The relevance of depressive symptoms for the outcome of patients receiving vitamin K antagonists: results from the thrombEVAL cohort study

2020 ◽  
Author(s):  
Matthias Michal ◽  
Lisa Eggebrecht ◽  
Sebastian Göbel ◽  
Marina Panova-Noeva ◽  
Markus Nagler ◽  
...  
Keyword(s):  
Cohort Study ◽  
Depressive Symptoms ◽  
Vitamin K ◽  
Cox Regression ◽  
Vitamin K Antagonists ◽  
Independent Study ◽  
Prognostic Information ◽  
Cox Regression Analysis ◽  
Increased Risk ◽  
Patient Health

Abstract Aims Although depressive symptoms are highly prevalent in patients receiving oral anticoagulation (OAC), the relevance of depression for the outcome of anticoagulated individuals is unknown. Methods and results We analysed data from the multicentre cohort study thrombEVAL (NCT01809015) investigating the efficacy of OAC with vitamin K antagonists. There was an independent study monitoring, and an independent review panel assessed the endpoints. Out of n = 1558 participants, information about depressive symptoms, as measured by the two-item screener of the patient health questionnaire (PHQ-2), was available in n = 1405 individuals. The mean follow-up period was 28.04 months, with a standard deviation of 11.52 months. In multivariable Cox regression analysis, baseline PHQ-2 sum score was a strong and robust predictor of clinically relevant bleeding [hazard ratio (HR) 1.13, 95% confidence interval 1.03–1.24; P = 0.011] and all-cause mortality (HR 1.18, 1.08–1.28; P = 0.001) independent of age, sex, high school graduation, partnership, clinical profile, intake of serotonin reuptake inhibitors, and quality of OAC therapy. Individuals with clinically significant depressive symptoms (PHQ-2 ≥ 3) had a 57% increased risk for clinically relevant bleeding (fully adjusted HR 1.57, 1.08–2.28) and 54% greater risk for death (fully adjusted HR 1.54, 1.09–2.17). There was no association of depressive symptoms with thromboembolic events. For hospitalization, individuals with depressive symptoms (PHQ-2 ≥ 3) did not experience an elevated risk in the fully adjusted model (HR 1.08, 0.86–1.35; P = 0.52). Conclusion Assessment of depression by the PHQ-2 provided independent long-term prognostic information beyond common biomedical risk factors. These findings highlight the need for targeting depressive symptoms in the management of patients receiving OAC therapy.

High Soluble Thrombomodulin Is Associated with an Increased Risk of Major Bleeding during Treatment with Oral Anticoagulants: A Case–Cohort Study

2020 ◽  
Author(s):  
Myrthe M. A. Toorop ◽  
Nienke van Rein ◽  
Suzanne C. Cannegieter ◽  
Felix J. M. van der Meer ◽  
Pieter H. Reitsma ◽  
...  
Keyword(s):  
Cohort Study ◽  
Vitamin K ◽  
Major Bleeding ◽  
Cox Regression ◽  
Vitamin K Antagonists ◽  
Oral Anticoagulants ◽  
International Normalized Ratio ◽  
Soluble Thrombomodulin ◽  
Major Bleed ◽  
Increased Risk

Abstract Background Major bleeding occurs in 1 to 3% of patients treated with oral anticoagulants per year. Biomarkers may help to identify high-risk patients. A proposed marker for major bleeding while using anticoagulants is soluble thrombomodulin (sTM). Methods Plasma was available from 16,570 patients of the BLEEDS cohort that consisted of patients who started treatment with vitamin K antagonists between 2012 and 2014. A case–cohort study was performed including all patients with a major bleed (n = 326) during follow-up and a random sample of individuals selected at baseline (n = 652). Plasma sTM levels were measured and stratified by percentiles. Patients were also categorized by international normalized ratio (INR). Adjusted hazard ratios (for age, sex, hypertension, and diabetes) with 95% confidence intervals (CIs) were estimated by means of Cox regression. Results Plasma sTM levels were available for 263 patients with a major bleed and 538 control subjects. sTM levels were dose-dependently associated with risk of major bleeding, with a 1.9-fold increased risk (95% CI: 1.1–3.1) for levels above the 85th percentile versus the <25th percentile. A high INR (≥4) in the presence of high (≥70th percentile) sTM levels was associated with a 7.1-fold (95% CI: 4.1–12.3) increased risk of major bleeding, corresponding with a bleeding rate of 14.1 per 100 patient-years. Conclusion High sTM levels at the start of treatment are associated with major bleeding during vitamin K antagonist treatment, particularly in the presence of a high INR.

Subtherapeutic Anticoagulation Control under Treatment with Vitamin K-Antagonists—Data from a Specialized Coagulation Service

2019 ◽  
Vol 119 (08) ◽  
pp. 1347-1357 ◽  
Author(s):  
Jürgen H. Prochaska ◽  
Christoph Hausner ◽  
Markus Nagler ◽  
Sebastian Göbel ◽  
Lisa Eggebrecht ◽  
...  
Keyword(s):  
Risk Factors ◽  
Vitamin K ◽  
Cox Regression ◽  
Statistical Significance ◽  
Vitamin K Antagonists ◽  
International Normalized Ratio ◽  
Living Alone ◽  
Cox Regression Analysis ◽  
Increased Risk ◽  
Anticoagulation Control

AbstractIn contrast to overanticoagulation, evidence on risk factors and outcome of subtherapeutic oral anticoagulation (OAC) with vitamin K-antagonists (VKAs) under optimum care is limited. We investigated the clinical phenotype, anticoagulation control, and clinical outcome of 760 VKA patients who received OAC therapy by a specialized coagulation service in the thrombEVAL study (NCT01809015). During 281,934 treatment days, 278 patients experience ≥ 1 episode of subtherapeutic anticoagulation control and had lower quality of OAC therapy compared to 482 patients without subtherapeutic international normalized ratio: 67.6%, interquartile range (IQR) 54.9%/76.8% versus 81.0%, IQR 68.5%/90.4%; p < 0.001. In Cox regression analysis with adjustment for age, sex, cardiovascular risk factors, comorbidities, and treatment characteristics, female sex (hazard ratio [HR], 1.4, 95% confidence interval [CI], 1.0/1.9; p = 0.03), diabetes (HR, 1.4, 95% CI, 1.0/2.0; p = 0.03), and living alone (HR, 1.5, 95% CI, 1.1/2.1; p = 0.009) were independent risk factors of subtherapeutic anticoagulation control, whereas atrial fibrillation (HR, 0.6, 95% CI, 0.4/0.9; p = 0.02) and self-management of OAC therapy (HR, 0.2, 95% CI, 0.1/0.6; p = 0.001) were protective. In addition, active smoking (HR, 1.7, 95% CI, 0.9/3.0; p = 0.086) and living in a nursing home (HR, 1.6, 95% CI, 0.8/3.2; p = 0.15) indicated an elevated risk at the borderline of statistical significance. For the prediction of recurrent subtherapeutic anticoagulation, living alone was the only independent risk factor (HR, 1.7, 95% CI, 1.1/2.5; p = 0.013). The present study suggests that women, diabetics, and patients living alone experience an increased risk of low-quality VKA therapy and might potentially benefit from treatment with direct-acting anticoagulants.

scholarly journals Do Children With Constipation Have Increased Risk of Asthma? Real-World Data From a Nationwide Population-Based Cohort Study

2021 ◽  
Vol 9 ◽  
Author(s):  
Yen-Chu Huang ◽  
Meng-Che Wu ◽  
Yu-Hsun Wang ◽  
James Cheng-Chung Wei
Keyword(s):  
Cohort Study ◽  
Cox Regression ◽  
Population Based ◽  
Hazard Ratio ◽  
Adjusted Hazard Ratio ◽  
Research Database ◽  
Real World Data ◽  
Childhood Disorders ◽  
Cox Regression Analysis ◽  
Increased Risk

Background: Asthma is one of the most burdensome childhood disorders. Growing evidence disclose intestinal dysbiosis may contribute to asthma via the gut-lung axis. Constipation can lead to alteration of the gut microbiota. The clinical impact of constipation on asthma has not been researched. Therefore, we aim to assess whether pediatric constipation influence the risk of developing asthma by a nationwide population-based cohort study.Methods: We analyzed 10,363 constipated patients and 10,363 individuals without constipation between 1999 and 2013 from Taiwan's National Health Insurance Research Database. Analysis of propensity score was utilized to match age, sex, comorbidities, and medications at a ratio of 1:1. In addition, multiple Cox regression analysis was performed to evaluate the adjusted hazard ratio of asthma. Furthermore, sensitivity tests and a stratified analysis were performed.Results: After adjustment for age, sex, comorbidities, and medications, constipated patients had a 2.36-fold greater risk of asthma compared to those without constipation [adjusted hazard ratio (aHR): 2.36, 95% C.I. 2.04–2.73, p &lt; 0.001]. Furthermore, the severity of constipation is associated with an increased risk of asthma; the adjusted hazard ratio was 2.25, 2.85, and 3.44 within &lt; 3, 3–12, and ≥12 times of laxatives prescription within 1 year, respectively (p &lt; 0.001).Conclusion: Constipation was correlated with a significantly increased risk of asthma. Pediatricians should be aware of the possibility of asthma in constipated patients. Further research is warranted to investigate the possible pathological mechanisms of this association.

Headache as a risk factor for dementia: A prospective population-based study

Cephalalgia ◽  
2013 ◽  
Vol 34 (5) ◽  
pp. 327-335 ◽  
Author(s):  
Knut Hagen ◽  
Eystein Stordal ◽  
Mattias Linde ◽  
Timothy J Steiner ◽  
John-Anker Zwart ◽  
...  
Keyword(s):  
Risk Factor ◽  
Cohort Study ◽  
Cox Regression ◽  
Subsequent Development ◽  
Population Based ◽  
Health Study ◽  
Cox Regression Analysis ◽  
Hazard Ratios ◽  
Increased Risk

Background Headache has not been established as a risk factor for dementia. The aim of this study was to determine whether any headache was associated with subsequent development of vascular dementia (VaD), Alzheimer’s disease (AD) or other types of dementia. Methods This prospective population-based cohort study used baseline data from the Nord-Trøndelag Health Study (HUNT 2) performed during 1995–1997 and, from the same Norwegian county, a register of cases diagnosed with dementia during 1997–2010. Participants aged ≥20 years who responded to headache questions in HUNT 2 were categorized (headache free; with any headache; with migraine; with nonmigrainous headache). Hazard ratios (HRs) for later inclusion in the dementia register were estimated using Cox regression analysis. Results Of 51,383 participants providing headache data in HUNT 2, 378 appeared in the dementia register during the follow-up period. Compared to those who were headache free, participants with any headache had increased risk of VaD ( n = 63) (multivariate-adjusted HR = 2.3, 95% CI 1.4–3.8, p = 0.002) and of mixed dementia (VaD and AD ( n = 52)) (adjusted HR = 2.0, 95% CI 1.1–3.5, p = 0.018). There was no association between any headache and later development of AD ( n = 180). Conclusion In this prospective population-based cohort study, any headache was a risk factor for development of VaD.

scholarly journals Bleeding and thromboembolism due to drug-drug interactions with non-vitamin K antagonist oral anticoagulants—a Swedish, register-based cohort study in atrial fibrillation outpatients

2020 ◽  
Author(s):  
Johan Holm ◽  
Buster Mannheimer ◽  
Rickard E Malmström ◽  
Erik Eliasson ◽  
Jonatan D Lindh
Keyword(s):  
Atrial Fibrillation ◽  
Cohort Study ◽  
Ischemic Stroke ◽  
Vitamin K ◽  
Cox Regression ◽  
Oral Anticoagulants ◽  
Outcome Data ◽  
Vitamin K Antagonist ◽  
Drug Register ◽  
Increased Risk

Abstract Purpose To study the association between interacting drugs and bleeding or thromboembolism in atrial fibrillation outpatients treated with non-vitamin K antagonist oral anticoagulants (NOACs). Methods Population-based cohort study of outpatients treated with NOACs in Sweden from 2008 to 2017. Patients with atrial fibrillation and newly initiated NOAC treatment were identified in the Prescribed Drug Register. Comorbidities and outcome data were retrieved from the Patient Register and the Cause of Death Register. Cox-regression analyses were performed to evaluate the primary endpoints any severe bleed and ischemic stroke/transient ischemic attack/stroke unspecified during the first six months of treatment. Secondary endpoints were gastrointestinal bleeding, intracranial bleeding, ischemic stroke, and venous thromboembolism. Results Increased risk of any severe bleed was found when NOAC treatment, and drugs with pharmacodynamic effect on bleeding were combined, compared to NOAC only. An increased risk with these combinations was evident for apixaban (hazard ratio (HR) 1.47; 95% CI 1.33–1.63), rivaroxaban (HR 1.7; 95% CI 1.49–1.92), and dabigatran (HR 1.26; 95% CI 1.05–1.52). For apixaban, there was an increased risk of any severe bleed when combined with CYP3A4 and/or P-glycoprotein (P-gp) inhibitors (HR 1.23; 95% CI 1.01–1.5). The use of inducers of CYP3A4 and/or P-gp was low in this cohort, and effects on ischemic stroke/TIA/stroke unspecified could not be established. Conclusion Increased risk of bleeding was seen for pharmacodynamic and pharmacokinetic interactions with NOACs. Prescribers need to be vigilant of the effect of interacting drugs on the risk profile of patients treated with NOACs.

scholarly journals Increased risk of stroke in patients with diffuse idiopathic skeletal hyperostosis: a nationwide population-based cohort study

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Yuan-Yang Cheng ◽  
Ching-Heng Lin ◽  
Po-Yi Tsai ◽  
Yi-Huei Chen ◽  
Shih-Yi Lin ◽  
...  
Keyword(s):  
Cohort Study ◽  
Cerebrovascular Disease ◽  
Cox Regression ◽  
Incidental Finding ◽  
Diffuse Idiopathic Skeletal Hyperostosis ◽  
Hazard Ratio ◽  
Control Group ◽  
Medical Database ◽  
Cox Regression Analysis ◽  
Increased Risk

AbstractDiffuse idiopathic skeletal hyperostosis (DISH) is frequently an incidental finding during X-ray examination. Although it has been shown to be associated with several chronic diseases, the hazard of cerebrovascular disease has seldom been explored. Our study aimed at determining the risk of stroke conferred by DISH, which is a retrospective cohort study adopting the largest medical database in Taiwan. Patients with a diagnosis of DISH at least three times from 2005 to 2010 were identified as the study group, and those in the control group were selected by matching age and gender. Patients were followed up until the end of 2015 to trace the incidence of stroke. Cox regression analysis was performed to compute the hazard ratio of stroke. Among the included 5300 patients, 1060 had a diagnosis of DISH. Significantly higher prevalence rates of stroke, hypertension, diabetes, and hyperlipidemia were noted in these patients. Overall, DISH conferred a 1.68 times higher risk of developing stroke. The significantly higher hazard ratio could be identified in both genders whether hypertension existed or not. Even in those without comorbidities, DISH still conferred a significantly higher risk of cerebrovascular disease in the future, which should never be ignored when encountered during clinical practice.

scholarly journals Selective serotonin reuptake inhibitor use is associated with major bleeding during treatment with vitamin K antagonists: results of a cohort study

2021 ◽  
Author(s):  
Sanne Bakker ◽  
Louise Burggraaf ◽  
MJHA Kruip ◽  
Felix van der Meer ◽  
WM Lijfering ◽  
...  
Keyword(s):  
Vitamin K ◽  
Major Bleeding ◽  
Serotonin Reuptake ◽  
Selective Serotonin Reuptake Inhibitors ◽  
Cox Regression ◽  
Conditional Logistic Regression ◽  
Vitamin K Antagonists ◽  
Selective Serotonin ◽  
Bleeding Complications ◽  
Increased Risk

Aims: To determine whether Selective serotonin reuptake inhibitors (SSRIs) cause major bleeding during vitamin K antagonist (VKA) treatment and investigate the possible mechanisms behind this interaction. Methods: Information on SSRI use and bleeding complications was obtained from patient records at the Anticoagulation Clinics of Leiden and Rotterdam of VKA initiators between 2006 and 2018. Conditional logistic regression and time-dependent Cox regression were used to estimate the effect of SSRIs on a high INR (≥ 5) within 2 months after SSRI initiation and on major bleeding during the entire period of SSRI use, respectively. SSRI use was stratified for (non-)CYP2C9 inhibitors. Results: 58,918 patients were included, of whom 1504 were SSRI users. SSRI initiation versus non-use was associated with a 2.41-fold (95% confidence interval [CI] 2.01-2.89) increased risk for a high INR, which was 3.14-fold (95%CI 1.33-7.43) among CYP2C9 inhibiting SSRIs. SSRI use versus non-use was associated with a 1.22-fold (95%CI 0.99-1.50) increased risk for major bleeding in all SSRI users, which was 1.31-fold (95%CI 0.62-2.72) in CYP2C9 inhibiting SSRIs compared to non-users. Conclusion: SSRIs are associated with an increased risk of high INR and major bleeding. These risks were slightly more elevated for CYP2C9 inhibiting SSRI users, suggesting that this was due to a pharmacokinetic interaction (by CYP2C9 inhibition) as well as a pharmacodynamic effect of SSRIs on platelet activation.

scholarly journals Accelerometer-derived sedentary time and physical activity and the incidence of depressive symptoms – The Maastricht Study

2020 ◽  
pp. 1-8
Author(s):  
Magdalena J. Konopka ◽  
Sebastian Köhler ◽  
Coen D. A. Stehouwer ◽  
Nicolaas C. Schaper ◽  
Ronald M. A. Henry ◽  
...  
Keyword(s):  
Physical Activity ◽  
Depressive Symptoms ◽  
Sex Education ◽  
Sedentary Time ◽  
Cox Regression ◽  
Future Research ◽  
Cox Regression Analysis ◽  
Increased Risk ◽  
Intensity Physical Activity

Abstract Background This study examined the associations between accelerometer-derived sedentary time (ST), lower intensity physical activity (LPA), higher intensity physical activity (HPA) and the incidence of depressive symptoms over 4 years of follow-up. Methods We included 2082 participants from The Maastricht Study (mean ± s.d. age 60.1 ± 8.0 years; 51.2% men) without depressive symptoms at baseline. ST, LPA and HPA were measured with the ActivPAL3 activity monitor. Depressive symptoms were measured annually over 4 years of follow-up with the 9-item Patient Health Questionnaire (PHQ-9). Cox regression analysis was performed to examine the associations between ST, LPA, HPA and incident depressive symptoms (PHQ-9 ⩾ 10). Analyses were adjusted for total waking time per day, age, sex, education level, type 2 diabetes mellitus, body mass index, total energy intake, smoking status and alcohol use. Results During 7812.81 person-years of follow-up, 203 (9.8%) participants developed incident depressive symptoms. No significant associations [Hazard Ratio (95% confidence interval)] were found between sex-specific tertiles of ST (lowest v. highest tertile) [1.13 (0.76–1.66], or HPA (highest v. lowest tertile) [1.14 (0.78–1.69)] and incident depressive symptoms. LPA (highest v. lowest tertile) was statistically significantly associated with incident depressive symptoms in women [1.98 (1.19–3.29)], but not in men (p-interaction <0.01). Conclusions We did not observe an association between ST or HPA and incident depressive symptoms. Lower levels of daily LPA were associated with an increased risk of incident depressive symptoms in women. Future research is needed to investigate accelerometer-derived measured physical activity and ST with incident depressive symptoms, preferably stratified by sex.

Prognostic Significance of Chromosome Aberrations in High-Grade Soft Tissue Sarcomas

2006 ◽  
Vol 24 (2) ◽  
pp. 315-320 ◽  
Author(s):  
Fredrik Mertens ◽  
Ulf Strömberg ◽  
Anders Rydholm ◽  
Pelle Gustafson ◽  
Henrik C.F. Bauer ◽  
...  
Keyword(s):  
Soft Tissue ◽  
Chromosome Aberrations ◽  
Cox Regression ◽  
Prognostic Significance ◽  
Soft Tissue Sarcomas ◽  
Tumor Grade ◽  
High Grade ◽  
Prognostic Information ◽  
Cox Regression Analysis ◽  
Increased Risk

Purpose To investigate whether previously observed correlations between tumor karyotype and risk of metastases could be reproduced in an independent set of high-grade soft tissue sarcomas (STSs). Patients and Methods In a previous study on high-grade STSs with clonal chromosome aberrations, we identified a number of cytogenetic variables, besides tumor grade and size, that were associated with significantly increased risk of metastases. In the present study, we have tested the predictive value of these cytogenetic variables in a new set of 156 high-grade STSs, all located in the extremities or trunk wall. Results Of the 10 cytogenetic variables that turned out to provide prognostic information in the previous series, encompassing 122 trunk wall or extremity STSs, three were significantly associated with metastases also in the new series. In a final Cox regression analysis including these three cytogenetic variables, as well as tumor grade and size, on the combined series of 278 high-grade STSs, four parameters were found to be significantly associated with metastasis risk: tumor grade 3, tumor size ≥ 5 cm, breakpoint in region 1p1, and gain of region 6p1. Conclusion Our findings suggest that independent prognostic information may be gained from cytogenetic analysis of high-grade STS.

scholarly journals Chronic Periodontitis Is Associated with the Risk of Bipolar Disorder: A Population-Based Cohort Study

2020 ◽  
Vol 17 (10) ◽  
pp. 3466
Author(s):  
Yung-Kai Huang ◽  
Yu-Hsun Wang ◽  
Yu-Chao Chang
Keyword(s):  
Bipolar Disorder ◽  
Cohort Study ◽  
Chronic Periodontitis ◽  
Cox Regression ◽  
Population Based ◽  
Cox Proportional Hazards ◽  
Etiologic Factor ◽  
Research Database ◽  
Cox Regression Analysis ◽  
Increased Risk

Bipolar disorder (BD) is a psychiatric mood disturbance manifested by manic, hypomanic, or major depressive periods. Chronic inflammation was evidenced as an important etiologic factor of BD. Chronic periodontitis (CP) is an inflammatory disease triggered by bacterial products, leading to the destruction of periodontium. The relationship between BD and CP is of interest to investigate. Therefore, a nationwide population-based cohort study was used to investigate the risk of BD and CP exposure from 2001 to 2012. We identified 61,608 patients with CP from the Taiwanese National Health Insurance Research Database (NHIRD). The 123,216 controls were randomly captured and matched by age, sex, index year, and co-morbidities. The association between CP exposure and BD risk was examined by Cox proportional hazards regression models. In this study, 61,608 CP patients and 123,216 controls were followed up for 7.45 and 7.36 years, respectively. In total, 138 BD patients were identified in the CP cohort and 187 BD cases were found in the non-CP cohort. The incidence rate of BD was significantly higher in the CP cohort than in the non-CP cohort (adjusted HR: 1.46, 95% CI: 1.17–1.81) according to the multivariate Cox regression analysis. Females had a 1.47-fold increased risk (95% CI: 1.16–1.86) for BD compared to males. Taken together, CP may be associated with an increased risk of subsequent BD in Taiwan.

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