Inter Observer Agreement Among Radiologist and Otorhinolaryngologists on Paranasal Sinus Computed Tomography Scans in Chronic Rhinosinusitis

Abstract

To evaluate inter observer agreement between Radiologist and Otorhinolaryngologists in identifying important structures and pathologies on pre operative computed tomography (CT) scans of paranasal sinus (PNS) in chronic rhinosinusitis (CRS). A retrospective review of CT scans PNS of CRS patients. Archived CT scans were evaluated by 3 observers, similarly experienced radiologist and otorhinolaryngologist and a less experienced otorhinolarygologist. The degree of intra- as well as inter observer agreement was assessed by Cohen’s kappa statistics. A moderate and a fair inter observer agreement was noted among experienced radiologist and otorhinolaryngologist; & experienced experts and less experienced otorhinolaryngologist respectively. The greatest disagreements among all observers were found in superior attachment of uncinate process, optic nerve’s relationship with sphenoid sinus and dehiscence of anterior ethmoid canal. The present study demonstrated a considerable inter observer variability among radiologists and otorhinolaryngologists, irrespective of their experience in the field of speciality. A few critically important structures which showed an unsatisfactory level of agreement and thus need to be sought after with more training and practice, were also identified. These included Keros type, optic nerve’s location, dehiscence of anterior ethmoid artery, vidian and maxillary nerves, lamina papyracia defect, sphenoid sinus pneumatization and attachment of uncinate process. The study also emphasized the importance of inter disciplinary conferences for pre operative evaluation of sinus CT scans of CRS patients.

Introduction

Chronic rhinosinusitis (CRS) is a common and significant health problem affecting 5–12% of the general population worldwide [1]. It poses a significant burden, on those affected as well as the society, in terms of healthcare consumption and loss of productivity in relation to both physical and psychosocial state. Hence, a prompt diagnosis and planned management is mandatory. Besides thorough clinical history and examination, various imaging modalities like conventional X-ray, computerized tomography (CT), cone beam CT and magnetic resonance imaging (MRI) have proven to be a backbone in diagnosis of CRS and for assessing the severity of disease as well as pre operative planning [1]. Overall CT scan paranasal sinus remains the gold standard in radiological evaluation of CRS. With its introduction and increasing use in the last twenty years, it has immensely contributed to surgeon’s expertise to appreciate the nuances of PNS anatomy and correlation of disease along with surgical planning [2].

Paranasal sinuses (PNS) are very well known to have numerous anatomical variations and hence evaluation of CT scan PNS by a surgeon is of paramount importance during pre surgical planning in view of anatomical variations, pathological structures as well as surgical approaches [3, 4]. Functional endoscopic sinus surgery (FESS) is the standard surgical intervention in CRS. CT scans are again the gold standard in planning of FESS and thus knowledge of critical structures and their identification before proceeding with FESS helps in decreasing inadvertent complications that may actually be avoidable [5]. If a surgeon or a surgical team understands what structures need special considerations or are usually under identified by them, they can actively put an effort to enhance their skill in identification of such structures which will in turn help in better surgical planning and patient outcome.

Despite a widespread use of CT scans in diagnosis of CRS and its management, a difference in the observer perspective among Radiologists and Otorhinolaryngologists has been noted [5]. Even the residents and newly certified specialists, both in radiology and otorhinolaryngology, accept the struggle they encounter in reporting and operation planning and classifying and grading of various structures [6]. There have been previous studies in other specialities which have concluded that there is a major difference between an experienced and an inexperienced observer while evaluating inter observer agreements in reproducibility of CT scans. Some have concluded moderate inter observer agreement [7, 8] between observers of varied experience and even among equally experienced observers of different expertise [9]. In otorhinolaryngology, there is a scarcity of evidence on inter observer agreement with respect to CT scan PNS. To the best of author’s knowledge, there are only 2 such studies. One study just focussed on radiological assessment of only a few structures, that too confined to coronal plane scans [10]. The other study did not analyse some of the critical structures including sphenoid sinus and related nerve dehiscences [11]. Hence, the current study aimed to evaluate inter observer agreement between Radiologist and Otorhinolaryngologists (with similar as well as varied years of experience) in identifying important structures and pathologies on pre operative CT scans of PNS, with respect to surgical intervention in CRS. This in turn allowed us to appreciate and identify critical structures with low inter observer agreement so that special emphasis could be given during academic training. The hypothesis of this study is that there exists a ‘good’ inter observer agreement between Radiologist and Otorhinolaryngologists in evaluating CT paranasal sinuses.

Methods

The current study was conducted as a retrospective review of CT scans of PNS of CRS patients, between 1^st August, 2020 and 31st May, 2021 after obtaining permission from the institutional ethics committee. Archived CT scans of PNS of patients diagnosed as CRS were evaluated by 3 observers, one experienced (10 years) Radiologist, another experienced (10 years) Otorhinolaryngologist and one less experienced Otorhinolarygologist (1 year). Scans of postoperative cases or pathology causing bony destruction and with previous facial or anterior skull base trauma, were excluded. A total of 89 scans qualified for the study, out of which 50 scans were randomly selected using a computer generated sequence, to be included in the study. All observers underwent an initial training of one week, under a certified radiologist (not part of study). Each observer was provided a checklist (Appendix) that included the structures and the radiological scoring/staging system, they were expected to identify and evaluate. This checklist was prepared keeping in mind the studies providing a basic format for reporting pre FESS CT [12–14]. It consisted of multiple parameters usually following the order in which they are approached during FESS. The structures included those critical for surgical planning like depth of olfactory fossa, optic nerve relation, lamina papyracea, sphenoid sinus and related neurovascular structures and others. Demographic and personal details were extracted from the records. Each observer evaluated the scans independently and was blinded to patient’s demographic and clinical details and the official radiological report. He/she was also blinded to the other observer’s rating. Incomplete reporting was excluded. After an interval of three weeks, each CT scan (from the included sample) was provided to each observer again to be re-evaluated. This second dataset was used to generate inter-observer consistency. Both the observation datasets were used to assess intra-observer consistency. IBM SPSS statistics version 26 was used for the data analysis. The degree of intra- as well as inter observer agreement was assessed by Cohen’s kappa statistics and latter was based on the data from second observation. Cohen’s kappa (k) is based on the difference between agreement which is actually present compared to the degree of agreement expected to be present by chance alone. Kappa value was calculated for agreement between radiologist and experienced otorhinolaryngologist, radiologist and less experienced otorhinolaryngologist and both otorhinolaryngologists._. Interpretation of kappa statistic (which ranges from − 1 to + 1) was done using following classification [15].

Poor < 0.2

Fair = 0.21–0.4

Moderate = 0.41–0.6

Good = 0.61–0.8

Very Good = 0.81–1.0

A negative kappa statistic denotes that the agreement is worse than what is expected by chance alone. p values of < 0.05 were considered statistically significant.

Results

50 CT scans of patients with CRS, obtained as part of standard clinical care at our institution were reviewed. All scans were observed by three independent observers, blinded to each other and to the patient history data. Majority of patients were males (Male: Female = 1.27:1). Mean age of the patient was 34.22 ± 6.582 years (Range: 25–52 years). Most of the patients had allergic rhinitis (58%) whereas 22% were asthmatics. History of tobacco smoking was present in 14 patients. Out of 50 CRS patients, 68% were with nasal polyps. The predominant clinical complaint was of nasal obstruction (84%) followed by headache (34%).

When the agreement between radiologist and otorhinolaryngologist, with similar experience, was evaluated, ‘moderate’ inter observer agreements were detected in majority of structures. As evident from Table 1, the greatest agreements were demonstrated among pneumatized middle turbinate (k = 0.880 right side and k = 0.841 left side), nasal septum deviation (k = 0.874 right side and k = 0.836 left side) and pneumatization (k = 1.000). The greatest disagreements were found in superior attachment of uncinate process (k = 0.235 right side and k = 0.269 left side), optic nerve’s relationship with sphenoid sinus (k = 0.259 right side and k = 0.319 left side) and dehiscence of anterior ethmoid canal (k = 0.278 right side and k = 0.327 left side).

Table 1.

Inter observer agreement values—experienced Radiologist versus experienced Otorhinolaryngologist

Sinonasal parameters	Cohen’s kappa (right side)	p value	Cohen’s kappa (left side)	p value
Deviated nasal septum	0.874	0.000	0.836	0.000
Septum pneumatization	1.000	0.000	–	–
Inferior turbinate hypertrophy	0.606	0.000	0.498	0.000
Uncinate Process superior attachment	0.235	0.022	0.269	0.009
Middle turbinate pneumatization	0.880	0.000	0.841	0.000
Middle turbinate variants	0.372	0.001	0.439	0.000
Haller cell	0.429	0.001	0.499	0.000
Frontal cell type	0.380	0.000	0.376	0.000
Supraorbital cell	0.321	0.006	0.473	0.000
Maxillary sinus accessory ostium	0.310	0.002	0.563	0.000
Intra maxillary sinus septation	0.680	0.000	0.752	0.000
Dehiscent infraorbital nerve	0.468	0.000	0.502	0.000
Keros type	0.399	0.000	0.451	0.000
Anterior ethmoid artery dehiscence	0.278	0.044	0.327	0.012
Lamina papyracia dehiscence	0.485	0.000	0.457	0.001
Sphenoid sinus pneumatization	0.524	0.000	0.560	0.000
Optic nerve	0.259	0.009	0.319	0.002
Vidian nerve dehiscence	0.369	0.009	0.429	0.002
Maxillary nerve dehiscence	0.302	0.031	0.379	0.007
Lund Mackay score	0.524	0.000	0.689	0.000

When the agreement between the experienced radiologist and less experienced otorhinolaryngologist was assessed, on an average, only ‘fair’ agreement was noted. Table 2 shows that the structures like pneumatization of sphenoid sinus (k = 0.091 right side and k = 0.074 left side), dehiscence of foramen rotundum (k = 0.151 right side and k = 0.135 left side), relation of optic nerve with sphenoid sinus (k = 0.199 right side and k = 0.176 left side) and anterior ethmoid canal dehiscence (k = 0.138 right side and k = 0.163 left side) demonstrated ‘poor’ agreement. On the other hand, a ‘good’ agreement was observed among pneumatization of middle turbinate (k = 0.760 right side and k = 0.720 left side). Pneumatization of nasal septum depicted a ‘perfect’ agreement (k = 1).

Table 2.

Inter observer agreement values—experienced Radiologist versus less experienced Otorhinolaryngologist

Sinonasal parameters	Cohen’s kappa (right side)	p value	Cohen’s kappa (left side)	p value
Deviated nasal septum	0.280	0.041	0.235	0.094
Septum pneumatization	1.00	0.000	–	–
Inferior turbinate hypertrophy	0.292	0.036	0.293	0.034
Uncinate Process superior attachment	0.213	0.022	0.213	0.022
Middle turbinate pneumatization	0.760	0.000	0.720	0.000
Middle turbinate variants	0.257	0.024	0.151	0.171
Haller cell	0.444	0.000	0.519	0.000
Frontal cell type	0.209	0.002	0.231	0.001
Supraorbital cell	0.399	0.001	0.239	0.029
Maxillary sinus accessory ostium	0.390	0.005	0.333	0.018
Intra maxillary sinus septation	0.307	0.030	0.213	0.125
Dehiscent infraorbital nerve	0.432	0.002	0.432	0.002
Keros type	0.222	0.037	0.255	0.017
Anterior ethmoid artery dehiscence	0.138	0.054	0.163	0.090
Lamina papyracia dehiscence	0.380	0.001	0.396	0.003
Sphenoid sinus pneumatization	0.091	0.470	0.074	0.529
Optic nerve	0.199	0.023	0.176	0.048
Vidian nerve dehiscence	0.259	0.006	0.355	0.008
Maxillary nerve dehiscence	0.151	0.043	0.135	0.057
Lund Mackay score	0.521	0.000	0.545	0.000

Similarly, overall agreement between an experienced otorhinolaryngologist and less experienced otorhinolaryngologist was only ‘fair’. The greatest disagreements was observed among dehiscences of vidian foramen (k = 0.021 right side and k = 0.047 left side), foramen rotundum (kappa = 0.121 right side and 0.121 left side), and infraorbital foramen (k = 0.202 right side and k = 0.155 left side). Pneumatization of middle turbinate (k = 0.641 right side and k = 0.640 left side) and its anatomical variants (k = 0.840 right side and k = 0.603 left side) demonstrated a ‘good’ agreement along with a ‘perfect’ agreement in nasal septum pneumatization (k = 1) (Table 3).

Table 3.

Inter observer agreement values—experienced Otorhinolaryngologist versus less experienced Otorhinolaryngologist

Sinonasal parameters	Cohen’s kappa (right side)	p value	Cohen’s kappa (left side)	p value
Deviated nasal septum	0.400	0.004	0.274	0.049
Septum pneumatization	1.00	0.000	–	–
Inferior turbinate hypertrophy	0.393	0.005	0.322	0.023
Uncinate Process superior attachment	0.258	0.008	0.259	0.008
Middle turbinate pneumatization	0.641	0.000	0.640	0.000
Middle turbinate variants	0.840	0.000	0.378	0.007
Haller cell	0.561	0.000	0.508	0.000
Frontal cell type	0.210	0.028	0.124	0.193
Supraorbital cell	0.490	0.000	0.494	0.000
Maxillary sinus accessory ostium	0.380	0.001	0.459	0.001
Intra maxillary sinus septation	0.389	0.003	0.364	0.004
Dehiscent infraorbital nerve	0.202	0.091	0.155	0.241
Keros type	0.300	0.001	0.317	0.001
Anterior ethmoid artery dehiscence	0.233	0.010	0.355	0.004
Lamina papyracia dehiscence	0.540	0.000	.5580	0.000
Sphenoid sinus pneumatization	0.272	0.048	0.240	0.077
Optic nerve	0.512	0.000	0.408	0.000
Vidian nerve dehiscence	0.021	0.832	0.047	0.065
Maxillary nerve dehiscence	0.121	0.072	0.121	0.072
Lund Mackay score	0.605	0.000	0.506	0.000

Intra observer consistency was assessed for each observer. As noted in Table 4, both the experienced observers showed ‘very good’ consistency in identification of almost all the structures. The less experienced otorhinolaryngologist did show somewhat lesser degree of consistency compared to the more experienced colleagues. This was especially true for nerve dehiscences (maxillary and vidian) and uncinate process superior attachment. However, the lowest level of consistency for the less experienced otorhinolaryngologist was still categorized as ‘good’ by Cohen’s kappa values.

Table 4.

Intra observer agreement values (Cohen’s kappa)

Sinonasal parameters	Experienced Radiologist	Experienced Otorhinolaryngologist	Less experienced Otorhinolaryngologist
Maxillary sinus accessory ostium	0.898	0.753	0.878
Anterior ethmoid artery dehiscence	0.957	0.944	0.834
Middle turbinate pneumatization	0.960	0.940	0.900
Dehiscent infraorbital nerve	0.921	0.819	0.905
Optic nerve	0.872	0.912	0.836
Deviated nasal septum	0.958	0.937	0.920
Frontal cell type	0.957	0.948	0.838
Haller cell	0.950	0.932	0.795
Intra maxillary sinus septation	0.947	0.926	0.928
Inferior turbinate hypertrophy	0.959	0.953	0.905
Keros type	0.829	0.824	0.837
Lamina papyracia dehiscence	0.939	0.939	0.856
Lund Mackay score	0.940	0.913	0.887
Maxillary nerve dehiscence	0.861	0.812	0.658
Middle turbinate variants	0.939	0.899	0.840
Septum pneumatization	0.935	0.875	0.805
Sphenoid sinus pneumatization	0.877	0.840	0.816
Supraorbital cell	0.928	0.910	0.895
Uncinate Process superior attachment	0.844	0.815	0.693
Vidian nerve dehiscence	0.952	0.883	0.768

Discussion

The purpose of this study was to evaluate inter observer agreement between Radiologist and Otorhinolaryngologists (with similar as well as varied years of experience) in identifying important structures and pathologies on pre operative CT scans of PNS, with respect to surgical intervention in CRS. The study has demonstrated that there is a possibility of considerable variation among observers in evaluating CT scans PNS. Although, both experienced radiologist as well as otorhinolaryngologist agreed well for structures like pneumatization of nasal septum, middle turbinate pneumatization and nasal septum deviation, there were several structures with merely ‘fair’ inter observer agreement including some critical structures like Keros type, optic nerve’s location, dehiscence of anterior ethmoid artery, vidian and maxillary nerves and superior attachment of uncinate process. Similarly, among multiple important structures like optic nerve’s location, dehiscence of vidian canal, foramen rotundum, anterior ethmoid canal and infraorbital foramen, the less experienced otorhinolaryngologist demonstrated ‘poor’ agreement when compared with experienced experts in their respective fields. There has been a similar previous attempt to evaluate inter observer agreement of paranasal sinus CT scans between a radiologist, an Ear, nose and throat (ENT) surgeon, and an ENT resident by Julkunen A et al. [11]. They found an overall moderate inter observer agreement between all the observers. They did identify certain structures like optic nerve, insertion of uncinate process, anterior ethmoidal artery, and Keros class, which had ‘poor’ inter observer agreement. In their analysis, the overall agreement between radiologist and ear nose & throat resident were ‘moderate’, whereas agreement was ‘fair’ between radiologist and ear nose & throat surgeon as well as between ear nose & throat surgeon and ear nose & throat resident. In contrast, our results deviate slightly as we observed a better agreement between experienced radiologist and otorhinolaryngologist when compared to the level of agreement between them and less experienced otorhinolaryngologist. In another study by Guarnizo A et al., a poor inter observer agreement in the assessment of dehiscence of anterior ethmoid canal on CT scan PNS among two neuroradiologists with 10 years of experience was noted [16].

Other similar evaluations, albeit in another domains, reported a fair to moderate agreement on reporting of CT arthrograms among two radiologists [9] and moderate agreement among 8 neuroradiologists in the interpretation of head CT Scans [17]. Another study reported only moderate inter observer agreement among thoracic radiologists, irrespective of their experience [18].

Owing to the vast detailed knowledge required regarding anatomical details and variations, it appears that there are different ways to evaluate CT scans of paranasal sinuses and related structures, and the only correct one cannot be fully determined. This has led to multiple proposed formats of reporting of scans previously, including some well constructed forms and some textual formats [12, 19]. An exhaustive pre surgery CT checklist has been proposed including multiple anatomical structures [20]. The authors tried to incorporate all those significant structures from the published available formats required to be assessed before endoscopic sinus surgery and utilised the compiled checklist in the current study for evaluation of CT scans of PNS. Based on the checklist, the authors also tried to highlight those structures with lack of satisfactory agreeability among observers. Among the parameters assessed, some operatively critical structures which had a significant disagreement among all 3 observers included Keros type, optic nerve’s location, dehiscence of anterior ethmoid artery, vidian and maxillary nerves, lamina papyracia defect, sphenoid sinus pneumatization and attachment of uncinate process. All these structures play very crucial role in success of endoscopic sino-nasal surgeries and need to be identified cautiously. These are also in accordance with a recent study which identified these anatomical structures to hold a greater surgical importance [21]. Uncinate process has a variable superior attachment and pattern of attachment determines the position of frontal sinus drainage pathway along with various types of frontal cells. The lamina papyracea which forms the lateral walls of the ethmoid sinuses mark a very important operative landmark and its defects mandate preoperative documentation to avoid inadvertent orbital injury. The anterior ethmoidal artery has a normal bony covering, which may be absent leading to dehiscent artery being suspended on a mucous membrane mesentery, increasing the risk of intraoperative intractable haemorrhage. Keros classification telling about the depth of olfactory fossa indicates associated risk of intra operative injury and iatrogenic cerebrospinal fluid leak in this region. Pneumatization pattern of sphenoid sinus along with bony dehiscences of vidian nerve and maxillary nerve determines the degree of intra operative risk of damage to these vital structures. Anatomical relations of optic nerve with sphenoid sinus indicated by DeLano [22] classification plays a vital role in preventing iatrogenic nerve injury.

The high level of disagreements in these parameters among various observers could be partly attributed to variability in definitions and classification systems along with their inherent subjective interpretation. For example, in the terminology adopted by DeLano, the limits between types 3 and 4 are not clear and some authors have tried a modification to distinguish these types clearly [23].

Though the authors, in current study, used standardised definitions of bony dehiscences, one should not ignore the fact that it is difficult to differentiate extremely thin and dehiscent bone, even with the advances in the ability of high resolution CT to accurately identify dehiscence, thus adding to the inter observer variability. Defining bony dehiscences as well as depth of olfactory fossa on CT is subjected to both inter and intra observer differences, as also observed previously [24].

The complex anatomy of structures surrounding the frontal sinus drainage pathway, including uncinate process, specially its superior attachment reflects the lack of agreement regarding anatomical variants of this region [25].

Tracing back, twenty years ago also, literature suggested a suboptimal agreement among five surgeons specially on identification of bony anomalies on coronal CT of paranasal sinuses [10]. The authors then also suggested the need for uniform and accurate definitions and various classifications in order to reduce confusion. Another subjective evaluation have recently highlighted a discomfort among a notable number of experienced otorhinolaryngologists in analysing various anatomical areas with their variations on CT imaging [21]. Probably, lack of objective definition and adequate training for identification of important structures and anatomical variations, could be the underlying basis for this level of disagreement between the observers. The results of this study also highlights the importance of inter-disciplinary consultations and discussions and mandating these clinico-radiological meets in the academic curriculum as well as in clinical practice. One another observation from this study based on low inter observer agreement between inexperienced otorhinolaryngologist and the experienced experts in their respective fields, emphasizes the existing learning curve and the importance of training in radiological aspects particularly CT reporting for residents in otorhinolaryngology, preferrably with a standardised reporting format. The importance of a well structured reporting and surgical planning with adequate training to ensure a smooth learning curve has also been highlighted by Ernst BP et al. [5]. The authors would also opine not to ignore the fact that revised training sessions might be equally needed for both radiologists and otorhinolaryngologists irrespective of their experience.

Strengths and Limitations

The authors acknowledge certain limitations of the study. One can not overlook the possibility of selection bias inherent to the retrospective nature of study, but an attempt was made to minimise it by taking a consecutive sample of CT scans confined to a defined time period. This was further aided by random selection using a computer generated sequence. The radiological findings were not correlated with intra operative findings and hence diagnostic accuracy could not be ensued, but then it gets diluted with the fact that it was not the aim of the current study. A relatively smaller sample size in a single centre study marks another limitation, but again the largest sample consisted of 57 scans in the existing few studies in otorhinolaryngology and our study has a comparable sample size of 50 scans. Apart from the comparable sample size, the current study also contributes to the literature by incorporating a comprehensive pre operative checklist and all axial, coronal as well sagittal planes in analysis, and not just limiting to a single plane.

Conclusion

The present study demonstrated a considerable inter observer variability among radiologist and otorhinolaryngologists, irrespective of experience. A few critically important structures which showed an unsatisfactory level of agreement and thus need to be sought after with more training and practice, were also identified. These included Keros type, optic nerve’s location, dehiscence of anterior ethmoid artery, vidian and maxillary nerves, lamina papyracia defect, sphenoid sinus pneumatization and attachment of uncinate process. The study also emphasized the importance of inter disciplinary conferences for pre operative evaluation of sinus CT scans of CRS patients.

Checklist

S.N		Scan check	Right	Interpretation	Left
1	Nasal septum	Deviation		±
		Pneumatization		±
2	Inferior turbinate	Hypertrophy		±
3	Uncinate Process—superior attachment	Landsber and Friedman classification		Type 1—6
4	Middle turbinate	Pneumatization		±
		Interlamellar cell of Grunwald		±
		Paradoxically bent		±
		Turbinate sinus		±
		Missed basal/ground lamella		±
5	Anterior ethmoid cells	Frontal cell		Type 1—4
		Supra orbital cell		±
		Infra orbital cell—Haller cell		±
6	Olfactory fossa	Keros classification		Type 1–3
7	Anterior ethmoid artery	Dehiscence		±
8	Lamina papyracea	Dehiscence		±
9	Maxillary sinus	Septations		±
		Accessory ostia		±
		Dehiscent Infra orbital nerve		±
10	Sphenoid sinus	Pneumatization		Type 1–3
		Maxillary nerve Dehiscence		±
		Vidian nerve Dehiscence		±
11	Optic nerve	DeLano classification		Type 1–4
12	Frontal sinus	Lund-Mackay staging		0–2
13	Maxillary sinus	Lund-Mackay staging		0–2
14	Anterior ethmoid sinus	Lund-Mackay staging		0–2
15	Posterior ethmoid sinus	Lund-Mackay staging		0–2
16	Sphenoid sinus	Lund-Mackay staging		0–2
17	Osteomeatal complex	Lund-Mackay staging		0–2

Authors’ contributions

Conceptualization: PT; Methodology: PT; Formal analysis and investigation: VG, MS; Data analysis, Interpretation, Original draft preparation: PT; Writing—review and editing: PT, SK.

Funding

This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors.

Data availability

The datasets generated during and/or analysed during the current study are available from the corresponding author on reasonable request.

Declarations

Conflict of interests

The authors declare that they have no conflict of interest.

Ethics Approval

Approval by Institutional Ethical Committee was obtained.

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards.

Consent for Publication

Not Applicable, No identifying information submitted in the article. The Manuscript submitted does not contain information about medical device(s)/drug(s). Copy righted material has been used in the manuscript after obtaining adequate permission.