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Background: Because long‐term effectiveness of pollen allergen immune therapy (AIT) for allergic rhinitis (AR) is not well‐described, we studied effectiveness over 18 years in Denmark. Methods: A register‐based cohort study using data on filled prescriptions, 1995–2016, Denmark. In a cohort of 1.1 million intranasal corticosteroid inhaler users (proxy for AR), we matched users treated with grass, birch or mugwort AIT 1:2 with non‐treated users on baseline year and 24 characteristics in the 3 years prior to baseline. The primary outcome was the odds ratio (OR) of using anti‐allergic nasal inhaler during the pollen season in the treated versus non‐treated group by years since baseline. Results: Among 7760 AR patients treated with pollen AIT, the OR of using nasal inhaler 0–5 years after baseline was reduced when compared with 15,520 non‐treated AR individuals (0–2 years, OR 0.84 (0.81–0.88); 3–5 years, OR 0.88 (0.84–0.92)), but was close to unity or higher thereafter (6–9 years, OR 1.03 (0.97–1.08); 10–18 years, OR 1.18 (1.11–1.26)). In post hoc analyses, results were more consistent for those who already had 3 of 3 baseline years of use, and in patients using nasal inhaler in the latest pollen season (0–2 years, OR 0.76 (0.72–0.79); 3–5 years OR 0.86 (0.81–0.93); 6–9 years, OR 0.94 (0.87–1.02); 10–18 years, OR 0.94 (0.86–1.04)) as opposed to no such use. Conclusions: Patients treated with pollen AIT in routine care to a higher degree stopped using anti‐allergic nasal inhaler 0–5 years after starting the standard 3 years of therapy, and not beyond 5 years. Post hoc analyses suggested effectiveness was more consistent among patients with persistent AR. [ABSTRACT FROM AUTHOR]

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]

Migrants in Europe face a disproportionate burden of HIV infection; however, it remains unclear if this can be prevented through public health interventions in host countries. We undertake a systematic review and meta-analysis to estimate post-migration HIV acquisition (PMHA) as a proportion of all HIV cases in European migrants. MEDLINE, EMBASE, Global Health, HMIC, and Cochrane Library were searched with terms capturing 'HIV', 'migration', and 'Europe'. Data relating to the proportion of HIV acquired following migration were extracted and random-effects model (REM) meta-analysis was undertaken to calculate a pooled estimate for the proportion of PMHA in European countries. Subgroup meta-analysis was undertaken for PMHA by migrant demographic characteristics and host country. Fifteen articles were included for systematic review following retrieval and screening of 2,320 articles. A total of 47,182 migrants in 11 European countries were included in REM meta-analysis, showing an overall PMHA proportion of 0.30 (95% CI: 0.23–0.38). Subgroup analysis showed no significant difference in PMHA between host country and migrant demographic characteristics. This work illustrates that migrants continue to be at high risk of HIV acquisition in Europe. This indicates the need for targeted screening and HIV prevention interventions, ensuring resources are appropriately directed to combat the spread of HIV. [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]

Recommendations for statin use for primary or secondary prevention are based on studies that underrepresent persons older than 75 years. This Danish, national, register-based cohort study compares the low-density lipoprotein cholesterol response to different-intensity statin use in older versus younger persons. Visual Abstract. The Association Between Age and Low-Density Lipoprotein Cholesterol Response to Statins: Recommendations for statin use for primary or secondary prevention are based on studies that underrepresent persons older than 75 years. This Danish, national, register-based cohort study compares the low-density lipoprotein cholesterol response to different-intensity statin use in older versus younger persons. Background: There is large patient-to-patient variability in the low-density lipoprotein cholesterol (LDL-C) response to statin treatment. The reduction in LDL-C may depend on the age of the patient treated—particularly in older adults, who have been substantially underrepresented in randomized controlled trials. Objective: To investigate the association between age and the LDL-C reduction by statins. Design: Nationwide, register-based cohort study. Setting: Denmark, 2008 to 2018. Participants: 82 958 simvastatin or atorvastatin initiators with LDL-C measurements before and during statin use. Measurements: Statin response, defined as percentage reduction in prestatin LDL-C level, and percentage reduction differences (PRDs) according to age and simvastatin or atorvastatin dose based on a longitudinal model for LDL-C. Results: Among 82 958 statin initiators, 10 388 (13%) were aged 75 years or older. With low- to moderate-intensity statins, initiators aged 75 years or older had greater mean LDL-C percentage reductions than initiators younger than 50 years—for example, 39.0% versus 33.8% for simvastatin, 20 mg, and 44.2% versus 40.2% for atorvastatin, 20 mg. The adjusted PRD for initiators aged 75 years compared with initiators aged 50 years was 2.62 percentage points. This association was consistent for primary prevention (2.54 percentage points) and secondary prevention (2.32 percentage points) but smaller for initiators of high-intensity statins (atorvastatin, 40 mg: 1.36 percentage points; atorvastatin, 80 mg: −0.58 percentage point). Limitation: Use of administrative data, observational pre–post comparison with a moderately high proportion of missing data, lack of information on body mass index, and the mainly White study population may limit generalizability. Conclusion: Low- to moderate-intensity statins were associated with a greater reduction in LDL-C levels in older persons than younger persons and may be more appealing as initial treatment in older adults who are at increased risk for adverse events. Primary Funding Source: The Independent Research Fund Denmark, Brødrene Hartmanns Fond, and Fonden til Lægevidenskabens Fremme. [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]

OBJECTIVE: It has been hypothesized that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in children can increase risk of developing type 1 diabetes. RESEARCH DESIGN AND METHODS: We undertook a prospective, register-based analysis of children in Denmark by investigating the association between SARS-CoV-2 infection and subsequent risk of type 1 diabetes. During the pandemic, Denmark had one of the highest test rates per capita in the world, and 90% of all Danish children were tested. RESULTS: Compared with children with a history of only negative SARS-CoV-2 tests, we did not observe a higher risk of first-time diagnosis of type 1 diabetes in children 30 days or more after a positive SARS-CoV-2 test (hazard ratio 0.85; 95% CI 0.70–1.04). CONCLUSIONS: Our data do not support that SARS-CoV-2 infection is associated with type 1 diabetes or that type 1 diabetes should be a special focus after a SARS-CoV-2 infection in children. [ABSTRACT FROM AUTHOR]

Background: Previous research has suggested that some women are at increased risk of postpartum depression (PPD) because of an extra sensitivity to fluctuating hormones before and after parturition. This may particularly apply to women with endocrine disease, characterised by a less than optimal capability to self-regulate the hormonal feedback system. Aims: To investigate if women with endocrine disease history are at increased risk of developing PPD. Method: Based on information from Danish national registers, this nationwide cohort study included 888 989 deliveries (1995–2018). Endocrine disease history was defined as thyroid disease, pre-pregnancy diabetes, polycystic ovary syndrome and/or previous gestational diabetes within 10 years before pregnancy start. PPD was defined as use of antidepressants and/or hospital contact for depression within 6 months after childbirth. Results: Among 888 989 deliveries, 4.1% had a history of endocrine disease and 0.5% had a PPD episode. Overall, women with an endocrine disease history had a 42% (risk ratio 1.42, 95% CI 1.24–1.62) higher risk of PPD when compared with women with no endocrine disease. However, we also found the reverse association, whereby women with a PPD history had a 50% (hazard ratio 1.5, 95% CI 1.4–1.6) higher risk of endocrine disease when compared with women with no PPD history. Conclusions: Women with endocrine disease history had a 40% higher risk of PPD compared with women with no endocrine disease. More attention should be given to pregnant women with endocrine disease history to increase awareness of early signs of PPD. The bi-directionality of the association points to a common underlying factor. [ABSTRACT FROM AUTHOR]

Background: Individuals with a prior Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection have a moderate to high degree of protection against reinfection, though seemingly less so when the Omicron variant of SARS-CoV-2 started to circulate. The aim of this study was to evaluate the vaccine effectiveness (VE) against SARS-CoV-2 reinfection, Coronavirus Disease 2019 (COVID-19)-related hospitalization, and COVID-19-related death, in individuals with prior SARS-CoV-2 infection, and to assess the effect of time since vaccination during periods with different dominant SARS-CoV-2 variants.Methods and Findings: This study used a nationwide cohort design including all individuals with a confirmed SARS-CoV-2 infection, who were alive, and residing in Denmark between 1 January 2020 and 31 January 2022. Using Danish nationwide registries, we obtained information on SARS-CoV-2 infections, COVID-19 vaccination, age, sex, comorbidity, staying at hospital, and country of origin. The study population included were individuals with prior SARS-CoV-2 infection. Estimates of VE against SARS-CoV-2 reinfection with 95% confidence intervals (CIs) were calculated using a Poisson regression model and adjusted for age, sex, country of origin, comorbidity, staying at hospital, calendar time, and test incidence using a Cox regression model. The VE estimates were calculated separately for three periods with different dominant SARS-CoV-2 variants (Alpha (B.1.1.7), Delta (B.1.617.2), or Omicron (B.1.1.529)) and by time since vaccination using unvaccinated as the reference. In total, 148,527 person-years and 44,192 SARS-CoV-2 infections were included for the analysis regarding reinfections. The study population comprised of 209,814 individuals infected before or during the Alpha period, 292,978 before or during the Delta period, and 245,530 before or during the Omicron period. Of these, 40,281 individuals had completed their primary vaccination series during the Alpha period (19.2%), 190,026 during the Delta period (64.9%), and 158,563 during the Omicron period (64.6%). VE against reinfection following any COVID-19 vaccine type administered in Denmark, peaked at 71% (95% CI: -Inf to 100%) at 104 days or more after vaccination during the Alpha period, 94% (95% CI: 92% to 96%) 14 to 43 days after vaccination during the Delta period, and 60% (95% CI: 58% to 62%) 14 to 43 days after vaccination during the Omicron period. Waning immunity following vaccination was observed and was most pronounced during the Omicron period. Due to too few events, it was not possible to estimate VE for hospitalization and death. Study limitations include potentially undetected reinfections, differences in health-seeking behavior, or risk behavior between the compared groups.Conclusions: This study shows that in previously infected individuals, completing a primary vaccination series was associated with a significant protection against SARS-CoV-2 reinfection compared with no vaccination. Even though vaccination seems to protect to a lesser degree against reinfection with the Omicron variant, these findings are of public health relevance as they show that previously infected individuals still benefit from COVID-19 vaccination in all three variant periods. [ABSTRACT FROM AUTHOR]

A woman's reproductive history is strongly associated with her risk of ovarian cancer. However, it is unclear how pregnancies of different duration impact a woman's ovarian cancer risk, and therefore, what part of a pregnancy explains the protective effect. Using a cohort of all Danish women followed from 1968 to 2018, with prospectively registered information on reproductive history (eg, gestational duration of pregnancies, tubal ligation and resection and hormonal pharmaceutical use), we investigated the effect of pregnancy duration on ovarian cancer risk. We adjusted for potential confounders, such as age at pregnancy and time since pregnancy, using log‐linear Poisson regression to isolate the effect of pregnancy duration on ovarian cancer risk. Among 2.5 million Danish women with 4.4 million pregnancies, a pregnancy was associated with a reduction of ovarian cancer risk of 21% (95% CI, 14%‐28%), 26% (95% CI, 21%‐31%), 12% (95% CI, 7%‐17%) and 3% (95% CI, −5% to 11%) compared to one less, for the first, second, third and fourth pregnancy, respectively (P <.001 for heterogeneity), with similar effects of induced abortions, spontaneous abortions and childbirths. Sensitivity analysis of age at pregnancy, time since pregnancy and other potential confounders did not change these findings. The reduced ovarian cancer risk associated with pregnancy is primarily driven by the first three pregnancies, with similar effects of induced abortion, spontaneous abortions and childbirth, suggesting that mainly exposure to early pregnancy factors, and not pregnancy duration, protect against ovarian cancer. [ABSTRACT FROM AUTHOR]