Abstract W MP65: Moderate to Severe Left Atrial Enlargement is Associated with Cardioembolic or Cryptogenic Stroke Recurrence in a Multiethnic Cohort: The Northern Manhattan Study

Stroke ◽  
2015 ◽  
Vol 46 (suppl_1) ◽  
Author(s):  
Shadi Yaghi ◽  
Yeseon P Moon ◽  
Consuelo Mora-McLaughlin ◽  
Joshua Z Willey ◽  
Marco R Di Tullio ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Ischemic Stroke ◽  
Left Atrial ◽  
Recurrent Stroke ◽  
Cryptogenic Stroke ◽  
Cardioembolic Stroke ◽  
Stroke Recurrence ◽  
Stroke Patients ◽  
Stroke Subtypes ◽  
Multiethnic Cohort

Background: While left atrial (LA) enlargement increases incident stroke risk, the association with recurrent stroke is unclear. Our aim was to determine the association of LA enlargement (LAE) with stroke recurrence risk and recurrent stroke subtypes likely related to embolism (cryptogenic or cardioembolic). Methods: We enrolled 655 first ischemic stroke patients in the Northern Manhattan Stroke Study. LA size was measured by two-dimensional echocardiogram as part of the clinical evaluation and patients were followed annually for up to 5 years. LA size adjusted for sex and body surface area was categorized into three groups: normal (52.7%), mild LAE (31.6%), and moderate to severe LAE (15.7%). The outcomes were total recurrent stroke, and recurrent combined cryptogenic or cardioembolic stroke. Cox proportional hazard models assessed the association between LA size and risk of stroke recurrence. Results: Of 655 patients, LA size data was present in 529 (81%). Mean age was 69 ± 13 years; 46% were male and 18% had atrial fibrillation. Over a median of 4 years, recurrent stroke occurred in 83 patients (16%), 29 were cardioembolic or cryptogenic stroke. After adjusting for baseline demographics and risk factors including atrial fibrillation and congestive heart failure, compared to normal LA size, moderate to severe LAE was associated with greater risk of recurrent combined cardioembolic or cryptogenic stroke (adjusted HR 2. 99, 95% CI 1. 10 to 8.13), but not with risk of total stroke recurrence (adjusted HR 1.18, 95% CI 0.60 to 2.32). Mild LAE was not associated with either total stroke recurrence or the combined recurrent cryptogenic or cardioembolic stroke subtypes. Conclusion: Moderate to severe LAE is an independent marker of recurrent cardioembolic or cryptogenic stroke in a multiethnic cohort of ischemic stroke patients. Future research is needed to determine if anticoagulant use reduces the risk of recurrence in ischemic stroke patients with moderate to severe LAE.

Abstract WP256: Atrial Fibrillation Predicting Factors in Transient and Minor Stroke Patients

Stroke ◽  
2020 ◽  
Vol 51 (Suppl_1) ◽  
Author(s):  
Marian Muchada Lopez ◽  
Jorge Pagola ◽  
Jesus Juega ◽  
Jaume Francisco-Pascual ◽  
Alejandro Bustamante ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Ischemic Stroke ◽  
Left Atrial ◽  
Cryptogenic Stroke ◽  
Volume Index ◽  
Minor Stroke ◽  
Stroke Patients ◽  
Left Atrial Strain ◽  
Minor Ischemic Stroke ◽  
Atrial Strain

Introduction and Purpose: Our aim was to review the characteristics of transient ischemic attack (TIA) and minor ischemic stroke patients monitored for atrial fibrillation (AF) epidoses detection within the first 4weeks after stroke to assess AF predictors. Materials and Methods: TIA and minor ischemic stroke patients (nihss≤ 5) were selected from CRYPTO-AF database. CRYPTO-AF is a prospective multicentre registry of patients with cryptogenic stroke older of 55 year-old. Monitoring started within the first 72 hours from stroke symptoms onset and was prolonged for 4 weeks. Clinical, cardiographic and blood test parameters of patients included were reviewed. Fisher exact and Mann Whitney tests were used to analyze categorical and continuous data. Results: In our cohort of 152 transient and minor ischemic stroke patients, 55.9% were men, mean age 73.18±10.24 and median NIHSS score was 2.31(0-5). A total of 30 patients (20.3%) were diagnosed with AF in the first month of monitoring, 6 patients (5.7%) within the first 3 days, 14 patients (13.3%) between 3 days and to 2 weeks of monitoring, and 14 partientes (12.4%) between the second and the fourth week. In these transient and minor ischemic stroke patients, age (p< 0.031), left atrial volume index (p< 0.023), the appearance of isolated extrasystoles during monitoring (p< 0.021), Type B natriuretic peptide (p< 0.011) and the longitudinal strain (p< 0.019) appeared as independet precitors of AF. However in the multivariate analysis adjusted for the above variables, only left atrial strain (OR 0.89, 95% CI: 0.797-0.991, p< 0.034) independently predicts AF detection. Conclusions: In our serie, only the left atrial strain appeared as a indepent predictor of AF. Given the known pathophysiology of TIA and minor ischemic stroke, the description of AF predictors would help to identify those patients who would benefit from completing a longer monitoring. More studies are needed to identify these predictors.

Abstract WMP64: Utility of Left Atrial Abnormality on Admission Electrocardiography in Acute Ischemic Stroke

Stroke ◽  
2017 ◽  
Vol 48 (suppl_1) ◽  
Author(s):  
Yukio Sugiyama ◽  
Nobuyuki Ohara ◽  
Kotaro Watanabe ◽  
Junya Kobayashi ◽  
Daisuke Takahashi
Keyword(s):  
Atrial Fibrillation ◽  
Ischemic Stroke ◽  
Acute Ischemic Stroke ◽  
Left Atrial ◽  
Strong Predictor ◽  
Multiple Logistic Regression Analysis ◽  
Cryptogenic Stroke ◽  
P Wave ◽  
Cardioembolic Stroke ◽  
Ecg Monitoring

Introduction and Hypothesis: Clinical categorization of ischemic stroke is very important to select the antithrombotic therapy for preventing the recurrent stokes. However, about 25% of ischemic stroke is the stroke for undetermined cause, termed as cryptogenic stroke. Recently, proactive detecting of paroxysmal atrial fibrillation (PAF) in cryptogenic stroke has gained attention. P-wave terminal force in lead V1 (PTFV1) of electrocardiography (ECG) is a specific indicator of left atrial abnormality. In this study, we tested PTFV1 for the utility of PAF detection and further clinical categorization in acute ischemic stroke. Methods: One hundred forty eight consecutive acute ischemic stroke patients were admitted to our hospital from September 2014 to March 2016. We included 105 patients (mean age 72.8±13.4 years), who had sinus rhythm on admission 12-lead ECG without atrial fibrillation, or cardiac pacing. PTFV1 (mmхsec) of participants was assessed, and had analyzed the association with PAF detection in a 24-hour ECG monitoring and clinical categories of ischemic stroke. Results: PTFV1 was significantly higher in the patients with PAF (n=11) than in those without PAF (0.049±0.024 vs 0.031±0.027; p<0.05). Multiple logistic regression analysis revealed that PTFV1 was an independent predictor for PAF detection (odds ratio, 1.46; 95% confidence interval, 1.02-2.08; p<0.05). According to the clinical categorization, PTFV1 of cardioembolic stroke (0.061±0.022) was significantly higher, compared to lacunar stroke (0.018±0.019; p<0.01), atherothrombotic stroke (0.035±0.026; p<0.05), and cryptogenic stroke (0.031±0.029; p<0.05). The proportion of patients with left atrial abnormality defined by PTFV1 (≧0.04), was 10 out of 11 (91%) for cardioembolic stroke, and 10 out of 27 (37%) for cryptogenic stroke. Conclusions: PTFV1 on admission ECG in acute ischemic stroke was a strong predictor for PAF detection and cardioembolic stroke diagnosis. Extended ECG monitoring may be useful in cryptogenic stroke with left atrial abnormality defined by PTFV1.

Abstract P709: Risk Factors Associated With Atrial Fibrillation Detection by Mobile Cardiac Outpatient Telemetry Following Acute Ischemic Stroke

Stroke ◽  
2021 ◽  
Vol 52 (Suppl_1) ◽  
Author(s):  
Ovais Inamullah ◽  
Alec McConnell ◽  
Hussein Al-khalidi ◽  
Gerald S Bloomfield ◽  
Shreyansh Shah
Keyword(s):  
Atrial Fibrillation ◽  
Ischemic Stroke ◽  
Acute Ischemic Stroke ◽  
Patient Selection ◽  
Left Atrial ◽  
Cryptogenic Stroke ◽  
Left Ventricular ◽  
Stepwise Logistic Regression ◽  
Internal Diameter ◽  
Atrial Area

Background: Mobile Cardiac outpatient telemetry (MCOT) is often used for patients (pts) with cryptogenic ischemic stroke following hospital discharge to detect atrial fibrillation (AFib) but criteria for patient selection remains a subject of debate. Methods: We identified 297 pts hospitalized with acute ischemic stroke who had an inpatient transthoracic echocardiogram (TTE) and underwent MCOT upon discharge between 2016 and 2018 at a large academic comprehensive stroke center. Pts characteristics between AFib vs. no AFib were compared by Fisher’s exact test for categorical and Wilcoxon rank-sum test for continuous variables. A multivariable stepwise logistic regression model was developed to determine the predictors of AFib detection. Statistical hypotheses were tested as two-sided at 0.05 level of significance. Results: Of the 297 pts, AFib was detected in 24 (8.1%) on 30-day MCOT. Pts with AFib detected were older, white, and have had a larger left atrial area (Table). The final logistic model demonstrated that white race (vs. non-white) (OR 4.86, 1.53-15.41), left atrial area (OR 1.15, 1.05-1.25) and left ventricular internal diameter in diastole (OR 0.33, 0.16-0.67) were associated with AFib detection by MCOT. Conclusion: Although rates of AFib detection on 30-day MCOT post-discharge was low, there are important patient characteristics and TTE features that can improve patient selection. Further studies are needed to determine if this data can be used prospectively to clinically decide which pts with cryptogenic stroke should be given 30-day MCT to detect atrial fibrillation.

Abstract P132: Clinical Outcomes In Ischemic Stroke Patients With Uncontrolled Hypertension

Hypertension ◽  
2021 ◽  
Vol 78 (Suppl_1) ◽  
Author(s):  
Zahra Abuzaid ◽  
Sara Almuslem ◽  
Farah Aleisa
Keyword(s):  
Blood Pressure ◽  
Ischemic Stroke ◽  
Clinical Outcomes ◽  
Recurrent Stroke ◽  
Uncontrolled Hypertension ◽  
Stroke Recurrence ◽  
Stroke Patients ◽  
Stroke Event ◽  
Uncontrolled Blood Pressure

Background: Hypertension is considered major risk factor for incidence of ischemic stroke, controlling blood pressure reduces this risk, the relationship of uncontrolled blood pressure and stroke outcomes is complex, post stroke uncontrolled blood pressure remains one of the major contributing factors for stroke recurrence and mortality, in our study we studied the long term effects of uncontrolled hypertension in modern health care setting. Methodology: Patients in the study were admitted to the neurology department at KFSH-D between March 2015- August 2019, we included 102 acute ischemic stroke patients whom had hypertension, all patients had follow up appointments at stroke clinic a minimum of 2 visits over 4 years. We retrospectively compared blood pressure data from stroke patients with recurrent ischemic stroke events vs. patients with initial stroke event, and recurrent stroke, also we studied blood pressure readings for different stroke severity groups, patients who had severe stroke with mRS>4, compared to milder stroke group of mRS<4. Results: We found 48 patients identified with recurrent stroke event, those with uncontrolled hypertension had significantly higher stroke recurrence events (P=0.002), despite acute stroke treatment, patients who had history of uncontrolled hypertension were found to have more severe stroke deficits than those who had controlled blood pressure (P=0.029). We found significant difference in the long term stroke clinical outcomes between patients who had uncontrolled blood pressure and patients who had controlled blood pressure recordings within the same hospital setting (P=0.064). Conclusion: Based on our findings, uncontrolled hypertension was associated with higher risk of stroke recurrence, it also increased susceptibility to worse stroke clinical outcomes up to 1 year after initial stroke event, which deserved further close attention and better blood pressure control.

scholarly journals Relation Between Left Atrial Enlargement and Stroke Subtypes in Acute Ischemic Stroke Patients

2013 ◽  
Vol 15 (3) ◽  
pp. 131 ◽  
Author(s):  
Hye-Young Shin ◽  
In-Hye Jeong ◽  
Chang-Ki Kang ◽  
Dong-Jin Shin ◽  
Hyeon-Mi Park ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Acute Ischemic Stroke ◽  
Left Atrial ◽  
Stroke Patients ◽  
Left Atrial Enlargement ◽  
Stroke Subtypes ◽  
Atrial Enlargement

Cancer-Associated Hypercoagulation Increases the Risk of Early Recurrent Stroke in Patients with Active Cancer

2018 ◽  
Vol 46 (1-2) ◽  
pp. 46-51 ◽  
Author(s):  
Jun Fujinami ◽  
Tomoyuki Ohara ◽  
Fukiko Kitani-Morii ◽  
Yasuhiro Tomii ◽  
Naoki Makita ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Acute Ischemic Stroke ◽  
Recurrent Stroke ◽  
Stroke Recurrence ◽  
Multivariable Logistic Regression Analysis ◽  
Stroke Patients ◽  
Recurrent Cancer ◽  
Systemic Metastasis ◽  
D Dimer ◽  
Active Cancer

Background: This study assessed the incidence and predictors of short-term stroke recurrence in ischemic stroke patients with active cancer, and elucidated whether cancer-associated hypercoagulation is related to early recurrent stroke. Methods: We retrospectively enrolled acute ischemic stroke patients with active cancer admitted to our hospital between 2006 and 2017. Active cancer was defined as diagnosis or treatment for any cancer within 12 months before stroke onset, known recurrent cancer or metastatic disease. The primary clinical outcome was recurrent ischemic stroke within 30 days. Results: One hundred ten acute ischemic stroke patients with active cancer (73 men, age 71.3 ± 10.1 years) were enrolled. Of those, recurrent stroke occurred in 12 patients (11%). When patients with and without recurrent stroke were compared, it was found that those with recurrent stroke had a higher incidence of pancreatic cancer (33 vs. 10%), systemic metastasis (75 vs. 39%), multiple vascular territory infarctions (MVTI; 83 vs. 40%), and higher ­D-dimer levels (16.9 vs. 2.9 µg/mL). Multivariable logistic regression analysis showed that each factor mentioned above was not significantly associated with stroke recurrence independently, but high D-dimer (hDD) levels (≥10.4 µg/mL) and MVTI together were significantly associated with stroke recurrence (OR 6.20, 95% CI 1.42–30.7, p = 0.015). Conclusions: Ischemic stroke patients with active cancer faced a high risk of early recurrent stroke. The concurrence of hDD levels (≥10.4 µg/mL) and MVTI was an independent predictor of early recurrent stroke in active cancer patients. Our findings suggest that cancer-associated hypercoagulation increases the early recurrent stroke risk.

scholarly journals Study of Outcome of Ischemic Stroke Patient With Atrial Fibrillation

2018 ◽  
Vol 28 (2) ◽  
pp. 1-6
Author(s):  
Achinta Kumar Mallick ◽  
Md Kafil Uddin ◽  
Md Ahmed Ali ◽  
Pijus Kumar Kundu ◽  
Sheikh Mohammad Emdadul Haque ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Risk Factor ◽  
Ischemic Stroke ◽  
Linear Regression Analysis ◽  
Clinical Deterioration ◽  
Stroke Recurrence ◽  
Stroke Severity ◽  
Multivariate Linear Regression Analysis ◽  
Stroke Patients

Atrial fibrillation (AF) is a common arrhythmia and a major risk factor for ischemic stroke, especially in the elderly. Patients with nonvalvular AF have a 5-fold excess risk of stroke. However, population-based data are scarce in patients who have experienced a first-ever ischemic stroke in the presence of AF regarding long-term risk of stroke recurrence and case-fatality rate. Aim of the study is to find out the outcome of ischemic stroke patients with Atrial Fibrillation. It was a descriptive type cross sectional study where 125 diagnosed cases of ischemic stroke were included. Presence of atrial fibrillation was detected by electrocardiogram. They were divided into two groups – those with atrial fibrillation and those without. Comparison was done between the two group in term of recurrence, mortality and clinical improvement. Atrial fibrillation was present in 22 (17.6%) of 125 patients with ischemic stroke. Those with AF were more frequently male, aged 45 years and older. The presence of AF was associated with high 3 months (Χ2 =4.562, df = 1, p<0.05) and 6 months mortality (Χ2 =7.868, df = 1, p<0.05), with a higher stroke recurrence rate within the first 6 months follow-up (22.7% versus 7.8% (<0.05)). At 3 months follow up clinical deterioration was noted in 9.1% patient with atrial fibrillation compared to 2.9% patients who had no arrhythmia(p<0.01) and at 6 months follow up clinical deterioration was noted in 18.2% patient with atrial fibrillation compared to 4.9% patients who had no arrhythmia(p<0.01). Ischemic stroke patients with atrial fibrillation had significant mortality within the study period compared to those without atrial fibrillation. Significant deterioration in clinical outcome was noted in atrial fibrillation group after six months. Recurrence was more in ischemic stroke patients with atrial fibrillation. Multivariate linear regression analysis shows atrial fibrillation as well as CKD, Diabetes mellitus and smoking as independent risk factor for recurrence. In conclusion, patients who had an ischemic stroke with accompanying atrial fibrillation had higher mortality, grave stroke severity, more recurrences and poorer functional status than those without atrial fibrillation.TAJ 2015; 28(2): 1-6

scholarly journals Karakteristik dan Periode Kekambuhan Stroke pada Pasien dengan Stroke Berulang di Rumah Sakit Margono Soekardjo Purwokerto Kabupaten Banyumas

2018 ◽  
Vol 3 (1) ◽  
Author(s):  
Meida Laely Ramdani
Keyword(s):  
Ischemic Stroke ◽  
Secondary Prevention ◽  
Low Income ◽  
Recurrent Stroke ◽  
Sampling Technique ◽  
Stroke Recurrence ◽  
Stroke Patients ◽  
Cross Sectional ◽  
Post Stroke ◽  
Duration Of Illness

Background: Patients who had stroke recurrence after the first stroke have a high risk of disability as well as high rates of morbidity and mortality. Incidence of stroke recurrence can be prevented by controlling risk factors and secondary prevention among post stroke patient, and also tent of the duration of the occurrence of recurrent stroke after the first attack. Objective: The purpose of this study was to determine the characteristics and stroke recurrence periods of post stroke patients.Methods: Cross sectional study design was used in this study. Total 73 recurrent stroke patients age 18-60 years old were selected using consecutive sampling technique. This study was conducted on patients during their follow up in the outpatient department of unit neurology, Margono Soekardjo Purwokerto Hospital during November-December 2015. The characteristics of the recurrent stroke patients include sex, age, education, occupation, and income. This study also describes type of stroke and duration of illness. The periods of recurrent stroke patients divided in to three time periods (≤ 6-month, 7-12 month, >12 month). Results: 73 recurrent stroke patients showed 56% were female, age group 39-60 years old was 97,5%, 60,3% have low education (below senior high school), 64,7% work as public and private employees. Income of respondents were low income 53,4%. Ischemic stroke was the majority (87,7%), no history family of stroke 64,4%, 1-5 years duration of illness and periods of stroke recurrence >12 month was 45,20%.Conclusion:  Ischemic stroke is the biggest case of recurrent stroke, so that we need to emphasize the importance of secondary prevention including medication and treatment. Background: Patients who had stroke recurrence after the first stroke have a high risk of disability as well as high rates of morbidity and mortality. Incidence of stroke recurrence can be prevented by controlling risk factors and secondary prevention among post stroke patient, and also tent of the duration of the occurrence of recurrent stroke after the first attack. Objective: The purpose of this study was to determine the characteristics and stroke recurrence periods of post stroke patients.Methods: Cross sectional study design was used in this study. Total 73 recurrent stroke patients age 18-60 years old were selected using consecutive sampling technique. This study was conducted on patients during their follow up in the outpatient department of unit neurology, Margono Soekardjo Purwokerto Hospital during November-December 2015. The characteristics of the recurrent stroke patients include sex, age, education, occupation, and income. This study also describes type of stroke and duration of illness. The periods of recurrent stroke patients divided in to three time periods (≤ 6-month, 7-12 month, >12 month). Results: 73 recurrent stroke patients showed 56% were female, age group 39-60 years old was 97,5%, 60,3% have low education (below senior high school), 64,7% work as public and private employees. Income of respondents were low income 53,4%. Ischemic stroke was the majority (87,7%), no history family of stroke 64,4%, 1-5 years duration of illness and periods of stroke recurrence >12 month was 45,20%.Conclusion:  Ischemic stroke is the biggest case of recurrent stroke, so that we need to emphasize the importance of secondary prevention including medication and treatment.

scholarly journals Impact of excessive supraventricular ectopic activity detected in the acute phase of stroke or TIA on AF detection and death within 24 months – results of the prospective MonDAFIS study

2021 ◽  
Vol 42 (Supplement_1) ◽  
Author(s):  
K G H Haeusler ◽  
M C O Olma ◽  
S T Tuetuencue ◽  
C F Fiessler ◽  
C K Kunze ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Atrial Fibrillation ◽  
Ischemic Stroke ◽  
Acute Ischemic Stroke ◽  
Major Bleeding ◽  
Recurrent Stroke ◽  
First Episode ◽  
Ecg Monitoring ◽  
Ectopic Activity ◽  
Stroke Patients

Abstract Background/Introduction Detection of atrial fibrillation (AF) and subsequent initiation of oral anticoagulation remain key goals in the care of stroke patients. The European Society of Cardiology guideline recommend continuous ECG monitoring for at least 72 hours in stroke patients without previously known AF. Excessive supraventricular ectopic activity (ESVEA) has been identified as a marker for patients at risk for AF in the general population. Robust data on the clinical relevance of ESVEA detected in the acute phase of ischemic stroke or transient ischemic attack (TIA) are lacking. Purpose To assess the impact of ESVEA (defined as presence of supraventricular beats ≥480/day or at least one atrial run of ≥10 and &lt;30 seconds during continuous ECG monitoring for 72 hours) in patients with acute ischemic stroke/TIA without (previously) known AF on recurrent stroke, all-cause death and detection of a first episode of AF within 24 months. Methods The investigator-initiated, prospective, open, multicenter Systematic Monitoring for Detection of Atrial Fibrillation in Patients with Acute Ischemic Stroke study randomized 3,465 acute stroke patients without known AF 1:1 to usual diagnostic procedures for AF detection or additive Holter-ECG recording for up to seven days in-hospital (NCT02869386). ECG core-lab analysis included the number of atrial ectopic beats per day, the number of atrial runs as well as the duration of the longest atrial run per 24 hours. Patients were followed-up for two years. Secondary study objectives include the comparison of recurrent stroke, myocardial infarction, major bleeding and all-cause death in ESVEA patients, patients with newly diagnosed AF vs. non-ESVEA patients with sinus rhythm at baseline. Data were analyzed using Fisher's exact test. Results In 1,714 patients randomized to the intervention group, 1,693 (98.8%) had analyzable ECG recordings of a median duration of 121 hours (IQR 73–166). 1,435 (84.8%) patients had continuous ECG monitoring for the first 72 hours. At this time, ESVEA was detected in 363 (25.3%) of 1,435 patients, while a first episode of AF was detected in 48 (3.3%). At 24 months, AF was newly detected in 57 (15.7%) ESVEA patients vs. 53 (6.2%) non-ESVEA patients (p&lt;0.001) with available follow-up. At 24 months, 68 (24.5%) ESVEA patients vs. 77 (9.0%) non-ESVEA patients were on oral anticoagulation (p&lt;0.001). The composite of recurrent stroke, myocardial infarction, major bleeding and death at 24 months did not differ significantly between ESVEA patients vs. non-ESVEA patients (14.3% vs. 11.6%; p=0.389). However, all-cause death was higher in ESVEA patients (6.6% vs. 3.1% in non-ESVEA patients; p=0.01). Conclusions ESVEA detected after acute ischemic stroke/TIA identifies patients at high-risk for AF and may be used to guide prolonged ECG monitoring. The higher risk of death in ESVEA patients vs. non-ESVEA patients within 24 months after stroke/TIA deserves further investigation. FUNDunding Acknowledgement Type of funding sources: Private company. Main funding source(s): Bayer Vital GmbH, Bayer HealthCare Pharmaceuticals, Germany.

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