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Article ; Online: Phase-2 Re-Entry in Brugada Syndrome: More to Understand Than "Just" I

Kanters, Jørgen K / Nielsen, Morten S

2023 Volume 9, Issue 12, Page(s) 2475–2476

MeSH term(s)	Humans ; Brugada Syndrome/diagnosis ; Mutation
Language	English
Publishing date	2023-12-27
Publishing country	United States
Document type	Editorial ; Comment
ZDB-ID	2846739-5
ISSN	2405-5018 ; 2405-500X ; 2405-500X
ISSN (online)	2405-5018 ; 2405-500X
ISSN	2405-500X
DOI	10.1016/j.jacep.2023.10.030
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Article ; Online: Effect of hyperglycaemia in combination with moxifloxacin on cardiac repolarization in male and female patients with type I diabetes.

Taubel, Jorg / Pimenta, Dominic / Cole, Samuel Thomas / Graff, Claus / Kanters, Jørgen K / Camm, A John

Clinical research in cardiology : official journal of the German Cardiac Society

2022 Volume 111, Issue 10, Page(s) 1147–1160

Abstract: Background: Patients with Type 1 diabetes mellitus have been shown to be at a two to ten-fold higher risk of sudden cardiac death (SCD) (Svane et al., Curr Cardiol 2020; 22:112) than the general population, but the underlying mechanism is unclear. ... ...

Abstract	Background: Patients with Type 1 diabetes mellitus have been shown to be at a two to ten-fold higher risk of sudden cardiac death (SCD) (Svane et al., Curr Cardiol 2020; 22:112) than the general population, but the underlying mechanism is unclear. Hyperglycaemia is a recognised cause of QTc prolongation; a state patients with type 1 diabetes are more prone to, potentially increasing their risk of ventricular arrhythmia. Understanding the QTc prolongation effect of both hyperglycaemia and the concomitant additive risk of commonly prescribed QTc-prolonging drugs such as Moxifloxacin may help to elucidate the mechanism of sudden cardiac death in this cohort. This single-blinded, placebo-controlled study investigated the extent to which hyperglycaemia prolongs the QTc in controlled conditions, and the potential additive risk of QTc-prolonging medications. Methods: 21 patients with type 1 diabetes mellitus were enrolled to a placebo-controlled crossover study at a single clinical trials unit. Patients underwent thorough QTc assessment throughout the study. A 'hyperglycaemic clamp' of oral and intravenous glucose was administered with a target blood glucose of > 25 mM and maintained for 2 h on day 1 and day 3, alongside placebo on day 1 and moxifloxacin on day 3. Day 2 served as a control day between the two active treatment days. Thorough QTc assessment was conducted at matched time points over 3 days, and regular blood sampling was undertaken at matched time intervals for glucose levels and moxifloxacin exposure. Results: Concentration-effect modelling showed that acute hyperglycaemia prolonged the QTc interval in female and male volunteers with type 1 diabetes by a peak mean increase of 13 ms at 2 h. Peak mean QTc intervals after the administration of intravenous Moxifloxacin during the hyperglycaemic state were increased by a further 9 ms at 2 h, to 22 ms across the entire study population. Regression analysis suggested this additional increase was additive, not exponential. Hyperglycaemia was associated with a significantly greater mean QTc-prolonging effect in females, but the mean peak increase with the addition of moxifloxacin was the same for males and females. This apparent sex difference was likely due to the exclusive use of basal insulin in the male patients, which provided a low level of exogenous insulin during the study assessments thereby mitigating the effects of hyperglycaemia on QTc. This effect was partially overcome by Moxifloxacin administration, suggesting both hyperglycaemia and moxifloxacin prolong QTc by different mechanisms, based on subinterval analysis. Conclusions: Hyperglycaemia was found to be a significant cause of QTc prolongation and the additional effect of a QTc-prolonging positive control (moxifloxacin) was found to be additive. Given the high risk of sudden cardiac death in type 1 diabetes mellitus, extra caution should be exercised when prescribing any medication in this cohort for QTc effects, and further research needs to be undertaken to elucidate the exact mechanism underlying this finding and explore the potential prescribing risk in diabetes. Trial registration: NCT number: NCT01984827.
MeSH term(s)	Blood Glucose ; Cross-Over Studies ; Death, Sudden, Cardiac ; Diabetes Mellitus, Type 1/complications ; Diabetes Mellitus, Type 1/drug therapy ; Double-Blind Method ; Female ; Heart Rate ; Humans ; Hyperglycemia/complications ; Hyperglycemia/drug therapy ; Insulins/pharmacology ; Long QT Syndrome ; Male ; Moxifloxacin/adverse effects
Chemical Substances	Blood Glucose ; Insulins ; Moxifloxacin (U188XYD42P)
Language	English
Publishing date	2022-05-21
Publishing country	Germany
Document type	Journal Article ; Randomized Controlled Trial
ZDB-ID	2213295-8
ISSN	1861-0692 ; 1861-0684
ISSN (online)	1861-0692
ISSN	1861-0684
DOI	10.1007/s00392-022-02037-8
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Article ; Online: Electrocardiographic markers in patients with type 2 diabetes and the role of diabetes duration.

Isaksen, Jonas L / Sivertsen, Christian B / Jensen, Christian Zinck / Graff, Claus / Linz, Dominik / Ellervik, Christina / Jensen, Magnus T / Jørgensen, Peter G / Kanters, Jørgen K

Journal of electrocardiology

2024 Volume 84, Page(s) 129–136

Abstract: Background: The association between type 2 diabetes and electrocardiographic (ECG) markers are incompletely explored and the dependence on diabetes duration is largely unknown. We aimed to investigate the electrocardiographic (ECG) changes associated ... ...

Abstract	Background: The association between type 2 diabetes and electrocardiographic (ECG) markers are incompletely explored and the dependence on diabetes duration is largely unknown. We aimed to investigate the electrocardiographic (ECG) changes associated with type 2 diabetes over time. Methods: In this cross-sectional study, we matched people with type 2 diabetes 1:1 on sex, age, and body mass index with people without diabetes from the general population. We regressed ECG markers with the presence of diabetes and the duration of clinical diabetes, respectively, adjusted for sex, age, body mass index, smoking, heart rate, diabetes medication, renal function, hypertension, and myocardial infarction. Results: We matched 988 people with type 2 diabetes (332, 34% females) with as many controls. Heart rate was 8 bpm higher (p < 0.001) in people with vs. without type 2 diabetes, but the difference declined with increasing diabetes duration. For most depolarization markers, the difference between people with and without type 2 diabetes increased progressively with diabetes duration. On average, R-wave amplitude was 6 mm lower in lead V5 (p < 0.001), P-wave duration was 5 ms shorter (p < 0.001) and QRS duration was 3 ms (p = 0.03). Among repolarization markers, T-wave amplitude (measured in V5) was lower in patients with type 2 diabetes (1 mm lower, p < 0.001) and the QRS-T angle was 10 degrees wider (p = 0.002). We observed no association between diabetes duration and repolarization markers. Conclusions: Type 2 diabetes was independently associated with electrocardiographic depolarization and repolarization changes. Differences in depolarization markers, but not repolarization markers, increased with increasing diabetes duration.
Language	English
Publishing date	2024-04-20
Publishing country	United States
Document type	Journal Article
ZDB-ID	410286-1
ISSN	1532-8430 ; 0022-0736
ISSN (online)	1532-8430
ISSN	0022-0736
DOI	10.1016/j.jelectrocard.2024.04.003
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Article ; Online: Frequency of Long QT in Patients with SARS-CoV-2 Infection Treated with Hydroxychloroquine: A Meta-analysis.

Oscanoa, Teodoro J / Vidal, Xavier / Kanters, Jørgen K / Romero-Ortuno, Roman

International journal of antimicrobial agents

2020 Volume 56, Issue 6, Page(s) 106212

Abstract: Introduction Hydroxychloroquine (HCQ) has been proposed as a SARS-CoV-2 treatment but the frequency of long QT (LQT) during use is unknown. Objective To conduct a meta-analysis of the frequency of LQT in patients with SARS-CoV-2 infection treated with ... ...

Abstract	Introduction Hydroxychloroquine (HCQ) has been proposed as a SARS-CoV-2 treatment but the frequency of long QT (LQT) during use is unknown. Objective To conduct a meta-analysis of the frequency of LQT in patients with SARS-CoV-2 infection treated with HCQ. Data Sources PubMed, EMBASE, Google Scholar, the Cochrane Database of Systematic Reviews and preprint servers (medRxiv, Research Square) were searched for studies published between December 2019 and June 30, 2020. Methods Effect statistics were pooled using random effects. The quality of observational studies and randomized controlled trials was appraised with STROBE and the Cochrane Risk of Bias Assessment tools, respectively. Outcomes Critical LQT was defined as: (1) maximum QT corrected (QTc)≥500 ms (if QRS<120 ms) or QTc≥550 ms (if QRS≥120 ms), and (2) QTc increase ≥60 ms. Results In the 28 studies included (n=9124), the frequency of LQT during HCQ treatment was 6.7% (95% confidence interval [CI]: 3.7-10.2). In 20 studies (n=7825), patients were also taking other QT-prolonging drugs. The frequency of LQT in the other 8 studies (n=1299) was 1.7% (95% CI: 0.3-3.9). Twenty studies (n=6869) reported HCQ discontinuation due to LQT, with a frequency of 3.7% (95% CI: 1.5-6.6). The frequency of ventricular arrhythmias during HCQ treatment was 1.68% (127/7539) and that of arrhythmogenic death was 0.69% (39/5648). Torsades de Pointes occurred in 0.06% (3/5066). Patients aged >60 years were at highest risk of HCQ-associated LQT (P<0.001). Conclusions HCQ-associated cardiotoxicity in SARS-CoV-2 patients is uncommon but requires ECG monitoring, particularly in those aged >60 years and/or taking other QT-prolonging drugs.
MeSH term(s)	Aged ; COVID-19/drug therapy ; Electrocardiography/drug effects ; Female ; Humans ; Hydroxychloroquine/adverse effects ; Long QT Syndrome/chemically induced ; Male ; Middle Aged ; SARS-CoV-2
Chemical Substances	Hydroxychloroquine (4QWG6N8QKH)
Keywords	covid19
Language	English
Publishing date	2020-10-24
Publishing country	Netherlands
Document type	Journal Article ; Meta-Analysis
ZDB-ID	1093977-5
ISSN	1872-7913 ; 0924-8579
ISSN (online)	1872-7913
ISSN	0924-8579
DOI	10.1016/j.ijantimicag.2020.106212
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Article ; Online: Celebrities in the heart, strangers in the pancreatic beta cell: Voltage-gated potassium channels K

Lubberding, Anniek F / Juhl, Christian R / Skovhøj, Emil Z / Kanters, Jørgen K / Mandrup-Poulsen, Thomas / Torekov, Signe S

Acta physiologica (Oxford, England)

2022 Volume 234, Issue 3, Page(s) e13781

Abstract: Voltage-gated potassium ( ... ...

Abstract	Voltage-gated potassium (K
MeSH term(s)	Diabetes Mellitus, Type 2/genetics ; ERG1 Potassium Channel/genetics ; Genome-Wide Association Study ; Humans ; Hyperinsulinism/genetics ; Hypoglycemia/genetics ; Insulin-Secreting Cells/metabolism ; KCNQ1 Potassium Channel/genetics ; KCNQ1 Potassium Channel/metabolism ; Long QT Syndrome/genetics ; Long QT Syndrome/metabolism ; Mutation
Chemical Substances	ERG1 Potassium Channel ; KCNH2 protein, human ; KCNQ1 Potassium Channel ; KCNQ1 protein, human
Language	English
Publishing date	2022-01-22
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	2218636-0
ISSN	1748-1716 ; 1748-1708
ISSN (online)	1748-1716
ISSN	1748-1708
DOI	10.1111/apha.13781
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Article: Frequency of Long QT in Patients with SARS-CoV-2 Infection Treated with Hydroxychloroquine: A Meta-analysis

Oscanoa, Teodoro J / Vidal, Xavier / Kanters, Jørgen K / Romero-Ortuno, Roman

International journal of antimicrobial agents. 2020 Dec., v. 56, no. 6

2020

Abstract: Introduction Hydroxychloroquine (HCQ) has been proposed as a SARS-CoV-2 treatment but the frequency of long QT (LQT) during use is unknown.Objective To conduct a meta-analysis of the frequency of LQT in patients with SARS-CoV-2 infection treated with HCQ. ...

Abstract	Introduction Hydroxychloroquine (HCQ) has been proposed as a SARS-CoV-2 treatment but the frequency of long QT (LQT) during use is unknown.Objective To conduct a meta-analysis of the frequency of LQT in patients with SARS-CoV-2 infection treated with HCQ.Data Sources PubMed, EMBASE, Google Scholar, the Cochrane Database of Systematic Reviews and preprint servers (medRxiv, Research Square) were searched for studies published between December 2019 and June 30, 2020.Methods Effect statistics were pooled using random effects. The quality of observational studies and randomized controlled trials was appraised with STROBE and the Cochrane Risk of Bias Assessment tools, respectively.Outcomes Critical LQT was defined as: (1) maximum QT corrected (QTc)≥500 ms (if QRS<120 ms) or QTc≥550 ms (if QRS≥120 ms), and (2) QTc increase ≥60 ms.Results In the 28 studies included (n=9124), the frequency of LQT during HCQ treatment was 6.7% (95% confidence interval [CI]: 3.7-10.2). In 20 studies (n=7825), patients were also taking other QT-prolonging drugs. The frequency of LQT in the other 8 studies (n=1299) was 1.7% (95% CI: 0.3-3.9). Twenty studies (n=6869) reported HCQ discontinuation due to LQT, with a frequency of 3.7% (95% CI: 1.5-6.6). The frequency of ventricular arrhythmias during HCQ treatment was 1.68% (127/7539) and that of arrhythmogenic death was 0.69% (39/5648). Torsades de Pointes occurred in 0.06% (3/5066). Patients aged >60 years were at highest risk of HCQ-associated LQT (P<0.001).Conclusions HCQ-associated cardiotoxicity in SARS-CoV-2 patients is uncommon but requires ECG monitoring, particularly in those aged >60 years and/or taking other QT-prolonging drugs.
Keywords	anti-infective agents ; arrhythmia ; bias ; cardiotoxicity ; confidence interval ; databases ; death ; frequency ; infection ; meta-analysis ; monitoring ; observational studies ; patients ; research ; risk ; systematic review
Language	English
Dates of publication	2020-12
Publishing place	Elsevier Ltd
Document type	Article
Note	NAL-light
ZDB-ID	1093977-5
ISSN	1872-7913 ; 0924-8579
ISSN (online)	1872-7913
ISSN	0924-8579
DOI	10.1016/j.ijantimicag.2020.106212
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Article ; Online: Electrocardiography in euthyroid individuals: a Danish general population study.

Isaksen, Jonas L / Skov, Morten W / Graff, Claus / Ellervik, Christina / Kanters, Jørgen K

Minerva endocrinology

2020 Volume 47, Issue 1, Page(s) 103–110

Abstract: Background: Thyroid hormones within the euthyroid range have been linked to mortality and differences in heart rate. However, some relations between thyroid hormone concentration and various electrocardiographic measurements remain unassessed. We aimed ... ...

Abstract	Background: Thyroid hormones within the euthyroid range have been linked to mortality and differences in heart rate. However, some relations between thyroid hormone concentration and various electrocardiographic measurements remain unassessed. We aimed to investigate the association between thyroid hormone concentrations within the euthyroid range and different electrocardiographic markers in people free of thyroid disease. Methods: We obtained electrocardiograms (ECG) and blood samples of free T4, total T3, and thyrotropin (TSH) in 20,852 subjects from the general population (the GESUS study). Relations between concentrations of TSH, free T4, and total T3 and heart rate, QTc, QRS duration, PR interval, P-wave duration and T-wave morphology were assessed in a multivariate adjusted linear model stratified by sex. Results: Roughly half of the 18,046 included participants with thyroid hormone measurements within euthyroid range were men, and the average age was 56 years. Heart rate increased with concentrations of T3 (6.4 bpm/nM, P<0.001 in women and 5.3 bpm/nM, P<0.001 in men) and T4 (3.7 bpm/10pM, P<0.001 in women and 3.1 bpm/10pM, P<0.001 in men). We found no relation between TSH and heart rate. PR interval and QRS duration decreased with higher concentrations of T3 (all P<0.01). QTc increased with higher concentrations of T4 in men (5 ms/10pM), and T waves were flatter, more asymmetric, and more often had notches with higher concentrations of T4 (all P≤0.01). Conclusions: Thyroid hormone concentrations within the euthyroid range in people free of thyroid disease were associated with changes in the electrocardiogram in a general population.
MeSH term(s)	Denmark/epidemiology ; Electrocardiography ; Female ; Humans ; Male ; Middle Aged ; Thyroid Diseases/diagnosis ; Thyroid Hormones ; Thyrotropin ; Thyroxine ; Triiodothyronine
Chemical Substances	Thyroid Hormones ; Triiodothyronine (06LU7C9H1V) ; Thyrotropin (9002-71-5) ; Thyroxine (Q51BO43MG4)
Language	English
Publishing date	2020-07-23
Publishing country	Italy
Document type	Journal Article
ZDB-ID	3062786-2
ISSN	2724-6116
ISSN (online)	2724-6116
DOI	10.23736/S2724-6507.20.03170-3
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Article: First-Trimester Maternal Serum Adiponectin/Leptin Ratio in Pre-Eclampsia and Fetal Growth.

de Knegt, Victoria E / Hedley, Paula L / Eltvedt, Anna K / Placing, Sophie / Wøjdemann, Karen / Shalmi, Anne-Cathrine / Rode, Line / Kanters, Jørgen K / Sundberg, Karin / Tabor, Ann / Lausten-Thomsen, Ulrik / Christiansen, Michael

Life (Basel, Switzerland)

2023 Volume 13, Issue 1

Abstract: The serum adiponectin/leptin ratio (A/L ratio) is a surrogate marker of insulin sensitivity. Pre-eclampsia (PE) is associated with maternal metabolic syndrome and occasionally impaired fetal growth. We assessed whether the A/L ratio in first-trimester ... ...

Abstract	The serum adiponectin/leptin ratio (A/L ratio) is a surrogate marker of insulin sensitivity. Pre-eclampsia (PE) is associated with maternal metabolic syndrome and occasionally impaired fetal growth. We assessed whether the A/L ratio in first-trimester maternal serum was associated with PE and/or birth weight. Adiponectin and leptin were quantitated in first-trimester blood samples (gestational week 10+3−13+6) from 126 women who later developed PE with proteinuria (98 mild PE; 21 severe PE; 7 HELLP syndrome), and 297 controls, recruited from the Copenhagen First-Trimester Screening Study. The A/L ratio was reduced in PE pregnancies, median 0.17 (IQR: 0.12−0.27) compared with controls, median 0.32 (IQR: 0.19−0.62) (p < 0.001). A multiple logistic regression showed that PE was negatively associated with log A/L ratio independent of maternal BMI (odds ratio = 0.315, 95% CI = 0.191 to 0.519). Adiponectin (AUC = 0.632) and PAPP-A (AUC = 0.605) were negatively associated with PE, and leptin (AUC = 0.712) was positively associated with PE. However, the A/L ratio was a better predictor of PE (AUC = 0.737), albeit not clinically relevant as a single marker. No significant association was found between A/L ratio and clinical severity of pre-eclampsia or preterm birth. PE was associated with a significantly lower relative birth weight (p < 0.001). A significant negative correlation was found between relative birth weight and A/L ratio in controls (β = −0.165, p < 0.05) but not in PE pregnancies), independent of maternal BMI. After correction for maternal BMI, leptin was significantly associated with relative birth weight (β = 2.98, p < 0.05), while adiponectin was not significantly associated. Our findings suggest that an impairment of the A/L ratio (as seen in metabolic syndrome) in the first trimester is characteristic of PE, while aberrant fetal growth in PE is not dependent on insulin sensitivity, but rather on leptin-associated pathways.
Language	English
Publishing date	2023-01-03
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2662250-6
ISSN	2075-1729
ISSN	2075-1729
DOI	10.3390/life13010130
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Article ; Online: PTB-XL+, a comprehensive electrocardiographic feature dataset.

Strodthoff, Nils / Mehari, Temesgen / Nagel, Claudia / Aston, Philip J / Sundar, Ashish / Graff, Claus / Kanters, Jørgen K / Haverkamp, Wilhelm / Dössel, Olaf / Loewe, Axel / Bär, Markus / Schaeffter, Tobias

Scientific data

2023 Volume 10, Issue 1, Page(s) 279

Abstract: Machine learning (ML) methods for the analysis of electrocardiography (ECG) data are gaining importance, substantially supported by the release of large public datasets. However, these current datasets miss important derived descriptors such as ECG ... ...

Abstract	Machine learning (ML) methods for the analysis of electrocardiography (ECG) data are gaining importance, substantially supported by the release of large public datasets. However, these current datasets miss important derived descriptors such as ECG features that have been devised in the past hundred years and still form the basis of most automatic ECG analysis algorithms and are critical for cardiologists' decision processes. ECG features are available from sophisticated commercial software but are not accessible to the general public. To alleviate this issue, we add ECG features from two leading commercial algorithms and an open-source implementation supplemented by a set of automatic diagnostic statements from a commercial ECG analysis software in preprocessed format. This allows the comparison of ML models trained on clinically versus automatically generated label sets. We provide an extensive technical validation of features and diagnostic statements for ML applications. We believe this release crucially enhances the usability of the PTB-XL dataset as a reference dataset for ML methods in the context of ECG data.
MeSH term(s)	Algorithms ; Electrocardiography/methods ; Machine Learning ; Software ; Humans
Language	English
Publishing date	2023-05-13
Publishing country	England
Document type	Dataset ; Journal Article
ZDB-ID	2775191-0
ISSN	2052-4463 ; 2052-4463
ISSN (online)	2052-4463
ISSN	2052-4463
DOI	10.1038/s41597-023-02153-8
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Article ; Online: Association between primary care electrocardiogram markers and Alzheimer's disease.

Isaksen, Jonas L / Ghouse, Jonas / Skov, Morten W / Olesen, Morten S / Holst, Anders G / Pietersen, Adrian / Nielsen, Jonas B / Maier, Anja / Graff, Claus / Gerds, Thomas A / Frikke-Schmidt, Ruth / Kanters, Jørgen K

Journal of the neurological sciences

2023 Volume 447, Page(s) 120581

Abstract: Objective: The association between common electrocardiogram (ECG) markers and Alzheimer's disease has been scarcely investigated, and it is unknown if ECG markers can improve risk prediction. Thus, we aimed to examine the association between common ECG ... ...

Abstract	Objective: The association between common electrocardiogram (ECG) markers and Alzheimer's disease has been scarcely investigated, and it is unknown if ECG markers can improve risk prediction. Thus, we aimed to examine the association between common ECG markers and Alzheimer's disease in a large population. Methods: We studied the association between ECG markers and Alzheimer's disease using Cox models with adjustment for age, sex, and comorbidities using a large primary care population of patients aged 60 years or more. Results: We followed 172,236 subjects for a median of 7.5 years. Increased PR interval (hazard ratio for PR > 188 ms: 0.76 [95% confidence interval: 0.69-0.83, p < 0.001) and increased QTc interval (hazard ratio for QTc = [426;439]: 0.90 [0.83-0.98], p = 0.02) were associated with a decreased rate of Alzheimer's disease. A positive Sokolow-Lyon index >35 mm (1.22 [1.13-1.33], p < 0.001) and increased T-wave amplitude >4.1 mm (1.15 [1.04-1.27]) were associated with an increased rate of Alzheimer's disease. Upon addition of ECG markers to a reference model, 10-year prediction area under the receiver-operator characteristics curve (AUC) improved by 0.39 [0.06-0.67] %-points. The 10-year absolute risk of Alzheimer's disease was 6.5% and 5.2% for an 82-year old female and a male, respectively, with a favorable ECG, and 12% and 9.2%, respectively, with an unfavorable ECG, almost twice as high. Conclusions: We identified several common ECG markers which were associated with Alzheimer's disease, and which improved risk prediction for Alzheimer's disease.
MeSH term(s)	Female ; Humans ; Male ; Middle Aged ; Aged, 80 and over ; Alzheimer Disease/diagnostic imaging ; Electrocardiography ; Comorbidity ; Biomarkers ; Primary Health Care
Chemical Substances	Biomarkers
Language	English
Publishing date	2023-02-09
Publishing country	Netherlands
Document type	Case Reports ; Journal Article
ZDB-ID	80160-4
ISSN	1878-5883 ; 0022-510X ; 0374-8642
ISSN (online)	1878-5883
ISSN	0022-510X ; 0374-8642
DOI	10.1016/j.jns.2023.120581
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