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2. Early Assessment of the Added Value of FDG-PET/CT and MRI-DWI in Monitoring Treatment Response of Stage III Non-Small Cell Lung Cancer

Author

Siegersma, Klaske R., Hummel, J. Marjan, Broekhuizen, Henk, de Geus-Oei, Lioe-Fee, Magjarevic, Ratko, Editor-in-chief, Ładyżyński, Piotr, Series editor, Ibrahim, Fatimah, Series editor, Lacković, Igor, Series editor, Rock, Emilio Sacristan, Series editor, Kyriacou, Efthyvoulos, editor, Christofides, Stelios, editor, and Pattichis, Constantinos S., editor

Published
2016
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3. Coronary calcification measures predict mortality in symptomatic women and men

Author

Siegersma, Klaske R, primary, Groepenhoff, Floor, additional, Eikendal, Anouk L M, additional, op den Brouw, Willemijn J, additional, Leiner, Tim, additional, Appelman, Yolande, additional, Tulevski, Igor I, additional, Somsen, G Aernout, additional, Onland-Moret, N Charlotte, additional, Hofstra, Leonard, additional, and den Ruijter, Hester M, additional

Published
2022
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4. Sex Differences in the Relationship between New York Heart Association Functional Classification and Survival in Cardiovascular Disease Patients

Author

Siegersma, Klaske R., Stens, Niels A., Groepenhoff, Floor, Appelman, Yolande, Tulevski, Igor I., Hofstra, Leonard, den Ruijter, Hester M., Somsen, G. Aernout, Onland-Moret, N. Charlotte, Cardiology, ACS - Atherosclerosis & ischemic syndromes, ACS - Microcirculation, and ACS - Heart failure & arrhythmias

Subjects
All institutes and research themes of the Radboud University Medical Center, Vascular damage Radboud Institute for Health Sciences [Radboudumc 16], General Medicine, Cardiology and Cardiovascular Medicine
Abstract

Background: The New York Heart Association (NYHA) functional class has extensively been used for risk stratification in patients suspected of heart failure, although its prognostic value differs between sexes and disease entities. Functional exercise capacity might explain the association between NYHA functional class and survival, and can serve as an objective proxy for the subjective nature of the NYHA classification. Therefore, we assessed whether sex-differences in exercise capacity explain the association between NYHA functional class and survival in patients suspected of cardiovascular disease. Methods: Electronic health record data from 7259 patients with cardiovascular symptoms, a documented NYHA functional class and cardiac stress electrocardiogram (ECG), was analysed. Followup for all-cause mortality was obtained through linkage with Statistics Netherlands. A sex-stratified mediation analysis was performed to assess to what extent the proportional heart rate and -workload during ECG stress testing explain the association between NYHA functional class and survival. Results: In men, increments in NYHA functional class were related to higher all-cause mortality in a dose-response manner (NYHA II vs III/IV: hazard ratio [HR] 1.59 vs 3.64, referenced to NYHA I), whilst in women those classified as NYHA functional class II and III/IV had a similar higher mortality risk (HR 1.49 vs 1.41). Sex-stratified mediation analysis showed that the association between NYHA and survival was mostly explained by proportional workload during stress ECG (men vs women: 22.9%, 95% CI: 18.9%–27.3% vs 40.3%, 95% CI: 28.5%–68.6%) and less so by proportional heart rate (men vs women: 2.5%, 95% CI: 1.3%–4.3% vs 8.0%, 95% CI: 4.1%–18.1%). Post-hoc analysis showed that NYHA classification explained a minor proportion of the association between proportional workload and all-cause mortality (men vs women: 15.1%, 95% CI: 12.0%–18.3% vs 4.4%, 95% CI: 1.5%–7.4%). Conclusions: This study showed a significant mediation in both sexes on the association between NYHA functional class and all-cause mortality by proportional workload, but the effect explained by NYHA classification on the association between survival and proportional workload is small. This implies that NYHA classification is not a sole representation of a patient’s functional capacity, but might also incude other aspects of the patient’s overall health status.

Published
2022

5. Development of a Pipeline for Adverse Drug Reaction Identification in Clinical Notes: Word Embedding Models and String Matching

Author

Siegersma, Klaske R., Evers, Maxime, Bots, Sophie H, Groepenhoff, Floor, Appelman, Yolande, Hofstra, Leonard, Tulevski, Igor I, Somsen, G Aernout, den Ruijter, Hester M, Spruit, Marco, Onland-Moret, N Charlotte, Siegersma, Klaske R., Evers, Maxime, Bots, Sophie H, Groepenhoff, Floor, Appelman, Yolande, Hofstra, Leonard, Tulevski, Igor I, Somsen, G Aernout, den Ruijter, Hester M, Spruit, Marco, and Onland-Moret, N Charlotte

Abstract

BACKGROUND: Knowledge about adverse drug reactions (ADRs) in the population is limited because of underreporting, which hampers surveillance and assessment of drug safety. Therefore, gathering accurate information that can be retrieved from clinical notes about the incidence of ADRs is of great relevance. However, manual labeling of these notes is time-consuming, and automatization can improve the use of free-text clinical notes for the identification of ADRs. Furthermore, tools for language processing in languages other than English are not widely available.OBJECTIVE: The aim of this study is to design and evaluate a method for automatic extraction of medication and Adverse Drug Reaction Identification in Clinical Notes (ADRIN).METHODS: Dutch free-text clinical notes (N=277,398) and medication registrations (N=499,435) from the Cardiology Centers of the Netherlands database were used. All clinical notes were used to develop word embedding models. Vector representations of word embedding models and string matching with a medical dictionary (Medical Dictionary for Regulatory Activities [MedDRA]) were used for identification of ADRs and medication in a test set of clinical notes that were manually labeled. Several settings, including search area and punctuation, could be adjusted in the prototype to evaluate the optimal version of the prototype.RESULTS: The ADRIN method was evaluated using a test set of 988 clinical notes written on the stop date of a drug. Multiple versions of the prototype were evaluated for a variety of tasks. Binary classification of ADR presence achieved the highest accuracy of 0.84. Reduced search area and inclusion of punctuation improved performance, whereas incorporation of the MedDRA did not improve the performance of the pipeline.CONCLUSIONS: The ADRIN method and prototype are effective in recognizing ADRs in Dutch clinical notes from cardiac diagnostic screening centers. Surprisingly, incorporation of the Med

Published
2022

6. Coronary calcification measures predict mortality in symptomatic women and men

Author

Cardiologie, Experimental Cardiology Laboratory, Experimentele Afd. Cardiologie 1, CDL Poli WKZ, CDL Onderzoek Pasterkamp, Onderzoek Vrouw Hart & Vaatziekten, Circulatory Health, MS Radiologie, Hart- en Vaatziekten Team A, JC onderzoeksprogramma Cardiovasculaire Epidemiologie, Cardiovasculaire Epi Team 3, Siegersma, Klaske R., Groepenhoff, Floor, Eikendal, Anouk L.M., Op Den Brouw, Willemijn J., Leiner, Tim, Appelman, Yolande, Tulevski, Igor I., Somsen, G. Aernout, Onland-Moret, N. Charlotte, Hofstra, Leonard, Den Ruijter, Hester M., Cardiologie, Experimental Cardiology Laboratory, Experimentele Afd. Cardiologie 1, CDL Poli WKZ, CDL Onderzoek Pasterkamp, Onderzoek Vrouw Hart & Vaatziekten, Circulatory Health, MS Radiologie, Hart- en Vaatziekten Team A, JC onderzoeksprogramma Cardiovasculaire Epidemiologie, Cardiovasculaire Epi Team 3, Siegersma, Klaske R., Groepenhoff, Floor, Eikendal, Anouk L.M., Op Den Brouw, Willemijn J., Leiner, Tim, Appelman, Yolande, Tulevski, Igor I., Somsen, G. Aernout, Onland-Moret, N. Charlotte, Hofstra, Leonard, and Den Ruijter, Hester M.

Published
2022

7. Development of a Pipeline for Adverse Drug Reaction Identification in Clinical Notes: Word Embedding Models and String Matching

Author

Afd Pharmacoepi & Clinical Pharmacology, Pharmacoepidemiology and Clinical Pharmacology, Siegersma, Klaske R., Evers, Maxime, Bots, Sophie H, Groepenhoff, Floor, Appelman, Yolande, Hofstra, Leonard, Tulevski, Igor I, Somsen, G Aernout, den Ruijter, Hester M, Spruit, Marco, Onland-Moret, N Charlotte, Afd Pharmacoepi & Clinical Pharmacology, Pharmacoepidemiology and Clinical Pharmacology, Siegersma, Klaske R., Evers, Maxime, Bots, Sophie H, Groepenhoff, Floor, Appelman, Yolande, Hofstra, Leonard, Tulevski, Igor I, Somsen, G Aernout, den Ruijter, Hester M, Spruit, Marco, and Onland-Moret, N Charlotte

Published
2022

8. Sex Differences in the Relationship between New York Heart Association Functional Classification and Survival in Cardiovascular Disease Patients: A Mediation Analysis of Exercise Capacity with Regular Care Data

Author

Siegersma, Klaske R., Stens, N.A., Groepenhoff, Floor, Appelman, Yolande, Tulevski, Igor I., Hofstra, Leonard, Aernout Somsen, G., Charlotte Onland-Moret, N., Siegersma, Klaske R., Stens, N.A., Groepenhoff, Floor, Appelman, Yolande, Tulevski, Igor I., Hofstra, Leonard, Aernout Somsen, G., and Charlotte Onland-Moret, N.

Abstract

Contains fulltext : 285293.pdf (Publisher’s version ) (Open Access)

Published
2022

9. Deep neural networks reveal novel sex-specific electrocardiographic features relevant for mortality risk

Author

Cardiovasculaire Immunologie, Experimental Cardiology Laboratory, Experimentele Afd. Cardiologie 1, Team Onderzoek, Cardiovasculaire Epi Team 3, Circulatory Health, JC onderzoeksprogramma Cardiovascular Health, Cardiovasculaire Epi Team 5, Cardiovasculaire Epidemiologie, Gezonde Vaten, Team Medisch, Regenerative Medicine and Stem Cells, Onderzoek Vrouw Hart & Vaatziekten, Siegersma, Klaske R., Van De Leur, Rutger R., Onland-Moret, N. Charlotte, Leon, David A., Diez-Benavente, Ernest, Rozendaal, Liesbeth, Bots, Michiel L., Coronel, Ruben, Appelman, Yolande, Hofstra, Leonard, Van Der Harst, Pim, Doevendans, Pieter A., Hassink, Rutger J., Den Ruijter, Hester M., Van Es, Rene, Cardiovasculaire Immunologie, Experimental Cardiology Laboratory, Experimentele Afd. Cardiologie 1, Team Onderzoek, Cardiovasculaire Epi Team 3, Circulatory Health, JC onderzoeksprogramma Cardiovascular Health, Cardiovasculaire Epi Team 5, Cardiovasculaire Epidemiologie, Gezonde Vaten, Team Medisch, Regenerative Medicine and Stem Cells, Onderzoek Vrouw Hart & Vaatziekten, Siegersma, Klaske R., Van De Leur, Rutger R., Onland-Moret, N. Charlotte, Leon, David A., Diez-Benavente, Ernest, Rozendaal, Liesbeth, Bots, Michiel L., Coronel, Ruben, Appelman, Yolande, Hofstra, Leonard, Van Der Harst, Pim, Doevendans, Pieter A., Hassink, Rutger J., Den Ruijter, Hester M., and Van Es, Rene

Published
2022

10. Outcomes in patients with a first episode of chest pain undergoing early coronary CT imaging

Author

Experimentele Afd. Cardiologie 1, Cardiovasculaire Epi Team 3, Circulatory Health, JC onderzoeksprogramma Cardiovasculaire Epidemiologie, Team Medisch, Onderzoek Vrouw Hart & Vaatziekten, Siegersma, Klaske R, Onland-Moret, N Charlotte, Appelman, Yolande, van der Harst, Pim, Tulevski, Igor I, Somsen, G Aernout, Narula, Jagat, den Ruijter, Hester M, Hofstra, Leonard, Experimentele Afd. Cardiologie 1, Cardiovasculaire Epi Team 3, Circulatory Health, JC onderzoeksprogramma Cardiovasculaire Epidemiologie, Team Medisch, Onderzoek Vrouw Hart & Vaatziekten, Siegersma, Klaske R, Onland-Moret, N Charlotte, Appelman, Yolande, van der Harst, Pim, Tulevski, Igor I, Somsen, G Aernout, Narula, Jagat, den Ruijter, Hester M, and Hofstra, Leonard

Published
2022

11. Deep neural networks reveal novel sex-specific electrocardiographic features relevant for mortality risk

Author

Siegersma, Klaske R, primary, van de Leur, Rutger R, additional, Onland-Moret, N Charlotte, additional, Leon, David A, additional, Diez-Benavente, Ernest, additional, Rozendaal, Liesbeth, additional, Bots, Michiel L, additional, Coronel, Ruben, additional, Appelman, Yolande, additional, Hofstra, Leonard, additional, van der Harst, Pim, additional, Doevendans, Pieter A, additional, Hassink, Rutger J, additional, den Ruijter, Hester M, additional, and van Es, René, additional

Published
2022
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13. Development of a Pipeline for Adverse Drug Reaction Identification in Clinical Notes: Word Embedding Models and String Matching

Author

Siegersma, Klaske R, primary, Evers, Maxime, additional, Bots, Sophie H, additional, Groepenhoff, Floor, additional, Appelman, Yolande, additional, Hofstra, Leonard, additional, Tulevski, Igor I, additional, Somsen, G Aernout, additional, den Ruijter, Hester M, additional, Spruit, Marco, additional, and Onland-Moret, N Charlotte, additional

Published
2022
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15. Outcomes in patients with a first episode of chest pain undergoing early coronary CT imaging.

Author

Siegersma, Klaske R., Onland-Moret, N. Charlotte, Appelman, Yolande, van der Harst, Pim, Tulevski, Igor I., Somsen, G. Aernout, Narula, Jagat, den Ruijter, Hester M., and Hofstra, Leonard

Subjects
CHEST pain diagnosis, PREDICTIVE tests, ANGINA pectoris, CORONARY angiography, CORONARY artery disease, CHEST pain, COMPUTED tomography, DISEASE complications
Abstract

Objectives: To investigate the impact of a CT-first strategy on all-cause and cardiovascular mortality in patients presenting with chest pain in outpatient cardiology clinics.Methods: Patients with a first presentation of suspected angina pectoris were identified and their data linked to the registrations of Statistics Netherlands for information on mortality. The linked database consisted of 33 068 patients. CT-first patients were defined as patients with a CT calcium score and coronary CT angiography, within 6 weeks after their initial visit. Propensity score matching (1:5) was used to match patients with and without a CT-first strategy. After matching, 12 545 patients were included of which 2308 CT-first patients and 10 237 patients that underwent usual care.Results: Mean age was 57 years, 56.3% were women and median follow-up was 4.9 years. All-cause mortality was significantly lower in CT-first patients (n=43, 1.9%) compared with patients without CT (n=363, 3.5%) (HR: 0.51, 95% CI 0.37 to 0.70). Furthermore, CT-first patients were more likely to receive cardiovascular preventative and antianginal medication (aspirin: 44.9% vs 27.1%, statins: 48.7% vs 30.3%, beta-blockers: 37.8% vs 25.5%, in CT-first and without CT-first patients, respectively) and to undergo downstream diagnostics and interventions (coronary interventions: 8.5% vs 5.7%, coronary angiography: 16.2% vs 10.6% in CT-first and without CT-first patients, respectively).Conclusions: In a real-world regular care database, a CT-first strategy in patients suspected of angina pectoris was associated with a lowering of all-cause mortality. [ABSTRACT FROM AUTHOR]

Published
2022
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16. Development of a Pipeline for Adverse Drug Reaction Identification in Clinical Notes: Word Embedding Models and String Matching (Preprint)

Author

Siegersma, Klaske R, primary, Evers, Maxime, additional, Bots, Sophie H, additional, Groepenhoff, Floor, additional, Appelman, Yolande, additional, Hofstra, Leonard, additional, Tulevski, Igor I, additional, Somsen, G Aernout, additional, den Ruijter, Hester M, additional, Spruit, Marco, additional, and Onland-Moret, N Charlotte, additional

Published
2021
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17. Additional file 1 of Routine clinical care data from thirteen cardiac outpatient clinics: design of the Cardiology Centers of the Netherlands (CCN) database

Author

Bots, Sophie H., Siegersma, Klaske R., Onland-Moret, N. Charlotte, Asselbergs, Folkert W., Somsen, G. Aernout, Tulevski, Igor I., den Ruijter, Hester M., and Hofstra, Leonard

Subjects
ComputingMethodologies_DOCUMENTANDTEXTPROCESSING, ComputingMilieux_COMPUTERSANDEDUCATION, Data_FILES, ComputerApplications_COMPUTERSINOTHERSYSTEMS
Abstract

Additional file 1. Supplementary figure and tables.

Published
2021
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18. Routine clinical care data from thirteen cardiac outpatient clinics: design of the Cardiology Centers of the Netherlands (CCN) database

Author

Onderzoek Vrouw Hart & Vaatziekten, Experimentele Afd. Cardiologie 1, Cardiovasculaire Epi Team 3, Circulatory Health, JC onderzoeksprogramma Cardiovasculaire Epidemiologie, Team Medisch, Bots, Sophie H, Siegersma, Klaske R, Onland-Moret, N Charlotte, Asselbergs, Folkert W, Somsen, G Aernout, Tulevski, Igor I, den Ruijter, Hester M, Hofstra, Leonard, Onderzoek Vrouw Hart & Vaatziekten, Experimentele Afd. Cardiologie 1, Cardiovasculaire Epi Team 3, Circulatory Health, JC onderzoeksprogramma Cardiovasculaire Epidemiologie, Team Medisch, Bots, Sophie H, Siegersma, Klaske R, Onland-Moret, N Charlotte, Asselbergs, Folkert W, Somsen, G Aernout, Tulevski, Igor I, den Ruijter, Hester M, and Hofstra, Leonard

Published
2021

19. New York Heart Association class is strongly associated with mortality beyond heart failure in symptomatic women

Author

Experimentele Afd. Cardiologie 1, CDL Onderzoek Pasterkamp, Cardiovasculaire Epi Team 3, Circulatory Health, JC onderzoeksprogramma Cardiovascular Health, Onderzoek Vrouw Hart & Vaatziekten, Siegersma, Klaske R, Groepenhoff, Floor, Onland-Moret, N Charlotte, Tulevski, Igor I, Hofstra, Leonard, Somsen, G Aernout, Den Ruijter, Hester M, Experimentele Afd. Cardiologie 1, CDL Onderzoek Pasterkamp, Cardiovasculaire Epi Team 3, Circulatory Health, JC onderzoeksprogramma Cardiovascular Health, Onderzoek Vrouw Hart & Vaatziekten, Siegersma, Klaske R, Groepenhoff, Floor, Onland-Moret, N Charlotte, Tulevski, Igor I, Hofstra, Leonard, Somsen, G Aernout, and Den Ruijter, Hester M

Published
2021

23. Deep neural networks reveal novel sex-specific electrocardiographic features relevant for mortality risk.

Author

Siegersma KR, van de Leur RR, Onland-Moret NC, Leon DA, Diez-Benavente E, Rozendaal L, Bots ML, Coronel R, Appelman Y, Hofstra L, van der Harst P, Doevendans PA, Hassink RJ, den Ruijter HM, and van Es R

Abstract

Aims: Incorporation of sex in study design can lead to discoveries in medical research. Deep neural networks (DNNs) accurately predict sex based on the electrocardiogram (ECG) and we hypothesized that misclassification of sex is an important predictor for mortality. Therefore, we first developed and validated a DNN that classified sex based on the ECG and investigated the outcome. Second, we studied ECG drivers of DNN-classified sex and mortality., Methods and Results: A DNN was trained to classify sex based on 131 673 normal ECGs. The algorithm was validated on internal (68 500 ECGs) and external data sets (3303 and 4457 ECGs). The survival of sex (mis)classified groups was investigated using time-to-event analysis and sex-stratified mediation analysis of ECG features. The DNN successfully distinguished female from male ECGs {internal validation: area under the curve (AUC) 0.96 [95% confidence interval (CI): 0.96, 0.97]; external validations: AUC 0.89 (95% CI: 0.88, 0.90), 0.94 (95% CI: 0.93, 0.94)}. Sex-misclassified individuals (11%) had a 1.4 times higher mortality risk compared with correctly classified peers. The ventricular rate was the strongest mediating ECG variable (41%, 95% CI: 31%, 56%) in males, while the maximum amplitude of the ST segment was strongest in females (18%, 95% CI: 11%, 39%). Short QRS duration was associated with higher mortality risk., Conclusion: Deep neural networks accurately classify sex based on ECGs. While the proportion of ECG-based sex misclassifications is low, it is an interesting biomarker. Investigation of the causal pathway between misclassification and mortality uncovered new ECG features that might be associated with mortality. Increased emphasis on sex as a biological variable in artificial intelligence is warranted., (© The Author(s) 2022. Published by Oxford University Press on behalf of European Society of Cardiology.)

Published
2022
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