Long-term effects of allergen sensitization and exposure in adult asthma: a prospective study.

BACKGROUND: : We investigated the effects of sensitization and exposure to common domestic allergens on longitudinal changes in lung function and bronchial hyperresponsiveness. METHODS: : Subjects attended 2 visits that were 4 years apart. Skin prick testing was performed and household dust samples were collected for quantification of mite, dog, and cat allergens at baseline. Measurements of lung function, exhaled nitric oxide, and bronchial hyperresponsiveness were completed at both visits. RESULTS: : Dust samples were collected in 165 of the 200 subjects completing both visits. Mean length of follow-up was 47 months. Bronchial hyperresponsiveness, measured at both visits in 86 subjects, deteriorated in those exposed to high mite allergen levels compared with those not exposed [mean (95% CI) doubling dose change PD20 = -0.44 (-1.07 to 0.19) vs 0.82 (0.27 to 1.36)], but improved in those exposed to high dog allergen levels compared with those not exposed [1.10 (0.33 to 1.86) vs 0.10 (-0.39 to 0.58)]. The associations were significant in the multivariate models. Cat allergen exposure was not associated with any changes in lung function, exhaled nitric oxide, or bronchial hyperresponsiveness. CONCLUSIONS: : In a 4-year prospective cohort of persons with asthma, exposure to high levels of dust mite allergens at baseline was associated with a subsequent increase in bronchial hyperresponsiveness

On the Amplitude of Convective Velocities in the Deep Solar Interior

We obtain lower limits on the amplitude of convective velocities in the deep solar convection zone based only on the observed properties of the differential rotation and meridional circulation together with simple and robust dynamical balances obtained from the fundamental MHD equations. The linchpin of the approach is the concept of gyroscopic pumping whereby the meridional circulation across isosurfaces of specific angular momentum is linked to the angular momentum transport by the convective Reynolds stress. We find that the amplitude of the convective velocity must be at least 30 m s$^{-1}$ in the upper CZ ($r \sim 0.95 R$) and at least 8 m s$^{-1}$ in the lower CZ ($r \sim 0.75 R$) in order to be consistent with the observed mean flows. Using the base of the near-surface shear layer as a probe of the rotational influence, we are further able to show that the characteristic length scale of deep convective motions must be no smaller than 5.5--30 Mm. These results are compatible with convection models but suggest that the efficiency of the turbulent transport assumed in advection-dominated flux-transport dynamo models is generally not consistent with the mean flows they employ.Comment: 16 pages, 4 figures, accepted to the Astrophysical Journa

Temporal trends in the initiation of dialysis among patients with heart failure with or without diabetes: a nationwide study from 2002 to 2016

Background The incidence and distribution of acute and chronic dialysis among patients with heart failure (HF), stratified by diabetes, remain uncertain. We hypothesized that with improved survival and rising comorbidities, the demand for dialysis would increase over time. Methods and Results Patients with incident HF, aged 18 to 100 years, between 2002 and 2016, were identified using Danish nationwide registers. Primary outcomes included acute and chronic dialysis initiation, HF‐related hospitalization, and all‐cause mortality. These outcomes were assessed in 2002 to 2006, 2007 to 2011, and 2012 to 2016, stratified by diabetes. We calculated incidence rates (IRs) per 1000 person‐years and hazard ratios (HR) using multivariable Cox regression. Of 115 533 patients with HF, 2734 patients received acute dialysis and 1193 patients received chronic dialysis. The IR was 8.0 per 1000 and 3.5 per 1000 person‐years for acute and chronic dialysis, respectively. Acute dialysis rates increased significantly among patients with diabetes over time, while no significant changes occurred in those without diabetes, chronic dialysis, HF‐related hospitalization, or overall mortality. Diabetes was associated with significantly higher HRs of acute and chronic dialysis, respectively, compared with patients without diabetes (HR, 2.07 [95% CI, 1.80–2.39] and 2.93 [95% CI, 2.40–3.58] in 2002 to 2006; HR, 2.45 [95% CI, 2.14–2.80] and 2.86 [95% CI, 2.32–3.52] in 2007 to 2011; and 2.69 [95% CI, 2.33–3.10] and 3.30 [95% CI, 2.69–4.06] in 2012 to 2016). Conclusions The IR of acute and chronic dialysis remained low compared with HF‐related hospitalizations and mortality. Acute dialysis rates increased significantly over time, contrasting no significant trends in other outcomes. Diabetes exhibited over 2‐fold increased rates of the outcomes. These findings emphasize the importance of continued monitoring and renal care in patients with HF, especially with diabetes, to optimize outcomes and prevent adverse events

CHA2DS2-VASc score and risk of thromboembolism and bleeding in patients with atrial fibrillation and recent cancer

Background Cancer may influence the risk of thromboembolism and bleeding associated with the CHA2DS2-VASc score. We examined the risk of thromboembolism and bleeding associated with the CHA2DS2-VASc score in atrial fibrillation patients with and without recent cancer. Methods and results Using nationwide registers all patients diagnosed with atrial fibrillation from 2000 to 2015 and not on oral anticoagulation or heparin therapy were included and followed for 2 years. Recent cancer was defined by a cancer diagnosis 5 years or fewer earlier. Risks of thromboembolism and bleeding were estimated in cumulative incidence curves and Cox regression models. We included 122,053 patients with incident atrial fibrillation, 12,014 (10%) had recent cancer. The 2-year cumulative incidence of thromboembolism and bleeding in patients with versus without recent cancer was 1.7% (95% confidence interval (CI) 0.5–2.8) and 4.3% (95% CI 2.4–6.2) versus 1.2% (95% CI 0.9–1.5) and 1.7% (95% CI 1.4–2.0) for CHA2DS2-VASc score 0; 3.2% (95%CI 2.2-4.3) and 4.4% (95%CI 3.2-5.6) versus 1.8% (95%CI 1.6-2.1) and 3.0% (95% CI 2.7–3.3) for CHA2DS2-VASc score 1; and 7.1% (95% CI 6.6–7.7) and 6.8% (95% CI 6.3–7.2) versus 10.9% (95% CI 10.7–11.1) and 6.2% (95% CI 6.1–6.4) for CHA2DS2-VASc score 2 or greater. Although the CHA2DS2-VASc score was associated with thromboembolism and bleeding in both patients with and without cancer, the association differed between the groups for thromboembolism (test for interaction, p &lt; 0.001) and bleeding (test for interaction, p &lt; 0.001). Conclusion The association of the CHA2DS2-VASc score and risk of thromboembolism and bleeding differed between atrial fibrillation patients with and without recent cancer. Therefore, the CHA2DS2-VASc score should be used with caution in patients with recent cancer. </jats:sec

Protocol for a randomised controlled trial comparing warfarin with no oral anticoagulation in patients with atrial fibrillation on chronic dialysis: the Danish Warfarin-Dialysis (DANWARD) trial

INTRODUCTION: Atrial fibrillation is highly prevalent in patients on chronic dialysis. It is unclear whether anticoagulant therapy for stroke prevention is beneficial in these patients. Vitamin K-antagonists (VKA) remain the predominant anticoagulant choice. Importantly, anticoagulation remains inconsistently used and a possible benefit remains untested in randomised clinical trials comparing oral anticoagulation with no treatment in patients on chronic dialysis. The Danish Warfarin-Dialysis (DANWARD) trial aims to investigate the safety and efficacy of VKAs in patients with atrial fibrillation on chronic dialysis. The hypothesis is that VKA treatment compared with no treatment is associated with stroke risk reduction and overall benefit.METHODS AND ANALYSIS: The DANWARD trial is an investigator-initiated trial at 13 Danish dialysis centres. In an open-label randomised clinical trial study design, a total of 718 patients with atrial fibrillation on chronic dialysis will be randomised in a 1:1 ratio to receive either standard dose VKA targeting an international normalised ratio of 2.0-3.0 or no oral anticoagulation. Principal analyses will compare the risk of a primary efficacy endpoint, stroke or transient ischaemic attack and a primary safety endpoint, major bleeding, in patients allocated to VKA treatment and no treatment, respectively. The first patient was randomised in October 2019. Patients will be followed until 1 year after the inclusion of the last patient.ETHICS AND DISSEMINATION: The study protocol was approved by the Regional Research Ethics Committee (journal number H-18050839) and the Danish Medicines Agency (case number 2018101877). The trial is conducted in accordance with the Helsinki declaration and standards of Good Clinical Practice. Study results will be disseminated to participating sites, at research conferences and in peer-reviewed journals.TRIAL REGISTRATION NUMBERS: NCT03862859, EUDRA-CT 2018-000484-86 and CTIS ID 2022-502500-75-00.</p