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Daily hassles and cortisol suppression following low-dose dexamethasone suppression test are independently associated with cardiovascular disease
No full textObjective: Chronic stress is linked to cardiometabolic diseases through increased glucocorticoid exposure, but the impact of daily life stress on glucocorticoid regulation and cardiometabolic health remains underexplored. This study investigated these associations. Design This is a cross-sectional analysis of participants from the Netherlands Study of Depression and Anxiety (NESDA) without psychiatric diagnosis in the prior 6 months. Methods: We included 870 participants (64.7% female, median age 47.0 years). Daily life stress was assessed using the Daily Hassles Questionnaire (DHQ). Salivary cortisol was analyzed for 1-h awakening cortisol (4 time points), evening cortisol, and slope. Also an overnight 0.5 mg dexamethasone suppression test was performed. Associations between DHQ, glucocorticoid measures, and cardiometabolic health were studied using logistic and linear regressions. Results: After multivariable adjustment, each standard deviation (SD) increase in DHQ score was associated with 1.38 times (95% confidence interval [CI] 1.07; 1.77) higher odds of cardiovascular disease (CVD), but not diabetes, metabolic syndrome, or obesity. Higher DHQ scores were also associated with higher evening cortisol levels. In addition, each SD increase in cortisol suppression ratio was associated with 1.36 times (95% CI 1.08; 1.72) higher odds of CVD, but not diabetes, metabolic syndrome, or obesity. No interactions between DHQ and glucocorticoid measures on CVD were observed. Conclusion: A higher cortisol suppression ratio, indicative of increased glucocorticoid sensitivity, and increased daily hassles were both independently associated with having CVD. The absence of interaction suggests they influence CVD through separate pathways, highlighting the need for further research to better understand stress mechanisms and identify “stress profiles” most closely linked to cardiometabolic diseases.</p
Reply:From the authors of the ERS/ATS statement on the international multidisciplinary classification of the interstitial pneumonias
No full textAnticoagulation Therapeutic Ranges and Clinical Outcomes in Patients with a Mechanical Heart Valve Treated with Vitamin K Antagonists:a Nationwide Linked-data Dutch Study
No full textAims:To examine the impact of different therapeutic international normalized ratio (INR) ranges on anticoagulation control and clinical outcomes in patients with mechanical heart valves (MHVs) treated with vitamin K antagonists (VKAs) in the Netherlands. Methods:Data from 17 anticoagulation clinics (2013–2019) were linked to nation-wide data from Statistics Netherlands. Anticoagulation control metrics included significant dose adjustments, INR variance growth rate, and time in therapeutic range. Cause-specific Cox regression models were used to assess associations between therapeutic ranges and clinical outcomes, accounting for death as competing risk. Stratified analyses were performed for significant interactions by type of MHV recipient. Results:Among 3,473 MHV patients (median age: 67.0 [IQR: 58.0-76.0], 61.7% male, 68.2% acenocoumarol, 26.5% phenprocoumon), patients with lower therapeutic ranges (N ¼ 1,866) (2.0–3.0 for isolated aortic valve without risk factors; 2.5–3.5 for all remaining MHV patients) had poorer anticoagulation control compared to those with higher ranges (N ¼ 1,607) (2.5–3.5 and 3.0–4.0, respectively). No association was found between therapeutic ranges and major/clinically relevant bleeding (fully adjusted hazard ratio [aHR]: 0.80 [95%CI: 0.57–1.1]). However, in patients with a non-aortic valve and/or additional risk factors a lower therapeutic range was potentially associated with increased thromboembolic risk (aHR: 1.3 [95% CI: 0.94–1.9]), while no association was observed in patients with an isolated aortic valve (aHR: 0.71 [95%CI: 0.38–1.3]). Conclusion:A lower therapeutic range does not apparently increase thromboembolic risk in most MHV patients but may be associated with a higher thromboembolic risk in higher risk patients. Lower therapeutic ranges were not associated with lower bleeding risk.<p/
Sex-based differences in biomarker trajectories in acute coronary syndrome patients from the BIOMArCS study
No full textAcute coronary syndrome (ACS) presents sex-based differences in pathophysiology. Variations in biomarker patterns post-ACS, reflecting myocardial injury, vascular inflammation, and remodeling, may indicate critical differences in cardiovascular disease mechanisms and outcomes. We analyzed biomarker patterns in 787 patients (22% females) from the BIOMArCS study, all without re-ACS during the study period. We tracked levels of hs-cTnT, NT-proBNP, hs-CRP, GDF-15, and additional biomarkers in a subcohort of 191 patients over one year. Serial blood samples were collected to compare acute-phase (first month after ACS) and stabilized-phase (2–12 months post-ACS) biomarker trajectories between sexes, adjusting for age, BMI, and kidney function using linear mixed-effects models. Females showed significantly lower hs-cTnT levels (mean 386 pg/mL versus 559 pg/mL in males, p = 0.002 acute phase; 8.5 pg/mL versus 10.8 pg/mL, p < 0.001 at 180 days). NT-proBNP levels were higher in females (mean 70 pmol/L vs. 47 pmol/L, p < 0.001 acute phase; 30 pmol/L vs. 19 pmol/L, p < 0.001 at 180 days). Hs-CRP levels were also elevated in females (mean 1.8 mg/L vs. 1.5 mg/L, p = 0.02 at 180 days). Galectin-3 levels remained higher in females (22.8 ng/mL vs. 18.6 ng/mL, p = 0.03). This study provides the first comprehensive analysis of sex-specific biomarker trajectories following ACS. Distinct differences in hs-cTnT, NT-proBNP, and inflammatory markers suggest that sex-specific diagnostic thresholds and personalized treatment strategies after ACS may be warranted, although their clinical value still needs confirmation in larger prospective studies.</p
Two-year persistence of MERS-CoV-specific antibody and T cell responses after MVA-MERS-S vaccination in healthy adults
No full textMVA-MERS-S, a vaccine candidate against Middle East respiratory syndrome (MERS), was recently evaluated in a randomized, placebo-controlled, double-blind phase 1b clinical trial to assess its safety, immunogenicity, and optimal dosing in healthy adults in Hamburg and Rotterdam. A three-dose regimen was safe and elicited robust spike-specific antibody responses. We extended this trial to assess the two-year durability of MERS-CoV-specific antibody and T cell responses in 48 study participants of the Hamburg cohort. Our findings show that immune responses remain detectable for at least 24 months after the third vaccination. Antibodies persisted at levels comparable to the peak response observed after the second vaccination and were able to cross-neutralize MERS-CoV spike mutants. Although the immune correlates of protection against MERS remain unknown, the observed durability of humoral and cellular immune responses supports the potential of MVA-MERS-S as a promising MERS vaccine candidate and highlights the importance of a booster dose in sustaining long-term immunity.</p
Diagnostic Delay in Patients With Chronic Urticaria:Results From the Chronic Urticaria Registry (CURE)
No full textBackground: Chronic urticaria (CU) diagnosis includes the patient's clinical history and physical examination. However, atypical presentations or misdiagnosis can lead to diagnostic delay (DD). Objective: The impact and contributing factors of DD in CU are unknown and were assessed in the present study. Methods: We retrospectively analysed data from CU adult patients from the international, multicenter Chronic Urticaria Registry (CURE). Results: Of 4332 CU patients, 61% had standalone chronic spontaneous urticaria (sCSU), 18% had ≥ 1 form of chronic inducible urticaria (CIndU), and 21% had a combination of both (CSU + CIndU). Diagnosis of CU was delayed in 24% of patients by at least 1 year. CIndU patients showed a longer DD compared to those with sCSU or CSU + CIndU (median, [IQR]: 4, [0–22] vs. 1, [0–6] vs. 2, [0–9] months, p < 0.001). Among CIndU patients, symptomatic dermographism (n = 264) and cholinergic urticaria (n = 103) patients had the longest DD compared to all other CIndU subgroups (median: 4 months, p = 0.005 for both). In CIndU patients, a longer DD was associated with having an additional CIndU (OR: 12.8, p = 0.03), younger age, comorbidities, lower disease control, and lack of second-generation H1-antihistamine treatment. In CSU patients, a DD of ≥ 6 months was associated with lower CSU activity (median weekly Urticaria Activity Score of 14 vs. 21, p = 0.02) compared to that of DD < 6 months.Conclusions: Diagnosis of CU is delayed in one out of four patients. Greater awareness of the guideline-recommended CU classification, clinical presentation, and diagnostic work-up can facilitate CU diagnosis.</p
Incidence and management of first metatarsophalangeal joint osteoarthritis in Dutch general practice estimates from the Rijnmond Primary Care Database
No full textOBJECTIVE: Osteoarthritis (OA) of the first metatarsophalangeal (MTP) joint is accompanied by pain and stiffness and associated with reduced health-related quality of life. Although prevalence of radiographic 1st MTP joint OA is high, the incidence of clinical 1st MTP joint OA is unknown. Therefore, we aimed to determine the incidence and management of general practice (GP) consultations for symptomatic 1st MTP joint OA. METHODS: A retrospective cohort study was conducted using electronic health records of GPs. An algorithm was defined to identify 1st MTP joint OA patients based on free text and codified data between 2013 and 2022. First MTP joint OA incidence rate, comorbidities and management strategies were assessed. RESULTS: The overall 1st MTP joint OA incidence was 0.74/1000 person-years in patients ≥35 years. The most initiated management by GPs was explanation/reassurance (360/672 (53.6 %)), followed by referral to podiatry (171/672 (25.4 %)) and orthopedic surgeon consultation (162/672 (24.1 %)). Of the 823 patients consulting their GP with foot/toe problems in the year before diagnosis, 491 (47.1 %) were referred to radiology, and 271 (26 %) for orthopedic surgeon consultation. CONCLUSION: The incidence of 1st MTP joint OA has been estimated for the first time in general practice. Most patients are diagnosed after referral to radiology or orthopedic surgeon consultation. From diagnosis, half of 1st MTP joint OA patients are referred, mostly for orthopedic surgeon consultation and podiatry. As evidence for these diagnostic and management strategies is lacking, research into their effectiveness for 1st MTP joint OA in general practice is needed.</p
Changes in sleep precede cognitive decline across two population cohorts:Unlocking the potential of sleep as an early marker of dementia
No full textUltrashort echo time MRI radiomics as a predictor of clinical outcomes in patellar tendinopathy:Insights from a large prospective clinical trial
No full textPurpose:To evaluate the predictive utility of radiomic features extracted from ultrashort echo time (UTE) MRI in comparison to conventional proton density (PD) sequences for short-term (24-week) and long-term (5-year) clinical outcomes in patients with patellar tendinopathy (PT) receiving exercise therapy. Materials and methods:This prospective study of 76 PT patients undergoing 24-week exercise therapy underwent baseline 3D UTE and PD MRI at 3.0 T. The patellar tendon segmentation used nnU-Net, evaluated with Dice coefficient. Six predictive models consisting of clinical covariates and radiomic features from UTE and PD were developed using Elastic Net with 10-fold cross-validation. Model performance in predicting responsiveness of the patient-reported Victorian Institute of Sports Assessment (VISA-P) score was evaluated using the area under the receiver operating characteristic curve (ROC AUC) and the precision-recall curve (PR AUC), with 95% confidence intervals.Results:The mean Dice similarity coefficient for the automatic segmentation of the patellar tendon from 3D-PD was 0.92 (SD: 0.02) and from 3D-UTE-Cones 0.89 (SD: 0.03). The UTE-based radiomics model demonstrated the highest predictive performance at 24 weeks (ROC AUC: 0.714 [95% CI: 0.701–0.727]; PR AUC: 0.848 [0.837–0.858]), while the PD-based model showed the lowest (ROC AUC: 0.569 [0.553–0.584]; PR AUC: 0.710 [0.692–0.727]). At the 5-year follow-up, UTE radiomics maintained robust performance (ROC AUC: 0.692 [0.677–0.706]; PR AUC: 0.822 [0.810–0.834]), whereas PD radiomics remained limited (ROC AUC: 0.578 [0.561–0.594]; PR AUC: 0.694 [0.676–0.713]).Conclusions:Radiomics features extracted from UTE MRI demonstrate the highest predictive performance for clinical outcomes.</p
Impact of Dupilumab for Severe Asthma on Fatigue, Quality of Life, Work Productivity, and Activity
No full textBackground: Severe asthma greatly impacts daily life. Although biologics such as dupilumab improve clinical outcomes, their effects on patient-reported outcome measures prioritized by patients remain largely unexplored. Objective: (1) To evaluate changes in fatigue, quality of life (QoL), and work and activity impairment over 12 months following dupilumab initiation in a large severe asthma cohort. (2) To explore differences between biologic-naive patients and switchers and assess the relationship with asthma symptom control. Methods: Dutch severe asthma registry data were used, measuring fatigue (Checklist for Individual Strength – Subjective Fatigue), QoL (Asthma Quality of Life Questionnaire), work and activity impairment (Work Productivity and Activity Impairment – General Health), and asthma symptom control (6-item Asthma Control Questionnaire) at baseline and at 3, 6, 9, and 12 months. Changes over time and mean improvement “on dupilumab” (baseline vs 3-12 months) were explored using linear mixed models. Results: Among 236 patients (45% biologic-naive), median (interquartile range) baseline scores were 38 (29 to 47) for fatigue, 5.1 (4.4 to 5.9) for QoL, 35% (10 to 70) for work impairment, and 50% (20 to 70) for activity impairment. Mean improvement “on dupilumab” was −3.3 (95% CI, −4.7 to −1.9) for fatigue, 0.4 (0.3 to 0.5) for QoL, −9% (−15 to −2) for work impairment, and −6% (−10 to −3) for activity impairment. Improvements were greater in patients with larger asthma symptom control improvement. Minimal clinically important differences were achieved by 50% for the 6-item Asthma Control Questionnaire, 46% for QoL, and 30% or less for fatigue and work and activity impairment, with higher rates among those impaired at baseline. Conclusions: Fatigue, QoL, and work and activity impairment improved following dupilumab initiation, though most patients did not achieve clinically relevant improvements. Effects on fatigue and work and activity impairment appear less pronounced compared with asthma symptom control, possibly due to irreversible impairments in some patients.</p