarterectomy (CEA) reduces the risk of cerebrovascular events due to the presence of atherosclerotic plaque in the internal carotid artery. Arterial stiffness is an indicator of cardiovascular risk and strongly associates with the development of atherosclerosis. This study aims to assess the short-term effect of CEA on arterial stiffness and haemodynamics. DESIGN: Prospective observational study. METHODS: Measurements of arterial stiffness and haemodynamics, including carotid-femoral pulse wave velocity (cfPWV), carotid-radial PWV (crPWV), augmentation pressure, augmentation index, subendocardial viability ratio, central pressures and pulse pressure amplification, were performed pre- and 6 weeks post-CEA on both surgical and non-surgical sides. RESULTS: Fifty-nine patients completed the study (n = 46 men, age 68.9 ± 10.1 years). crPWV was decreased after CEA on the surgical (P = 0.01) and non-surgical side (P = 0.0008), AIx75 tended to decrease only on the surgical side (P = 0.06). cfPWV did not change significantly on either side. CONCLUSION: We assessed, for the first time, the short-term effect of CEA on arterial stiffness and haemodynamics. CEA improved peripheral but not central arterial stiffness. This study provides evidence for significant changes in certain arterial stiffness and haemodynamic parameters. Longer-term follow-up will assess whether these changes are sustained and whether CEA is associated with further haemodynamic benefits.