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Objective: We defined reference ranges for maternal cardiac output, systemic vascular resistance, and stroke volume measured in the third trimester of pregnancy using the Ultrasound Cardiac Output Monitor 1A. Design: Based on data from the prospective PEACH (PreEclampsia, Angiogenesis, Cardiac dysfunction and Hypertension) cohort study. Setting: Rigshospitalet and Hvidovre Hospital, Denmark. Sample: Normotensive pregnant women aged 18–45 years with singleton pregnancies, enrolled in the PEACH study in 2016–2018. Methods: We modelled cardiac output, systemic vascular resistance and stroke volume as a function of gestational age using multilevel linear models with fractional polynomials. Main Outcome Measures: Unconditional and conditional reference ranges for cardiovascular parameters measured in gestational weeks 28–40. Results: Our study cohort included 405 healthy pregnant women who contributed 1210 cardiovascular function measurements for analysis. Maximum cardiac output and stroke volume values were measured in gestational weeks 30–32 and decreased over the third trimester, whereas systemic vascular resistance increased during the same period. We created reference ranges for eight combinations of maternal height, age and parity. We also created a simple calculator to allow for implementation of the reference ranges in clinical practice. Conclusions: Our reference ranges allow the use of a bedside ultrasound device to non‐invasively assess cardiac function in pregnancy and identify women at risk of complications. The unconditional ranges allow clinicians to evaluate isolated measurements and identify women needing follow‐up. The conditional ranges incorporate information from previous measurements and improve monitoring over time. [ABSTRACT FROM AUTHOR]

Introduction: Preeclampsia and gestational diabetes mellitus share risk factors such as obesity and increased maternal age, which have become more prevalent in recent decades. We examined changes in the prevalence of preeclampsia and gestational diabetes between 2005 and 2018 in Denmark and Alberta, Canada, and investigated whether the observed trends can be explained by changes in maternal age, parity, multiple pregnancy, comorbidity, and body mass index (BMI) over time. Material and methods: This study was a register‐based cohort study conducted using data from the Danish National Health Registers and the provincial health registers of Alberta, Canada. We included in the study cohort all pregnancies in 2005–2018 resulting in live‐born infants and used binomial regression to estimate mean annual increases in the prevalence of preeclampsia and gestational diabetes in the two populations across the study period, adjusted for maternal characteristics. Results: The study cohorts included 846 127 (Denmark) and 706 728 (Alberta) pregnancies. The prevalence of preeclampsia increased over the study period in Denmark (2.5% to 2.9%) and Alberta (1.7% to 2.5%), with mean annual increases of 0.03 (95% confidence interval [CI] 0.02–0.04) and 0.06 (95% CI 0.05–0.07) percentage points, respectively. The prevalence of gestational diabetes also increased in Denmark (1.9% to 4.6%) and Alberta (3.9% to 9.2%), with average annual increases of 0.20 (95% CI 0.19–0.21) and 0.44 (95% CI 0.42–0.45) percentage points. Changes in the distributions of maternal age and BMI contributed to increases in the prevalence of both conditions but could not explain them entirely. Conclusions: The prevalence of both preeclampsia and gestational diabetes increased significantly from 2005 to 2018, which portends future increases in chronic disease rates among affected women. Increasing demand for long‐term follow up and care will amplify the existing pressure on healthcare systems. [ABSTRACT FROM AUTHOR]

Hyponatremia is a known adverse effect of thiazide antihypertensive medications, but its frequency is uncertain and believed to be very uncommon to rare. This population-based study emulates a target trial to characterize the incidence of hyponatremia after treatment initiation with thiazide medication compared with nonthiazide alternatives. Visual Abstract. Cumulative Incidence of Thiazide-Induced Hyponatremia: Hyponatremia is a known adverse effect of thiazide antihypertensive medications, but its frequency is uncertain and believed to be very uncommon to rare. This population-based study emulates a target trial to characterize the incidence of hyponatremia after treatment initiation with thiazide medication compared with nonthiazide alternatives. Background: According to drug labels, the frequency of thiazide-induced hyponatremia is unknown or uncommon to very rare (that is, <1 in 10 000 to <1 in 100), but the exact burden remains unclear. Objective: To estimate the increase in the cumulative incidence of hyponatremia using thiazide diuretics compared with nonthiazide antihypertensive drugs in routine clinical practice. Design: Population and register-based cohort study using target trial emulation. Setting: Denmark, 1 January 2014 to 31 October 2018. Participants: Two target trials were emulated among persons aged 40 years or older who had no recent prescription for any antihypertensive drug, had no previous hyponatremia, and were eligible for the studied antihypertensive treatments. The first target trial emulation compared new use of bendroflumethiazide (BFZ) versus a calcium-channel blocker (CCB). The second target trial emulation compared new use of hydrochlorothiazide plus a renin–angiotensin system inhibitor (HCTZ–RASi; that is, combination pill) versus a RASi alone. Measurements: Two-year cumulative incidences of sodium levels less than 130 mmol/L using stabilized inverse probability of treatment–weighted survival curves. Results: The study compared 37 786 new users of BFZ with 44 963 of a CCB and 11 943 new users of HCTZ–RASi with 85 784 of a RASi. The 2-year cumulative incidences of hyponatremia were 3.83% for BFZ and 3.51% for HCTZ–RASi. The risk differences were 1.35% (95% CI, 1.04% to 1.66%) between BFZ and CCB and 1.38% (CI, 1.01% to 1.75%) between HCTZ–RASi and RASi; risk differences were higher with older age and higher comorbidity burden. The respective hazard ratios were 3.56 (CI, 2.76 to 4.60) and 4.25 (CI, 3.23 to 5.59) during the first 30 days since treatment initiation and 1.26 (CI, 1.09 to 1.46) and 1.29 (CI, 1.05 to 1.58) after 1 year. Limitation: The study assumed that filled prescriptions equaled drug use, and residual confounding is likely. Conclusion: Treatment initiation with thiazide diuretics suggests a more substantial excess risk for hyponatremia, particularly during the first months of treatment, than indicated by drug labeling. Primary Funding Source: Independent Research Fund Denmark. [ABSTRACT FROM AUTHOR]

Background Data about the clinical benefit from initial low-density lipoprotein cholesterol (LDL-C) reduction with lipid lowering treatment for secondary prevention and risk of major vascular events amongst older as compared with younger individuals treated during routine clinical care are limited. We investigated this in a nationwide cohort. Methods Individuals aged ≥ 50 years with a first-time hospitalisation for a cardiovascular event (index event, including acute coronary syndrome, non-haemorrhagic stroke, transient ischaemic attack and coronary revascularisation), 1 January 2008 to 31 October 2018, who subsequently used lipid lowering treatment, and had an LDL-C measurement before and after the event were included. Hazard ratios (HRs) for major vascular events per 1 mmol/L reduction in LDL-C were estimated for the included 21,751 older and 22,681 younger individuals (≥/<70 years old) using Cox regression. Results LDL-C lowering was associated with a 12% lower risk of major vascular events in older individuals per 1 mmol/L reduction in LDL-C (HR 0.88, 95% confidence interval [CI] 0.84–0.93), with no significant difference compared with the risk reduction amongst younger individuals (HR 0.88, 95% CI 0.83–0.93; P -value for difference between age groups: 0.86). The risk reduction was more pronounced when post hoc restricting, as a proxy for compliance, to new users with an LDL-C reduction above the lowest decile for both older (0.81, 95% CI 0.73–0.90) and younger (0.81, 95% CI 0.72–0.91) individuals. Conclusions This study strongly supports a similar relative clinical benefit of LDL-C reduction with lipid lowering treatment for secondary prevention of major vascular events amongst individuals aged ≥70 and <70 years. [ABSTRACT FROM AUTHOR]

This document is a reply to correspondence regarding a study on the effectiveness of pollen allergen immunotherapy (AIT) in treating allergic rhinitis over 18 years in Denmark. The authors address comments made by Porsbjerg et al. and provide explanations and justifications for their methodology. They discuss the inclusion of patients with confirmed diagnoses of allergic rhinitis, the matching of treatment and non-treatment groups, the generalizability of the study, and the use of a binary outcome measure. The authors conclude that their study provides valuable insights into the effectiveness of pollen AIT in stopping allergic rhinitis symptoms. [Extracted from the article]