a b s t r a c t

Objectives: The success of the manual pulse check method frequently employed during cardiopulmonary resus- citation (CPR) is controversial due to its subjective, patient- and operator-dependent, and time-consuming na- ture. carotid ultrasound (c-USG) has recently emerged as an alternative, although there are still insufficient studies on the subject. The purpose of the present study was to compare the success of the manual and c-USG pulse check methods during CPR.

Methods: This prospective observational study was conducted in the critical care area of a university hospital emergency medicine clinic. Pulse checks in patients with non-traumatic cardiopulmonary arrest (CPA) undergo- ing CPR were performed using the c-USG method from one carotid artery and the Manual method from the other. The gold standard in the decision regarding return of spontaneous circulation (ROSC) was the clinical judgment made using the rhythm on the monitor, manual femoral pulse check, end tidal carbon dioxide (ETCO₂), and cardiac USG instruments. The success in predicting ROSC and measurement times of the manual and c-USG methods were compared. The success of both methods was calculated as sensitivity and specificity, and the clin- ical significance of the difference between the methods’ sensitivity and specificity was evaluated Newcombe’s method.

Results: A total of 568 pulse measurements were performed on 49 CPA cases using both c-USG and the manual method. The manual method exhibited 80% sensitivity and 91% specificity in predicting ROSC (+PV: 35%,

-PV: 64%), while c-USG exhibited 100% sensitivity and 98% specificity (+PV: 84%, -PV: 100%). The difference

in sensitivities between the c-USG and manual methods was -0.0704 (95% CI: -0.0965; -0.0466), and the difference between their specificities was 0.0106 (95% CI: 0.0006; 0.0222). The difference between the specific- ities and sensitivities was statistically significant at analysis performed adopting the clinical judgment of the team leader using multiple instruments as the gold standard. The manual method yielded an ROSC decision in 3 +-

0.17 s and c-USG in 2.8 +- 0.15 s, the difference being statistically significant.

Conclusion: According to the results of this study, the pulse check method with c-USG may be superior to the manual method in terms of fast and accurate decision making in CPR.

(C) 2023

1. Introduction

In their Advanced cardiac life support guidelines, both the American Heart Association (AHA) and European Resuscitation Council (ERC) recommend that the time between chest compression and pulse checks be reduced to a minimum [1,2]. The manual method still repre- sents the conventional approach in pulse checks, and although this can

* Corresponding author at: Izmir Katip Celebi University, Ataturk Training and Research Hospital, Department of Emergency Medicine, Basin Sitesi-Izmir 35360, Turkey.

E-mail addresses: [email protected], [email protected] (A. Yamanoglu).

vary from patient to patient, it is still suggested that the carotid artery may be superior to the femoral artery [3].

Manual pulse check is still the most frequently employed method during CPR [4]. However, the success of this conventional method is controversial because of its subjective and patient- and operator- dependent nature [1,2]. Several authors have reported that the manual method can be affected by the experience of health personnel, patient- related factors such as obesity and anatomical deformities, and the patient’s body temperature [1-3]. In addition, even the reliability of pulse checks performed manually by health professionals is open to question [5]. A second handicap with manual pulse checks is their length, with the 10 s recommended by the guidelines being frequently

https://doi.org/10.1016/j.ajem.2023.05.045

0735-6757/(C) 2023

exceeded [6]. All these factors have encouraged several researchers to seek alternative methods on the subject of pulse checks. The method that has attracted the greatest interest among studies involves pulse checks performed using ultrasound (USG). The few recent studies on the subject have reported that pulse checks with USG from the carotid artery may be superior to manual checks [7], with high intra-operator agreement [8,9]. However, the number of studies on this subject is still low, and further investigation of the reliability of pulse checks with carotid USG (c-USG) is needed.

The purpose of this study is to compare c-USG and manual pulse check methods during CPR.

1. Material and method
   1. Study design and setting

This prospective, observational study was performed between De- cember 2021 and November 2022 in the critical care area of a university emergency medicine department. Patients were included in the study during working hours when the study team was present. The hospital’s emergency department critical care unit contains 16 beds with vital finding monitoring, six mechanical ventilator devices, and two portable, one fixed, and one transesophageal USG devices. Interventions on all critically ill patients brought to the emergency department by ambu- lance and presenting as outpatients and CPA cases take place in this area. Approval was granted by the local ethical committee before com- mencement of the study (no. 0536 dated 23.11.2021). Written consent was obtained from the relatives of all patients included in the study. The research was registered with ClinicalTrials under number NCT05557032.

• 1. Study population

All adult patients presenting with in- or out-of-hospital non- traumatic CPA were included in the study. Pregnant women, patients with neck/carotid surgery affecting the application of pulse check palpa- tion and c-USG, with known carotid plaque, with abscess or hematoma in the neck region, with histories of aortic dissection, or with known carotid stenosis were excluded.

• 1. Study protocol and data collection

Before the study commenced, a 12-member team consisting of three emergency medicine teaching staff members and nine senior emer- gency medicine residents was established to perform c-USG and manual pulse checks. A 20-min theoretical training session on practical c-USG was given to the entire team by a faculty member who was part of the team and had been working as an ultrasound instructor in postgraduate training sessions for approximately 10 years since graduation. In the daily work pattern, three members of the teaching staff were present in the hospital during working hours every day, while at least two of the senior residents in the team were assigned to the critical care area and were present to participate in the study in case of CPA. When a case of in-hospital CPA occurred in the emergency department or when a case of CPA was brought to the hospital by ambulance, an an- nouncement was made over the loudspeaker system in the emergency department. The study team assembled in the relevant area following that announcement. Three members of the team were present at each resuscitation and were only involved in the pulse check stage of resuscitation.

In line with the current guidelines, the CPR procedure for patients with CPA began with 100-120 chest compressions a minute. Patients were simultaneously monitored using a LIFEPAK 20e (Stryker, Kalama- zoo, USA) defibrillator. Endotracheal intubation was simultaneously performed on non-intubated patients, and ventilation was provided with 15 l O2, 8-10 times per minute. Following intubation, an EMMA

(Masimo Corporation, Irvine, USA) capnography device measuring end tidal carbon dioxide (ETCO₂) at references intervals of 0-99 mmHg using the mainstream method was installed. Defibrillation was per- formed when Shockable rhythms were observed during CPR. The pulse check procedure was performed by three members of the study team. While one member performed manual pulse checks from the ca- rotid artery, another simultaneously performed c-USG pulse checks from the patient’s other carotid artery. Pulse checks with USG from the carotid artery were conducted using a Mindray M5 model (Medical International Limited, Shenzhen, China) 7-11 MHz lineer probe. The third healthcare professional, the leader of the CPR team, made the final judgment, evaluating rhythm observation on the monitor, manual femoral pulse check, ETCO₂, and if necessary via cardiac USG. Cardiac USG evaluation was performed using a Philips Affiniti 70 model (Philips, Andover, USA) curviLinear probe with a 2-5 MHz frequency through the subxiphoid window. These three operators were blinded to the results of the equipment used by one another and to the judgments made.

The first pulse check following intubation and installation of the capnography device was marked as the beginning of the study. Manual and c-USG pulse checks were performed simultaneously by two practi- tioners at chest compression intervals applied once every two minutes. Each decision-making practitioner recorded decisions regarding pulse and decision times onto case forms without waiting for the team leader who made the ultimate judgment. Cycles with ventricular fibrillation were noted by the team leader, and carotid pulse checks in these cycles were not included in the calculations. In cases of recurrent CPA after ROSC was achieved in the same patient, recurrent pulse check cycles were included in the study. In this case, data for each episode of CPA was analyzed, as opposed to simply each patient. ETCO₂ levels at each pulse check, the rhythm observed on the monitor, cardiac USG results, and the team leader’s final judgment were recorded onto the case re- port form by another senior resident in the study team. CPR was main- tained for at least 20 min until ROSC was achieved or until the exitus decision was made. When the CPR procedure was concluded, the patient’s demographic characteristics, chronic diseases, drugs used, and causes of death in case of exitus patients, were recorded onto the case report form. Patients in whom ROSC was achieved were monitored until either discharge or exitus, and their 24-h and in-hospital clinical outcomes were recorded.

• 1. Outcome measures

The primary outcomes of this study were the manual and c-USG pulse check results measured at the CPR pulse check intervals. The two methods were compared on the basis of the team leader’s final judgment made in the light of the monitor rhythm, manual pulse check, ETCO₂, and cardiac USG instruments. The secondary outcomes were the decision times for the manual and c-USG pulse check methods. The two methods were then compared in terms of decision times.

• 1. Statistical analysis

Descriptive statistics were expressed as frequency, percentage, mean, standard deviation, median, minimum, and maximum values. Number and percentage values were calculated for categorical vari- ables, and mean, median, standard deviation, minimum, and maximum values for numerical variables. Histogram curves, kurtosis and skewness values and the Shapiro-Wilk test were used to determine whether con- tinuous variables were normally distributed. Normally distributed con- tinuous variables were expressed as mean and standard deviation, and continuous variables that did not compatible normal distribution were expressed as median, minimum and maximum values. The Cohen’s Kappa (?) was used to measure reliability of the pulse check methods. Chi-square test was used for comparison of categorical variables in inde- pendent groups and McNemar test was used for comparison in depen- dent groups. The paired t-test was applied in dependent group

comparisons of numerical variables since normal distribution was de- termined. Specific values of manual and c-USG methods (specificity, sensitivity, positive predictive value (PPV) and negative predictive value (NPV)) were calculated. Sensitivity and specificity values of man- ual and c-USG method were compared simultaneously using the Newcombe method, the success of which has been confirmed by vari- ous previous studies [10] and which is capable of performing compari- sons based on prevalences and clinical significance [11]. Since normality of distribution was not established, the Mann Whitney U test was applied in the comparison of the methods’ time durations in in- dependent groups and Wilcoxon test was applied in dependent groups. Statistical calculations were performed on SPSS version 24.0 software and with Newcombe’s formula. All calculations were performed at a 95% confidence interval. p values <0.05 were regarded as statistically significant.

1. Results

One hundred twenty-nine patients with CPA presented during the team’s working hours throughout the course of the study, 49 of whom met the inclusion criteria and were enrolled in the study. A work flow chart is shown in Fig. 1. Twenty-seven (55%) of the patients included in the study had in-hospital CPA, the mean age of the all included pa- tients was 69 +- 17 years, and 25 (51%) were women. The patients’ de- mographic characteristics and general descriptive data for CPA are shown in Table 1.

A total of 595 pulse check intervals occurred in the 49 patients who underwent CPR. VF and pulseless VT developed in 27 of these pulse check intervals, and defibrillation was performed as soon as rhythm was observed, without pulse checks by team leader. Both manual and c-USG pulse checks were performed in the remaining 568 intervals and included in the analyses. Firstly, the compatibility between the c- USG method, the manual method and the clinical judgment was

checked. The % of agreement 98.9 was found between the c-USG and clinical judgment, and Cohen’s ? was 0.90 (95% CI: 0.84; 0.96), indicat- ing almost perfect agreement. The % of agreement 90.8 was found be- tween the manuel method and clinical judgment. Cohen’s ? was 0.44 (95% CI: 0.34; 0.54), indicating moderate agreement. The % of agree- ment 89.9 was found between the c-USG and manual method. Cohen’s ? was 0.41 (95% CI: 0.31; 0.51), indicating moderate agreement. Com- parative analysis were performed after the compatibility analysis. The comparison of the final clinical judgment of the team leader and the manual pulse check method is presented in Table 2. The accuracy of the manual pulse check method was found to be 91% (CI 95%: 88%- 93%) and pulse check time was significantly lower than clinical decision process. Secondly, the clinical judgment and the c-USG pulse check method were compared. The accuracy of the c-USG pulse check method was found to be 99% (CI 95%: 98%-100%) and pulse control time was sig- nificantly lower than clinical decision process (Table 3). Finally, the manual pulse check method and the c-USG pulse check method were compared with each other. In the comparison, it was seen that the pulse check results of both methods were statistically different from each other, and it was seen that the c-USG pulse check method took a faster decision than the manual pulse check method (Table 4).

Following calculation of test success rates such as sensitivity and specificity for the manual and c-USG methods, Newcombe’s method was applied to test the clinical significance in the difference in success between the two methods. The clinical decision made by the team leader using multiple instruments was regarded as the gold standard, and the difference in sensitivity between the manual and c-USG methods was -0.0704 (95% CI: -0.0965; -0.0466). Since the confi- dence interval did not contain a zero value, the difference in sensitivity was regarded as statistically significant. The difference in specificity be- tween the manual and c-USG methods using the clinical decision as the gold standard was 0.0106 (95% CI: 0.0006; 0.0222). Since the confidence interval did not contain a zero value, the difference in specificity was

Fig. 1. Work Flow Chart.

Cardiopulmonary arrest: CPA.

Table 1

The patients’ demographic characteristics and general cardiopulmonary resuscitation data.

General characteristics

Table 3

Comparison of c-USG pulse check method with clinical judgment.

c-USG pulse check method

Clinical judgment Positive Negative Total P value

Age (mean +- SD)	69 +- 17
Gender-female n (%) Chronic diseases n (%)	25 (51%) Only CAD	7 (14%)
	HT	11 (22%)

Positive Negative	31 6	0 531	31 537	0.031?
Total	37	531	568

CVD CKD COPD

DM	6 (12%)		Sensitivity: 100% (89-100), Specificity: 98%
CHF	3 (6%)	Test success	(98-100), +PV: 84% (70-92), -PV: %100

Two or more chronic diseases

3 (6%)

5 (10%)

1 (2%)

13 (27%)

Pulse check time (sec) (mean +- SD)

Clinical judgment c-USG pulse check

method <0.001??

5.9 +- 1.7 2.8 +- 0.15

Cardiopulmonary resuscitation data c-USG: Carotid ultrasound.

Localization of CPA (Number of patiens (%)) Outcome of CPA patients (Survived - Died)

Rhythms cycles seen in chest compression pauses

IHCA OHCA

Survived Died

Arrest rhythms Asystole

PEA

VF/ Pulseless VT ROSC rhythms Sinusoidal rhythm Atrial fibrillation

27 (55%)

22 (45%)

17 (35%)

32 (65%)

564 (100%)

500 (89%)

37 (6%)

27 (5%)

31 (100%)

25 (80%)

6 (20%)

* McNemar test p value.

?? Wilcoxon test p value.

to compare the statistical and methodological success of the two methods. In present study, the c-USG pulse check method was found to be superior to the manual method in terms of both time and of the correct decision being made, and the difference between the two methods was statistical and methodological significant based on the gold standard method. The statistical and methodological significance

of the difference between the specificities of both measurement

ETCO₂ (mean +- SD) ROSC (measured in 31 cycles) 23 +- 3.8 mmHg

EX (measured in 537 cycles) 14 +- 4.5 mmHg

CAD: coronary artery disease, HT: hypertension, DM: diabetes mellitus, CHF: chronic heart failure, CVD: chronic vascular disease. CKD: chronic kidney disease, COPD: chronic ob- structive pulmonary disease, CPA: Cardiopulmonary arrest, CPR: Cardiopulmonary resus- citation, PEA: Pulseless electrical activity, VF: ventricular fibrillation, SD: Standard deviation, ETCO_2: End tidal carbon dioxide IHCA: In-hospital cardiopulmonary arrest OHCA: out-of-hospital cardiopulmonary arrest, ROSC: return of spontaneous circulation, EX: exitus. SD: Standard deviation.

also regarded as statistically significant. The Newcombe method test re- sults are shown in Table 5. The relationship between the simultaneous difference of sensitivity and specificity of the manual and c-USG methods based on the gold standard method is shown in Fig. 2.

1. Discussion

Manual pulse check method is widely used for pulse checking at CPR, although several studies have shown that this method is operator- and patient-dependent, has low reliability, especially in ROSCs with low car- diac output, and is affected by several factors including cold and obesity [6,12-14]. Concerns have therefore recently arisen concerning manual pulse checks, and a search for alternative pulse check methods has begun [7,15]. The most notable of such studies are those using pulse checks with USG [7,16]. The present study is one of the rare studies eval- uating the success of c-USG, and to the best of our knowledge is the first

Table 2

Comparison of manual pulse check method with clinical judgment.

Manual pulse check method

methods was less, while the difference between their sensitivities was higher.

The weaknesses of the manual pulse check method in making the accurate decision as well as in making quick decisions are among the current subjects of debate. Dick et al. reported that the manual pulse check method was able to make a decision about the pulse status within the recommended 10 s in only 16% of the study population [6]. Zengin et al. reported a mean manual pulse check control duration of 9.29 s [17], and Yamane D. et al. a figure of 11.5 s [18]. In contrast to those studies, the mean manual pulse check duration in the present study was 3 +- 0.17 s. Similarly to present study, Kang et al. reported a mean duration of 3.50 s [7]. These results support the idea of the subjective na- ture of manual pulse checks. The manual method is known to be depen- dent on the patient and the experience of the applicator, and the main reason for the inconsistencies between studies may be that they in- volved different populations and applicators with different levels of ex- perience.

In terms of studies involving USG, Zengin et al. reported a duration of pulse check with c-USG of 7.60 s, significantly shorter than the manual pulse check method [17]. However, in contrast to other studies, Kang et al. performed pulse checks using the carotid artery compression method and reported a mean duration of 1.62 s, shorter than in all sim- ilar studies and shorter than with the manual method. The pulse check duration with c-USG in the present study was 2.8 s, significantly shorter than the manual method. In contrast to all these studies, C. Allison et al. compared the manual pulse check method with femoral artery USG and also reported a higher rate of accuracy with pulse checks using USG [19]. Although the pulse check duration varies among different studies, methods using USG were superior to the manual method in terms of both pulse check duration and accuracy. Although measurement dura-

Clinical judgment		Positive	Negative	Total	P value		tions vary depending on the applicator and the different patient popula-
	Positive	25	6	31			tions, the use of USG appears to be superior in terms of accuracy and
	Negative	46	491	537	<0.001?		duration in all studies, including the present study.
	Total	71	497	568

Test success

Sensitivity: 80% (61-91),

Specificity: 91% (89-93), +PV:

35% (24-47), -PV: 98% (97-99)

1. Limitations

In this study, consistent with the majority of studies evaluating the

Pulse check time (sec) (mean

+- SD)

Clinical judgment

Manual pulse

check method <0.001??

success of USG in pulse checks, the gold standard was the clinical judg- ment made by the team leader using multiple instruments. However,

* McNemar test p value.

?? Wilcoxon test p value.

5.9 +- 1.7 3 +- 0.17

the Arterial line has been employed as the gold standard in some studies [19]. Although arterial line is a more objective and more successful method to evaluate ROSC in CPR, its use in clinical practice is limited.

Table 4

Comparison of c-USG pulse check method with manual pulse check method

Pulse measurement data

c-USG pulse check method Manual pulse check method P value

Pulse detected (n) 37 71

No pulse (n) 531 497

<0.001?

Test success Sensitivity: 100% (89-100), Specificity:

98% (98-100), +PV: 84% (70-92), -PV: %100

Sensitivity: 80% (61-91), Specificity: -

91% (89-93), +PV: 35% (24-47), -PV: 98% (97-99)

Pulse check time (sec) (mean +- SD)

c-USG: Carotid ultrasound.

* McNemar test p value.

?? Wilcoxon test p value.

2.8 +- 0.15 3 +- 0.17 <0.001??

Table 5

Comparison of the difference between the sensitivities and specificities of the manual pulse ceheck method and the c-USG pulse ceheck method based on clinical judgment

Sensitivity Specificity

In the present study, the team leader who made the clinical decision, the team members who made the c-USG measurements and the manual measurements were working on the same patient. All indicators such as ETCO2, cardiac monitoring measurements were adjusted according to

the team leader. The team members who made the other measure-

Manual pulse check method

c-USG pulse check method

80% (95% CI: 61-91) 91% (95% CI: 89-93)

100% (95% CI: 89-100) 98% (95% CI: 98-100)

ments kept their own measurement times and records with the stopwatch and decided before the team leader in almost all measure- ments. Although team members are busy with their assigned work, it

Simultaneous differences

-0.0704 (95% CI: -0.0965 to

-0.0466)

0.0106 (95% CI: 0.0006 to

0.0222)

is possible that team members are influenced by each other and other metrics. This may be another limitation of the study.

Simultaneous difference for sensitivity; It is the ratio of the difference between the num- ber of positive patients detected by the gold standard test and the number of positive pa- tients detected by the test A to the total number of patients.

Simultaneous difference for spesifity; It is the ratio of the difference between the number of negative patients detected by the gold standard test and the number of negative pa- tients detected by the test B to the total number of patients.

The use of this method in emergency and acute situations such as CPA is only possible with experienced practitioners and in limited populations such as intensive care patients with in-hospital cardiac arrest and/or who already have an arterial line. For this reason, the “clinical judg- ment” method, which is widely used and accepted all over the world, can be considered as an appropriate gold standard method for compar- ing c-USG and manual pulse check in emergency room patients, most of whom have out-of-hospital cardiac arrest.

Fig. 2. Graph of simultaneous differences between sensitivies and specificities of c-USG/ manual methods based on gold standard method.

Blue line: Differences between sensitivies and specificities of c-USG and manual methods. Red line: Confidence intervals differences between sensitivies and specificities of c-USG and manual methods.

Lambda (?): ? which takes values between 0 and 1, represents the clinical cost of false positive and false negative and the occasion posing serious problems for the prevalence value belonging to the population to which tests are administered.

In most of the studies, despite the use of different gold standards, pulse checks using USG have been found to be superior to the manual pulse check method. However, in most of all these studies, including present study, only the results of the manual pulse check method were compared with the results of the USG pulse check method. Whereas, in practice, even if USG is used for pulse check, some instru- ments such as monitor rhythm and ETCO₂ measurements will still be used. Therefore, in new studies, comparing the addition of other instruments to the manual pulse check method with the addition of other instruments to the c-USG pulse check method may yield more valuable results for real clinical practice. Although c-USG method is su- perior when only two methods are compared, the success rate may change when used with other instruments in practice.

One of the important limitations of this study is that it is single- centered and the study was carried out only during working hours when the study team was present. Therefore, the number of patients admitted to the study remained relatively low. These limitations may constrain the generalizability of the study result. However, the effect of this limitation was probably low, as the number of measurements, rather than the number of patients, was reflected in the statistical anal- ysis in this study. In addition, in this study, inter-rater reliability was not evaluated for the check of carotid pulse with USG. The senior residents and faculty members who measured in this study had experience with emergency ultrasound in daily practice, and all practitioners received training in c-USG prior to the study. Therefore, although no difference is expected between them in a basic issue such as detecting the beat in carotid ultrasound, it is shoul be considered a limitation.

1. Conclusions

In this study, pulse checks using c-USG were superior to the manual method in terms of both pulse check time and accurate decision making. The difference in decision making accuracy between the manual and c- USG methods was statistical and methodological significant based on gold standard method. Further studies are needed to confirm this.

Author contributions statement

Conception and design: Sercan Ozlu, Serkan Bilgin, Adnan Yamanoglu, Osman Sezer Cinaroglu, Davut Tekyol; the definition of in- tellectual content: Sercan Ozlu, Serkan Bilgin, Adnan Yamanoglu, Osman Sezer Cinaroglu, Mehmet Goktug Efgan, Ahmet Kayali, Davut

Tekyol; literature search, clinical studies, experimental studies, data ac- quisition, data analysis: Adnan Yamanoglu, Osman Sezer Cinaroglu, Mehmet Goktug Efgan, Ahmet Kayali, Davut Tekyol; manuscript prepa- ration, manuscript editing, and manuscript review: Sercan Ozlu, Serkan Bilgin, Adnan Yamanoglu, Osman Sezer Cinaroglu, Mehmet Goktug Efgan; final approval of the version to be published: Sercan Ozlu, Serkan Bilgin, Adnan Yamanoglu, Osman Sezer Cinaroglu, Mehmet Goktug Efgan, Ahmet Kayali, Davut Tekyol; for all aspects of the work in ensur- ing that questions related to the accuracy and integrity appropriately in- vestigated and resolved: Sercan Ozlu, Serkan Bilgin, Adnan Yamanoglu, Osman Sezer Cinaroglu, Mehmet Goktug Efgan, Ahmet Kayali, Davut Tekyol.

Guarantor author

Adnan Yamanoglu.

Sources of support and funding

Not available.

CRediT authorship contribution statement

Sercan Ozlu: Visualization, Validation, Supervision, Resources, Pro- ject administration, Methodology, Investigation, Formal analysis, Data curation. Serkan Bilgin: Visualization, Supervision, Methodology, Investigation, Funding acquisition, Formal analysis, Data curation, Con- ceptualization. Adnan Yamanoglu: Writing - review & editing, Writing - original draft, Visualization, Software, Resources, Project administra- tion, Methodology, Investigation, Funding acquisition, Formal analysis, Conceptualization. Ahmet Kayali: Visualization, Validation, Supervi- sion, Resources, Project administration, Funding acquisition, Formal analysis, Data curation, Conceptualization. Mehmet Goktug Efgan: Writing - review & editing, Visualization, Supervision, Resources, Meth- odology, Investigation, Funding acquisition, Formal analysis, Data curation, Conceptualization. Osman Sezer Cinaroglu: Writing - review & editing, Writing - original draft, Validation, Software, Resources, Methodology, Investigation, Formal analysis, Conceptualization. Davut Tekyol: Writing - original draft, Supervision, Software, Resources, Methodology, Investigation, Conceptualization.

Declaration of Competing Interest

Sercan Ozlu, Serkan Bilgin, Adnan Yamanoglu, Osman Sezer Cinaroglu, Mehmet Goktug Efgan, Ahmet Kayali, Davut Tekyol declare that they have no conflict of interest.

Acknowledgements

Not available.

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