Abstract
BACKGROUND:
Controlled maxillary canine distalization is biomechanically challenging due to the long root and proximity to the buccal cortical plate. Although frictionless T-loop mechanics are widely used, clinical evidence focusing on Blue Elgiloy alloys assessed with three-dimensional imaging remains limited.
METHODS:
This prospective study included 20 patients contributing 61 maxillary canines. Canine distalization was performed using frictionless Blue Elgiloy T-loop mechanics with miniscrew anchorage. The primary outcome was assessed by measuring the R3–miniscrew distance at baseline (T0), 6 weeks (T1), 12 weeks (T2), and 18 weeks (T3). Secondary outcomes, including canine root length, alveolar bone height, root–buccal cortex distance, and buccolingual inclination, were evaluated using cone-beam computed tomography (CBCT) at T0 and T3.
RESULTS:
A significant and progressive reduction in the R3–miniscrew distance was observed over 18 weeks (all P < 0.001), with a mean cumulative distalization of 4.03 ± 0.68 mm. CBCT analysis demonstrated small but statistically significant changes in root length, alveolar bone height, root–buccal cortex distance, and buccolingual inclination, all within clinically acceptable limits. Canines on the preferred chewing side exhibited significantly greater distalization than those on the nonpreferred side (P < 0.001).
CONCLUSIONS:
Blue Elgiloy T-loop mechanics achieved effective and progressive maxillary canine distalization with satisfactory three-dimensional control. Chewing preference was significantly associated with distalization efficiency (ΔR3), highlighting the potential influence of functional factors on orthodontic tooth movement.
Keywords: Blue Elgiloy, chewing preference, cone-beam computed tomography, maxillary canine distalization, T-loop mechanics
Introduction
Canine distalization is a critical step in orthodontic treatment plans involving premolar extraction, particularly for the correction of anterior crowding and dentoalveolar protrusion. However, achieving predictable and controlled canine distalization remains biomechanically challenging due to its long root, large root surface area, and close proximity to the buccal cortical plate. Uncontrolled tipping, excessive torque loss, and undesirable interactions with the surrounding alveolar bone are common concerns during canine retraction.[1,2]
To overcome these challenges, frictionless mechanics have been widely advocated. Among them, the T-loop is a well-established appliance capable of delivering a favorable moment-to-force ratio, allowing for controlled tooth movement with improved root control compared with sliding mechanics. Traditionally, T-loops are fabricated from beta-titanium (TMA) wires because of their elastic properties and ease of activation. Nevertheless, alternative alloys such as Blue Elgiloy (cobalt–chromium) offer practical advantages, including superior formability, heat-treatable stiffness, and lower cost. Despite these advantages, clinical evidence evaluating the biomechanical effectiveness of Blue Elgiloy T-loops remains limited.[3,4,5]
Recent advances in cone-beam computed tomography (CBCT) have enabled precise three-dimensional assessment of orthodontic tooth movement and its effects on surrounding hard tissues. CBCT allows quantitative evaluation of root position, alveolar bone morphology, and tooth inclination, providing insights that are not achievable with conventional two-dimensional imaging. However, few longitudinal studies have applied CBCT to assess the combined effects of canine distalization mechanics on tooth movement, root integrity, and alveolar bone response. In addition to appliance design, functional factors such as chewing preference may influence orthodontic tooth movement. Occlusal loading and masticatory habits can affect periodontal ligament stimulation and bone remodeling, yet their role in the efficiency of canine distalization has not been sufficiently explored.[6,7,8,9,10]
Therefore, the study aimed to (1) assess the magnitude and progression of canine distalization, (2) analyze CBCT-based changes in root length, alveolar bone height, root–cortex relationships, and buccolingual inclination, and (3) investigate the association between preferred chewing side and distalization efficiency (ΔR3). The findings of this study can provide clinically relevant evidence regarding the biomechanical performance and safety of Blue Elgiloy T-loop mechanics.
Materials and Methods
Study design and setting
This study was designed as a prospective study evaluating maxillary canine distalization using frictionless T-loop mechanics fabricated from Blue Elgiloy wire between January 2024 and June 2025 during routine orthodontic care. Each participant was followed for a fixed observation period of 18 weeks, corresponding to the active canine distalization phase. Clinical measurements were obtained at baseline (T0) and at 6-week intervals (T1, T2, and T3). CBCT imaging was performed at T0 and T3 to evaluate three-dimensional positional and hard-tissue changes. All clinical and imaging procedures were standardized and performed within the same clinical setting.
Participants
Patients undergoing fixed orthodontic treatment and requiring canine distalization as part of a premolar extraction protocol were consecutively recruited.
Inclusion criteria
Indication for maxillary canine distalization as part of orthodontic treatment
Fully erupted permanent canines with complete root formation
Absence of systemic diseases or medications affecting bone metabolism
Availability of CBCT images at baseline and follow-up.
Exclusion criteria
Impacted, ankylosed, or previously endodontically treated canines
Craniofacial anomalies or history of orthodontic treatment
Use of medications known to affect bone remodeling
Poor-quality CBCT images unsuitable for quantitative analysis.
Orthodontic procedure
All patients were treated with fixed appliances using a 0.018-inch slot preadjusted edgewise system. Initial leveling and alignment were completed using a standardized archwire sequence until passive engagement of rectangular working wires was achieved. Premolar extraction was performed according to individualized treatment plans before initiating canine distalization.
To provide absolute anchorage, a temporary anchorage device (miniscrew) was placed in the posterior maxillary alveolar bone, typically between the second premolar and first molar, under local anesthesia and aseptic conditions. Miniscrew stability was clinically verified prior to loading.
Canine distalization was carried out using frictionless T-loop mechanics fabricated from 0.017 × 0.025-inch Blue Elgiloy wire. Each T-loop was individually fabricated and preactivated extraorally (200 gr) with a 40° tip-back bend and 60° activation, in accordance with established biomechanical principles, to optimize the moment-to-force ratio and achieve controlled canine distalization while minimizing unwanted rotation. Activation followed a standardized protocol designed to deliver light, continuous orthodontic force appropriate for canine distalization.
The T-loops were activated at baseline (T0) and reactivated at 6-week intervals (T1 and T2) while maintaining consistent loop geometry. The total active distalization period was 18 weeks (T3). No auxiliary mechanics, interarch elastics, or additional anchorage reinforcement were used during the observation period. Miniscrew stability and appliance integrity were monitored throughout treatment, and no failures requiring protocol modification were recorded [Figure 1].
Figure 1.
Clinical application of the Blue Elgiloy T-loop for maxillary canine distalization. Intraoral view of the Blue Elgiloy T-loop used for frictionless maxillary canine distalization, activated between the canine and posterior miniscrew anchorage
CBCT imaging protocol
Cone-beam computed tomography (CBCT) scans were obtained at baseline (T0) and after completion of the distalization phase at 18 weeks (T3). All scans were acquired using the same CBCT unit and identical imaging parameters for all participants to ensure consistency and comparability. The CBCT scans were acquired using the following standardized parameters: voxel size of 0.2 mm, tube voltage of 90 kVp, tube current of 10 mA, and a field of view sufficient to include the maxillary canine region.
Patients were positioned according to the manufacturer’s standard protocol, with the Frankfort horizontal plane parallel to the floor and teeth in maximum intercuspation during image acquisition. The field of view was selected to fully capture the maxillary canine region and surrounding alveolar structures while minimizing radiation exposure, in accordance with the ALARA principle.
CBCT data were reconstructed using a uniform voxel size and exported in Digital Imaging and Communications in Medicine (DICOM) format. All measurements were performed using dedicated CBCT analysis software in multiplanar reconstruction (axial, sagittal, and coronal views). To standardize measurements, head orientation was re-established digitally using anatomical reference planes. The long axis of the canine was identified in three dimensions, and measurements were conducted perpendicular or parallel to this axis as appropriate.
The following CBCT parameters were assessed at T0 and T3:
Canine root length, measured from the cementoenamel junction to the root apex
Alveolar bone height, defined as the vertical distance from the alveolar crest to the reference occlusal plane
Distance from the canine root to the buccal cortical plate, measured at three levels: crestal, midroot, and apical
Buccolingual inclination of the canine, defined as the angle between the long axis of the canine and the reference plane
All CBCT measurements were performed by a single calibrated examiner who was blinded to the timepoint.
Outcome measures
Primary outcomes
The primary outcome was defined as maxillary canine distalization, quantified as the reduction in the linear distance between the canine reference point (R3) and the miniscrew anchorage (R3–miniscrew distance). The reference point was identified clinically as the midpoint of the labial surface of the canine crown at the level of the bracket slot, using direct visualization and a calibrated digital caliper to ensure consistent positioning across all timepoints.
This measurement was used consistently throughout the study to represent canine distalization. The R3–miniscrew distance was recorded at baseline (T0), 6 weeks (T1), 12 weeks (T2), and 18 weeks (T3), and a decrease in this distance indicated canine distalization.
Distalization efficiency was calculated as:
ΔR3 = (R3 – miniscrew distance)T0 - (R3 – miniscrew distance)T3
Secondary outcomes
Secondary outcomes were assessed using CBCT to evaluate three-dimensional positional changes of the canine and surrounding alveolar structures. All CBCT measurements were performed at baseline (T0) and after completion of the distalization phase (T3).
Prior to measurement, CBCT datasets were reoriented digitally to standardize head position. The Frankfort horizontal plane was aligned parallel to the horizontal reference, and the midsagittal plane was aligned vertically. Measurements were performed using multiplanar reconstruction views (axial, sagittal, and coronal) to ensure accurate three-dimensional assessment.
Canine Root Length: Canine root length was defined as the linear distance from the cementoenamel junction (CEJ) to the root apex along the long axis of the canine. The long axis of the canine was identified on sagittal CBCT slices. The CEJ was located as the midpoint between the buccal and palatal enamel–cementum junctions. The distance from this point to the most apical point of the root was measured parallel to the long axis of the tooth.
Alveolar Bone Height: Alveolar bone height was defined as the vertical distance from the alveolar crest adjacent to the canine to a standardized occlusal reference plane. The occlusal reference plane was constructed using stable posterior dental landmarks. On sagittal CBCT images, the most coronal point of the alveolar crest on the buccal aspect of the canine was identified. The perpendicular distance from this point to the occlusal plane was measured. A decrease in alveolar bone height value indicates apical displacement of the alveolar crest relative to the occlusal plane.
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Distance from Canine Root to Buccal Cortical Plate: This parameter was defined as the shortest linear distance between the outer surface of the canine root and the inner surface of the buccal cortical plate. On coronal CBCT slices perpendicular to the long axis of the canine, the shortest distance from the root surface to the buccal cortical plate was measured at each level. Positive changes indicate increased separation between the root and cortical bone.
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Measurement levels
Measurements were obtained at three standardized levels along the root:
Crestal level: approximately 2 mm apical to the CEJ
Midroot level: midpoint between the CEJ and the root apex
Apical level: approximately 2 mm coronal to the root apex
Buccolingual Inclination of the Canine: Buccolingual inclination was defined as the angle between the long axis of the canine and the reference plane. The long axis of the canine was identified by connecting the midpoint of the CEJ to the root apex. The angle between this axis and the predefined reference plane was measured on coronal CBCT images. An increase in angle value indicates buccal tipping of the canine.
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Assessment of chewing preference
Chewing preference was assessed using a structured patient questionnaire combined with clinical observation. Patients were asked to indicate their habitual chewing side, which was confirmed during mastication of a standardized test food. Preference was recorded at baseline and reconfirmed at follow-up visits to ensure consistency.
Sample size calculation
Sample size estimation was based on the primary outcome (change in R3–miniscrew distance from T0 to T3). Using a paired-comparison framework with a two-sided significance level of 0.05 and 80% power, the standard deviation of the paired difference (σ = 0.677 mm) was derived from the dataset. Assuming a conservative clinically meaningful difference of 1.0 mm, the minimum required sample size was estimated at four canines. To improve precision, account for clustering of multiple canines within patients, and enable secondary and exploratory analyses, a larger sample was included. Ultimately, 61 canines from 20 patients were analyzed.
Statistical analysis
Assumptions of normality (Shapiro–Wilk test) and sphericity (Mauchly’s test) were assessed prior to repeated-measures analysis of variance. Changes in the primary outcome over time were analyzed using repeated-measures analysis of variance, with post hoc pairwise comparisons adjusted using the Holm method. CBCT-based secondary outcomes were analyzed using paired t-tests or Wilcoxon signed-rank tests, as appropriate. The association between distalization efficiency (ΔR3) and preferred chewing side was evaluated using a linear mixed-effects model with patient identification included as a random intercept. Effect estimates were reported with 95% confidence intervals, and all statistical tests were two-sided with a significance level of P < 0.05.
To assess intraexaminer reliability, 20% of the CBCT datasets were randomly selected and remeasured after a 2-week interval. Intraclass correlation coefficients (ICC) were calculated for all CBCT-based linear and angular measurements, including root length, alveolar bone height, root–cortex distances, and buccolingual inclination, demonstrating excellent reliability (ICC range: 0.87–0.96).
Results
Baseline characteristics of the canines
At baseline (T0), the canines demonstrated relatively homogeneous anatomical and positional characteristics suitable for distalization [Table 1]. The mean distance between the canine (R3) and the miniscrew anchorage was 19.91 ± 2.34 mm, indicating adequate available space for posterior movement prior to activation of the T-loop.
Table 1.
Baseline canine characteristics (T0)
| R3–miniscrew distance (mm) | 19.91±2.34 |
| Canine root length (mm) | 24.87±1.78 |
| Alveolar bone height (mm) | 14.24±1.49 |
| Buccolingual inclination (°) | 97.35±2.16 |
| Root–buccal cortex distance (crest, mm) | 1.07±0.36 |
| Root–buccal cortex distance (midroot, mm) | 0.62±0.33 |
| Root–buccal cortex distance (apex, mm) | 0.99±0.60 |
Data were presented as mean±SD. CBCT measurements obtained at baseline (T0)
CBCT assessment showed a mean canine root length of 24.87 ± 1.78 mm and a mean alveolar bone height of 14.24 ± 1.49 mm. The spatial relationship between the canine root and the buccal cortical plate revealed a mean root–cortex distance of 1.07 ± 0.36 mm at the crestal level, 0.62 ± 0.33 mm at the midroot level, and 0.99 ± 0.60 mm at the apical level. These measurements indicate close proximity of the canine root to the buccal cortex, particularly at the midroot level, underscoring the biomechanical challenge of controlled distalization.
The mean buccolingual inclination of the canines at baseline was 97.35 ± 2.16°, reflecting a near-upright orientation relative to the reference plane. No clinically relevant asymmetry in baseline measurements was observed between left and right canines [Table 1].
Overall, the baseline CBCT findings demonstrate that the canines were positioned within a constrained alveolar envelope but without extreme angulation or bone deficiency, providing an appropriate anatomical foundation for evaluating the magnitude and safety of canine distalization using Blue Elgiloy T-loop mechanics, the clinical progress of the canine distalization was showed in Figure 2.
Figure 2.
The clinical progress of canine distalization. (a and b) T0, (c and d) T1, (e and f) T2, (g and h) T3
Progression of canine distalization
A significant and progressive distalization efficiency (ΔR3) was observed throughout the observation period. The mean distance decreased from 19.91 ± 2.34 mm at baseline (T0) to 18.79 ± 2.25 mm at 6 weeks (T1), 17.27 ± 2.23 mm at 12 weeks (T2), and 15.89 ± 2.23 mm at 18 weeks (T3), with all comparisons relative to baseline showing statistical significance (all P < 0.001). The mean cumulative distalization achieved over 18 weeks was 4.03 ± 0.68 mm, reflecting continuous and clinically meaningful canine distalization. Percentage changes ranged from −2.45% for root length to + 54.55% for apical root–cortex distance, indicating modest structural changes alongside substantial spatial repositioning of the canine [Figure 3].
Figure 3.
Progression of canine distalization over time. The figure illustrated the progressive reduction in the distance between the maxillary canine (R3) and the miniscrew anchorage from baseline (T0) to 6 weeks (T1), 12 weeks (T2), and 18 weeks (T3). Values are presented as mean ± standard deviation. A significant decrease in the R3–miniscrew distance was observed at all follow-up time points compared with baseline (all P < 0.001), indicating continuous and clinically meaningful canine distalization during the 18-week period
CBCT-based structural and positional changes
CBCT evaluation revealed statistically significant changes in several secondary outcomes between T0 and T3. Mean canine root length decreased by 0.61 mm (95% CI: −0.75 to −0.48; P < 0.001), while alveolar bone height decreased by 0.88 mm (95% CI: −1.02 to −0.74; P < 0.001).
Distances from the canine root to the buccal cortical plate increased significantly at all three measurement levels. The mean increase was 0.44 mm at the crestal level, 0.18 mm at the midroot level, and 0.54 mm at the apical level, with all P < 0.001. Buccolingual inclination also increased significantly from 97.35 ± 2.16° to 101.90 ± 3.43°, corresponding to a mean change of 4.55° (95% CI: 3.60–5.50; P < 0.001) [Table 2].
Table 2.
CBCT changes from baseline to 18 weeks (T0 vs T3)
| T0 | T3 | Δ Mean (95% CI) | % Change | P | |
|---|---|---|---|---|---|
| Canine root length (mm) | 24.87±1.78 | 24.26±1.79 | −0.61 (−0.75 to −0.48) | −2.45% | <0.001 |
| Alveolar bone height (mm) | 14.24±1.49 | 13.36±1.49 | −0.88 (−1.02 to −0.74) | −6.18% | <0.001 |
| Root–cortex distance (crest, mm) | 1.07±0.36 | 1.51±0.72 | +0.44 (0.27 to 0.61) | +41.12% | <0.001 |
| Root–cortex distance (midroot, mm) | 0.62±0.33 | 0.80±0.43 | +0.18 (0.09 to 0.27) | +29.03% | <0.001 |
| Root–cortex distance (apex, mm) | 0.99±0.60 | 1.53±0.88 | +0.54 (0.37 to 0.71) | +54.55% | <0.001 |
| Buccolingual inclination (°) | 97.35±2.16 | 101.90±3.43 | +4.55 (3.60 to 5.50) | +4.67% | <0.001 |
Data were presented as mean±standard deviation (n = 61 canines). % change was calculated as (ΔMean/T0) × 100. Statistical significance was assessed using repeated-measures analysis of variance with Holm-adjusted post hoc comparisons
Association between chewing preference and distalization efficiency (ΔR3)
Distalization efficiency (ΔR3) differed according to chewing-side concordance. In the linear mixed-effects model accounting for clustering of teeth within patients, canines located on the preferred chewing side exhibited significantly greater distalization than those on the nonpreferred side (4.35 ± 0.59 mm vs. 3.66 ± 0.64 mm). The estimated effect size for chewing-side concordance was β = 0.69 mm (95% CI: 0.38–1.00; P < 0.001). Sensitivity analyses using nonparametric testing yielded consistent results.
Discussion
The study evaluated the effectiveness and three- dimensional effects of maxillary canine distalization using Blue Elgiloy T-loop mechanics over an 18-week period. The results demonstrated that this approach produced progressive, statistically significant, and clinically meaningful canine distalization, accompanied by quantifiable CBCT-based changes in root position, alveolar bone morphology, and buccolingual inclination. In addition, distalization efficiency (ΔR3) was significantly associated with functional chewing preference, a factor that has received limited attention in previous orthodontic literature.
The primary outcome revealed a mean cumulative canine distalization of 4.03 ± 0.68 mm over 18 weeks, corresponding to an average rate of approximately 0.22 mm per week. This rate is consistent with values reported for frictionless mechanics using T-loops fabricated from beta-titanium (TMA), where distalization rates typically range from 0.18 to 0.30 mm per week. These findings suggest that, when appropriately designed and activated, Blue Elgiloy T-loops are biomechanically comparable to TMA-based systems in terms of efficiency and force delivery.[11]
In contrast, studies employing sliding mechanics with elastomeric chains or nickel–titanium coil springs have reported greater variability in canine movement and a higher tendency toward uncontrolled tipping due to frictional resistance. The linear and continuous distalization efficiency (ΔR3) observed in the present study supports the theoretical advantages of frictionless mechanics and confirms the clinical reliability of Blue Elgiloy T-loops across repeated activation intervals.[12,13]
CBCT analysis demonstrated a statistically significant reduction in canine root length (−0.61 mm) after 18 weeks. Although statistically significant, this magnitude of change falls within the range reported in CBCT-based studies of canine retraction using both frictionless and sliding mechanics, where mean root length reductions between 0.3 and 1.0 mm have been described over similar observation periods. Importantly, the degree of change observed in this study does not exceed commonly accepted thresholds for clinically relevant external apical root resorption and may reflect physiological remodeling associated with orthodontic tooth movement.[14,15]
A modest but significant reduction in alveolar bone height (−0.88 mm) was also observed. Previous CBCT studies have reported comparable vertical changes in alveolar bone height during extraction-based orthodontic treatment, particularly in the canine region. These changes are generally interpreted as adaptive bone remodeling rather than pathological bone loss, and the present findings are consistent with this interpretation.[16]
Notably, the distances between the canine root and the buccal cortical plate increased significantly at the crestal, midroot, and apical levels. This finding contrasts with some CBCT investigations of canine retraction using sliding mechanics, which have reported reduced root–cortex distances and an increased risk of cortical contact. The increase observed in the present study suggests that distalization occurred within the alveolar envelope, supporting the concept that frictionless mechanics with a favorable moment-to-force ratio may better preserve root–bone relationships.[17]
The observed increase in buccolingual inclination (+4.55°) indicates a degree of buccal tipping during distalization. Similar magnitudes of angular change have been reported in CBCT studies evaluating canine retraction with T-loop mechanics. While statistically significant, the magnitude of inclination change remained within clinically acceptable limits and did not compromise root proximity to the buccal cortex. This underscores the importance of careful loop design and activation, particularly when using cobalt–chromium alloys with higher stiffness than TMA.[13]
An important and novel finding of this study is the significant association between preferred chewing side and distalization efficiency (ΔR3). Canines located on the preferred chewing side exhibited, on average, 0.69 mm greater canine distalization than those on the nonpreferred side, even after accounting for clustering of multiple canines within individual patients using a linear mixed-effects model. While most orthodontic studies assume symmetrical biological responses to applied forces, emerging evidence from craniofacial biology suggests that masticatory function can influence periodontal ligament stimulation and regional bone remodeling. The present findings provide clinical support for this concept and may partially explain asymmetrical canine movement occasionally observed in clinical practice despite the use of identical bilateral mechanics. Further investigations are needed to clarify the biological mechanisms underlying this association and its potential implications for individualized orthodontic treatment planning.
From a clinical perspective, Blue Elgiloy offers several practical advantages, including good formability, heat-treatable stiffness, and lower cost compared with TMA. The present findings indicate that these practical benefits do not compromise biomechanical performance. On the contrary, Blue Elgiloy T-loops provided predictable distalization and acceptable short-term hard-tissue responses, supporting their use as a cost-effective and clinically reliable alternative in routine orthodontic practice, particularly in resource-limited settings.
The study had some limitations. First, the absence of a control group precludes direct comparison with other wire alloys or mechanics. Second, the observation period was limited to 18 weeks, and long-term effects on root integrity and alveolar bone morphology were not assessed. Third, CBCT imaging was limited to two timepoints (T0 and T3) in accordance with the ALARA principle, which may have precluded detection of intermediate changes. Future randomized controlled trials comparing Blue Elgiloy and TMA T-loops, as well as studies with longer follow-up periods, are warranted. Further research exploring the biological basis of functional laterality in orthodontic tooth movement would also be of considerable interest.
Conclusion
Canine distalization using Blue Elgiloy T-loop mechanics produced progressive and clinically meaningful canine distalization over an 18-week period. Quantitative CBCT analysis demonstrated measurable but acceptable changes in canine root length, alveolar bone height, root–cortex relationships, and buccolingual inclination, indicating satisfactory three-dimensional control during distalization. In addition, distalization efficiency (ΔR3) was significantly greater for canines located on the preferred chewing side, suggesting that functional factors may influence orthodontic tooth movement. These findings further support the use of Blue Elgiloy as a cost-effective, formable, and clinically reliable alternative to TMA for routine orthodontic practice.
Data availability statement
The data presented in this study are available upon reasonable request, after the signature of a formal data-sharing agreement in an anonymous form, from the corresponding author because they are protected by privacy.
Author contributions
Conceptualization, P.T.H.T.; methodology, P.T.H.T.; software, H.V.; validation, P.T.T. and H.V.; formal analysis, investigation, P.T.H.T.; resources, H.V.; data curation, N.T.H.; writing—original draft preparation, H.V.; writing—review and editing, T.M.H.; visualization, P.T.H.T.; supervision, D.T.M.H.; project administration, T.M.H., N.T.H.; funding acquisition, D.T.M.T., N.T.H. All authors have read and agreed to the published version of the manuscript.
Institutional Review Board Statement
Institutional Review Board of Hai Phong University of Medicine and Pharmacy (No. 191/QD-YDHP).
Informed consent statement
Informed consent was obtained from all subjects involved in this study.
Conflicts of interest
There are no conflicts of interest.
Funding Statement
Nil.
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Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.
Data Availability Statement
The data presented in this study are available upon reasonable request, after the signature of a formal data-sharing agreement in an anonymous form, from the corresponding author because they are protected by privacy.