| Literature DB >> 34884346 |
Yu-Chuan Tseng1,2, Shih-Wei Liang1, Szu-Ting Chou1,2, Shih-Chieh Chen2, Chin-Yun Pan2, Chun-Ming Chen1,3.
Abstract
This study investigated the relationship between the thickness of the ramus and skeletal patterns using cone-beam computed tomography (CBCT) for sagittal split ramus osteotomy. Ninety participants were categorized into three skeletal patterns (Class I, Class II, and Class III). The first vertical slice (slice 0) was observed in the intact mandibular canal, and then moved forward to 40 mm (slice 21) with a 2 mm interval. The thickness of buccal bone marrow (B value) was measured. A B value of ≤0.8 mm was considered to be the major risk factor causing the occurrence of postoperative lower lip paresthesia. There were 461 sides with a B value of ≤0.8 mm. There was a significant difference in the skeletal patterns [Class III (198 sides: 15.7%) > Class I (159 sides: 12.6%) > Class II (104 sides: 8.3%)]. Class II participants had significantly larger B values (2.14 to 3.76 mm) and a lower occurrence rate (≤0.8 mm) than those of Class III participants (1.5 to 3 mm) in front of the mandibular foramen (from 6 mm to 20 mm). Class III participants had significantly shorter buccal bone marrow distance and a higher occurrence rate of B values (≤0.8 mm) than Class II.Entities:
Keywords: buccal bone marrow distance; cone-beam computed tomography; mandibular canal; sagittal split ramus osteotomy
Year: 2021 PMID: 34884346 PMCID: PMC8658161 DOI: 10.3390/jcm10235644
Source DB: PubMed Journal: J Clin Med ISSN: 2077-0383 Impact factor: 4.241
Figure 1Green circle: mandibular canal (base slice: 0 mm); twenty-one vertical slices (red lines) from 0 mm forward to 40 mm.
Figure 2Red line distance (H: thickness of mandible). A: buccal cortical bone thickness; B: buccal cortical bone marrow thickness; C: lingual bone marrow thickness; D: lingual cortical bone thickness.
The summary of participants’ characteristics. (n = 90).
| Total Participant by Gender: 60 Female and 30 Male |
|---|
| Total participant by skeletal pattern: |
| 30 Class I (21 female; 9 male) |
| 30 Class II (24 female; 6 male) |
| 30 Class III (15 female; 15 male) |
| Participants with buccal bone marrow distance ≤ 0.8 mm |
| by gender (%): 45 female (75%); 18 male (60%) |
| by skeletal pattern (%): |
| Class I (17 female, 81%; 4 male, 44%) |
| Class II (16 female, 67%; 4 male, 67%) |
| Class III (12 female, 73%; 10 male, 67%) |
n: Number of participants.
From the base plane (0 mm) to 40 mm forward, the thickness (mm, mean ± SD) of buccal cortical bone and marrow with their skeletal patterns in the One-way ANOVA with post hoc Tukey HSD test.
| Variables | A | B | A + B | ||||
|---|---|---|---|---|---|---|---|
| (Mean ± SD, mm) | (Mean ± SD, mm) | (Mean ± SD, mm) | |||||
| 0 mm | Class I | 2.47 ± 0.58 | 0.415 | 2.29 ± 1.42 | 0.252 | 4.75 ± 1.43 | 0.129 |
| Class II | 2.61 ± 0.68 | 2.35 ± 1.38 | 4.96 ± 1.28 | ||||
| Class III | 2.50 ± 0.61 | 1.97 ± 1.17 | 4.47 ± 1.21 | ||||
| 2 mm | Class I | 2.62 ± 0.46 | 0.512 | 2.12 ± 1.38 | 0.297 | 4.73 ± 1.43 | 0.201 |
| Class II | 2.73 ± 0.66 | 2.19 ± 1.28 | 4.92 ± 1.25 | ||||
| Class III | 2.65 ± 0.51 | 1.85 ± 1.14 | 4.50 ± 1.17 | ||||
| 4 mm | Class I | 2.62 ± 0.62 | 0.56 | 1.78 ± 1.44 | 0.28 | 4.39 ± 1.44 | 0.115 |
| Class II | 2.71 ± 0.73 | 2.11 ± 1.28 | 4.82 ± 1.31 | ||||
| Class III | 2.57 ± 0.69 | 1.76 ± 1.33 | 4.34 ± 1.36 | ||||
| 6 mm | Class I | 2.54 ± 0.53 | 0.339 | 1.72 ± 1.29 | 0.019 * | 4.26 ± 1.41 | 0.007 * |
| Class II | 2.66 ± 0.60 | 2.14 ± 1.21 | Class II > III | 4.81 ± 1.35 | Class II > III | ||
| Class III | 2.52 ± 0.55 | 1.50 ± 1.27 | 4.02 ± 1.37 | ||||
| 8 mm | Class I | 2.85 ± 0.70 | 0.131 | 1.77 ± 1.40 | 0.003 * | 4.61 ± 1.45 | <0.001 * |
| Class II | 2.96 ± 0.70 | 2.44 ± 1.31 | Class II > I | 5.39 ± 1.45 | Class II > I | ||
| Class III | 2.70 ± 0.71 | 1.63 ± 1.43 | Class II > III | 4.33 ± 1.49 | Class II > III | ||
| 10 mm | Class I | 2.90 ± 0.53 | 0.022 * | 1.73 ± 1.37 | 0.001 * | 4.62 ± 1.51 | <0.001 * |
| Class II | 3.02 ± 0.54 | Class II > III | 2.56 ± 1.32 | Class II > I | 5.58 ± 1.49 | Class II > I | |
| Class III | 2.71 ± 0.74 | 1.68 ± 1.42 | Class II > III | 4.39 ± 1.66 | Class II > III | ||
| 12 mm | Class I | 3.10 ± 0.70 | 0.455 | 2.08 ± 1.54 | <0.001 * | 5.18 ± 1.64 | <0.001 * |
| Class II | 3.08 ± 0.67 | 3.11 ± 1.39 | Class II > I | 6.19 ± 1.49 | Class II > I | ||
| Class III | 2.94 ± 0.81 | 1.83 ± 1.60 | Class II > III | 4.78 ± 1.77 | Class II > III | ||
| 14 mm | Class I | 3.12 ± 0.64 | 0.052 | 2.36 ± 1.59 | <0.001 * | 5.48 ± 1.59 | <0.001 * |
| Class II | 3.12 ± 0.62 | 3.26 ± 1.38 | Class II > I | 6.32 ± 1.32 | Class II > I | ||
| Class III | 2.87 ± 0.63 | 2.20 ± 1.65 | Class II > III | 5.07 ± 1.94 | Class II > III | ||
| 16 mm | Class I | 3.11 ± 0.64 | 0.814 | 2.99 ± 1.71 | 0.001 * | 6.1 ± 1.72 | <0.001 * |
| Class II | 3.15 ± 0.71 | 3.64 ± 1.41 | Class II > III | 6.79 ± 1.34 | Class II > III | ||
| Class III | 3.06 ± 0.81 | 2.52 ± 1.73 | 5.58 ± 1.90 | ||||
| 18 mm | Class I | 3.22 ± 0.74 | 0.195 | 2.92 ± 1.59 | 0.006 * | 6.14 ± 1.65 | 0.006 * |
| Class II | 3.08 ± 0.58 | 3.64 ± 1.33 | Class II > III | 6.72 ± 1.28 | Class II > III | ||
| Class III | 3.01 ± 0.66 | 2.70 ± 1.99 | 5.71 ± 2.09 | ||||
| 20 mm | Class I | 3.17 ± 0.71 | 0.584 | 3.29 ± 1.42 | 0.026 * | 6.46 ± 1.56 | 0.114 |
| Class II | 3.08 ± 0.62 | 3.76 ± 1.30 | Class II > III | 6.83 ± 1.32 | |||
| Class III | 3.20 ± 0.74 | 3.00 ± 1.81 | 6.20 ± 2.02 | ||||
| 22 mm | Class I | 3.07 ± 0.68 | 0.456 | 3.07 ± 1.55 | 0.328 | 6.14 ± 1.58 | 0.157 |
| Class II | 3.21 ± 0.59 | 3.43 ± 1.20 | 6.63 ± 1.27 | ||||
| Class III | 3.09 ± 0.68 | 3.05 ± 1.84 | 6.14 ± 1.94 | ||||
| 24 mm | Class I | 3.14 ± 0.66 | 0.540 | 3.55 ± 1.46 | 0.600 | 6.69 ± 1.61 | 0.737 |
| Class II | 3.01 ± 0.64 | 3.63 ± 1.20 | 6.64 ± 1.13 | ||||
| Class III | 3.11 ± 0.67 | 3.36 ± 1.73 | 6.48 ± 1.85 | ||||
| 26 mm | Class I | 3.09 ± 0.79 | 0.984 | 3.18 ± 1.31 | 0.990 | 6.26 ± 1.45 | 0.996 |
| Class II | 3.07 ± 0.46 | 3.20 ± 1.29 | 6.27 ± 1.36 | ||||
| Class III | 3.07 ± 0.56 | 3.21 ± 1.66 | 6.29 ± 1.72 | ||||
| 28 mm | Class I | 3.06 ± 0.71 | 0.492 | 3.41 ± 1.20 | 0.220 | 6.47 ± 1.43 | 0.153 |
| Class II | 2.92 ± 0.60 | 3.11 ± 1.47 | 6.03 ± 1.43 | ||||
| Class III | 2.96 ± 0.71 | 3.57 ± 1.67 | 6.53 ± 1.70 | ||||
| 30 mm | Class I | 3.03 ± 0.72 | 0.295 | 3.19 ± 1.20 | 0.012 * | 6.23 ± 1.32 | 0.087 |
| Class II | 3.08 ± 0.55 | 2.73 ± 1.29 | Class III > II | 5.82 ± 1.39 | |||
| Class III | 2.91 ± 0.52 | 3.44 ± 1.41 | 6.36 ± 1.43 | ||||
| 32 mm | Class I | 3.02 ± 0.70 | 0.587 | 3.13 ± 1.20 | 0.096 | 6.15 ± 1.38 | 0.047 * |
| Class II | 2.89 ± 0.60 | 2.80 ± 1.62 | 5.70 ± 1.55 | Class III > II | |||
| Class III | 2.97 ± 0.72 | 3.40 ± 1.58 | 6.38 ± 1.54 | ||||
| 34 mm | Class I | 2.89 ± 0.64 | 0.403 | 2.95 ± 1.17 | 0.017 * | 5.84 ± 1.29 | 0.042 * |
| Class II | 3.03 ± 0.59 | 2.41 ± 1.33 | Class III > II | 5.43 ± 1.54 | Class III > II | ||
| Class III | 3.03 ± 0.63 | 3.08 ± 1.35 | 6.11 ± 1.40 | ||||
| 36 mm | Class I | 3.07 ± 0.73 | 0.607 | 2.64 ± 1.21 | 0.005 * | 5.72 ± 1.36 | 0.020 * |
| Class II | 3.00 ± 0.71 | 2.30 ± 1.55 | Class III > II | 5.30 ± 1.59 | Class III > II | ||
| Class III | 2.94 ± 0.75 | 3.17 ± 1.38 | 6.11 ± 1.42 | ||||
| 38 mm | Class I | 2.85 ± 0.52 | 0.166 | 2.41 ± 1.25 | 0.357 | 5.26 ± 1.32 | 0.242 |
| Class II | 3.08 ± 0.60 | 2.27 ± 1.35 | 5.35 ± 1.57 | ||||
| Class III | 3.00 ± 0.62 | 2.67 ± 1.37 | 5.68 ± 1.32 | ||||
| 40 mm | Class I | 3.17 ± 0.77 | 0.073 | 1.98 ± 1.16 | 0.014 * | 5.15 ± 1.37 | 0.122 |
| Class II | 2.77 ± 0.65 | 2.39 ± 1.77 | Class III > I | 5.15 ± 1.70 | |||
| Class III | 2.89 ± 0.81 | 2.77 ± 1.44 | 5.67 ± 1.36 |
A: Buccal cortex of mandibular canal sheath; B: Dimension of mandibular canal. *: Significant, p < 0.05.
Figure 3The mean B value (buccal bone marrow distance) in the three skeletal patterns.
From the base plane (0 mm) to 40 mm forward, the thickness (mm, mean ± SD) of the lingual cortical bone and marrow with their skeletal patterns in the One-way ANOVA with post hoc Tukey HSD test.
| Variables | C | D | H | ||||
|---|---|---|---|---|---|---|---|
| (Mean ± SD, mm) | (Mean ± SD, mm) | (Mean ± SD, mm) | |||||
| 0 mm | Class I | 0.06 ± 0.30 | 0.114 | 1.14 ± 0.57 | 0.195 | 9.79 ± 1.61 | 0.641 |
| Class II | 0.01 ± 0.06 | 0.97 ± 0.52 | 9.55 ± 1.37 | ||||
| Class III | 0.00 ± 0.00 | 1.05 ± 0.43 | 9.65 ± 1.31 | ||||
| 2 mm | Class I | 0.02 ± 0.12 | 0.368 | 1.28 ± 0.65 | 0.448 | 9.96 ± 1.50 | 0.735 |
| Class II | 0.03 ± 0.18 | 1.15 ± 0.56 | 9.79 ± 1.38 | ||||
| Class III | 0.00 ± 0.00 | 1.19 ± 0.46 | 9.78 ± 1.30 | ||||
| 4 mm | Class I | 0.14 ± 0.36 | 0.644 | 1.65 ± 0.71 | 0.580 | 10.08 ± 1.60 | 0.480 |
| Class II | 0.18 ± 0.42 | 1.59 ± 0.50 | 10.21 ± 1.44 | ||||
| Class III | 0.11 ± 0.34 | 1.53 ± 0.71 | 9.89 ± 1.27 | ||||
| 6 mm | Class I | 0.35 ± 0.57 | 0.239 | 1.83 ± 0.71 | 0.077 | 10.25 ± 1.66 | 0.116 |
| Class II | 0.19 ± 0.42 | 1.56 ± 0.60 | 10.38 ± 1.47 | ||||
| Class III | 0.29 ± 0.53 | 1.65 ± 0.65 | 9.84 ± 1.29 | ||||
| 8 mm | Class I | 0.41 ± 0.63 | 0.881 | 2.20 ± 0.96 | 0.004 * | 11.09 ± 1.68 | 0.364 |
| Class II | 0.42 ± 0.71 | 1.74 ± 0.56 | Class I > II | 11.25 ± 1.70 | |||
| Class III | 0.46 ± 0.67 | 2.08 ± 0.75 | Class III > II | 10.84 ± 1.44 | |||
| 10 mm | Class I | 0.64 ± 0.80 | 0.255 | 1.87 ± 0.67 | 0.005 * | 11.19 ± 1.78 | 0.140 |
| Class II | 0.41 ± 0.70 | 1.58 ± 0.56 | Class I > II | 11.42 ± 1.64 | |||
| Class III | 0.51 ± 0.78 | 1.95 ± 0.70 | Class III > II | 10.81 ± 1.65 | |||
| 12 mm | Class I | 0.69 ± 0.87 | 0.165 | 2.23 ± 0.99 | 0.006 * | 12.11 ± 1.90 | 0.515 |
| Class II | 0.42 ± 0.65 | 1.91 ± 0.62 | Class III > II | 12.28 ± 1.80 | |||
| Class III | 0.65 ± 1.01 | 2.37 ± 0.74 | 11.90 ± 1.75 | ||||
| 14 mm | Class I | 0.71 ± 0.86 | 0.027 * | 1.88 ± 0.54 | 0.010 * | 12.12 ± 1.84 | 0.392 |
| Class II | 0.39 ± 0.70 | Class III > II | 1.69 ± 0.56 | Class III > II | 12.15 ± 1.64 | ||
| Class III | 0.83 ± 1.16 | 2.03 ± 0.67 | 11.74 ± 1.89 | ||||
| 16 mm | Class I | 0.56 ± 0.97 | 0.009 * | 2.20 ± 0.72 | 0.005 * | 12.64 ± 1.73 | 0.879 |
| Class II | 0.46 ± 0.77 | Class III > I | 1.92 ± 0.68 | Class III > II | 12.79 ± 1.64 | ||
| Class III | 1.02 ± 1.32 | Class III > II | 2.36 ± 0.82 | 12.76 ± 1.79 | |||
| 18 mm | Class I | 0.64 ± 0.73 | 0.010 * | 1.94 ± 0.51 | 0.305 | 12.61 ± 1.72 | 0.905 |
| Class II | 0.39 ± 0.73 | Class III > II | 1.81 ± 0.67 | Class III > II | 12.66 ± 1.59 | ||
| Class III | 0.91 ± 0.63 | 2.00 ± 0.67 | 12.52 ± 1.99 | ||||
| 20 mm | Class I | 0.42 ± 0.67 | 0.015 * | 2.35 ± 0.64 | 0.003 * | 13.05 ± 1.72 | 0.370 |
| Class II | 0.45 ± 0.71 | Class III > II | 1.95 ± 0.63 | Class I > II | 12.86 ± 1.57 | ||
| Class III | 0.83 ± 1.09 | 2.47 ± 1.17 | Class III > II | 13.33 ± 2.11 | |||
| 22 mm | Class I | 0.64 ± 1.01 | 0.007 * | 2.06 ± 0.58 | 0.654 | 12.68 ± 1.71 | 0.424 |
| Class II | 0.31 ± 0.57 | Class III > II | 2.01 ± 0.61 | 12.51 ± 1.65 | |||
| Class III | 0.90 ± 1.29 | 2.11 ± 0.71 | 12.95 ± 2.12 | ||||
| 24 mm | Class I | 0.35 ± 0.55 | 0.054 | 2.39 ± 0.67 | 0.125 | 13.00 ± 1.77 | 0.084 |
| Class II | 0.33 ± 0.62 | 2.20 ± 0.71 | 12.63 ± 1.55 | ||||
| Class III | 0.59 ± 0.79 | 2.53 ± 1.15 | 13.39 ± 2.20 | ||||
| 26 mm | Class I | 0.30 ± 0.60 | 0.006 * | 2.14 ± 0.63 | 0.990 | 12.49 ± 1.78 | 0.267 |
| Class II | 0.27 ± 0.52 | Class III > I | 2.13 ± 0.68 | 12.31 ± 1.52 | |||
| Class III | 0.71 ± 1.2 | Class III > II | 2.13 ± 0.57 | 12.84 ± 2.07 | |||
| 28 mm | Class I | 0.28 ± 0.46 | 0.087 | 2.42 ± 0.73 | 0.887 | 12.69 ± 1.91 | 0.173 |
| Class II | 0.51 ± 0.88 | 2.35 ± 0.63 | 12.46 ± 1.43 | ||||
| Class III | 0.57 ± 0.87 | 2.37 ± 0.80 | 13.09 ± 2.13 | ||||
| 30 mm | Class I | 0.37 ± 0.52 | 0.195 | 2.09 ± 0.63 | 0.018 * | 12.23 ± 1.78 | 0.909 |
| Class II | 0.58 ± 0.82 | 2.29 ± 0.76 | Class II > III | 12.32 ± 1.46 | |||
| Class III | 0.61 ± 0.94 | 1.93 ± 0.64 | 12.37 ± 1.95 | ||||
| 32 mm | Class I | 0.26 ± 0.46 | 0.001 * | 2.38 ± 0.76 | 0.254 | 12.26 ± 1.90 | 0.614 |
| Class II | 0.87 ± 1.18 | Class II > I | 2.46 ± 0.83 | 12.52 ± 1.67 | |||
| Class III | 0.58 ± 0.88 | 2.22 ± 0.85 | 12.58 ± 2.06 | ||||
| 34 mm | Class I | 0.42 ± 0.61 | 0.001 * | 2.22 ± 0.63 | 0.002 * | 11.98 ± 1.61 | 0.338 |
| Class II | 0.98 ± 1.04 | Class II > I | 2.30 ± 0.63 | Class I > III | 12.39 ± 1.72 | ||
| Class III | 0.52 ± 0.70 | Class II > III | 1.90 ± 0.61 | Class II > III | 11.94 ± 1.92 | ||
| 36 mm | Class I | 0.36 ± 0.56 | <0.001 * | 2.5 ± 0.73 | 0.004 * | 11.99 ± 1.80 | 0.057 |
| Class II | 1.27 ± 1.33 | Class II > I | 2.63 ± 0.95 | Class I > III | 12.85 ± 2.00 | ||
| Class III | 0.37 ± 0.57 | Class II > III | 2.14 ± 0.66 | Class II > III | 12.11 ± 1.96 | ||
| 38 mm | Class I | 0.53 ± 0.66 | 0.002 * | 2.29 ± 0.68 | 0.004 * | 11.57 ± 1.60 | 0.131 |
| Class II | 1.18 ± 1.40 | Class II > I | 2.25 ± 0.88 | Class I > III | 12.44 ± 2.56 | ||
| Class III | 0.49 ± 0.69 | Class II > III | 1.87 ± 0.64 | 11.62 ± 1.94 | |||
| 40 mm | Class I | 0.55 ± 0.72 | 0.084 | 2.54 ± 0.79 | 0.089 | 11.79 ± 1.81 | 0.899 |
| Class II | 1.06 ± 1.42 | 2.26 ± 1.05 | 12.04 ± 2.73 | ||||
| Class III | 0.60 ± 0.79 | 2.21 ± 0.68 | 11.83 ± 1.97 |
C: Lingual bone marrow; D: Lingual cortical bone of mandible; H: Thickness of mandible. *: Significant, p < 0.05.
The summary of the characteristics of a total of 1890 slices (3780 sides).
| Total Sides: Female (2520 Sides); Male (1260 Sides) |
|---|
| Buccal bone marrow distance ≤ 0.8 mm (461 sides): |
| by gender (female > male): female (294 sided); male (167 sides) |
| by skeletal pattern (Class III > Class I > Class II) * |
| Class I (159 sides), Class II (104 sides), Class III (198 sides) |
| Buccal bone marrow distance ≤ 0.8 mm (mean value: mm): |
| by gender (female > male) **: female: 0.33 ± 0.30 mm; male: 0.25 ± 0.29 mm |
| by skeletal pattern (Class II > Class III) *** |
| Class I: 0.31 ± 0.31 mm; Class II: 0.37 ± 0.31 mm; Class III: 0.25 ± 0.27 mm |
*: Significant, p < 0.05 in the Bonferroni post hoc test for chi-square tests. **: Significant, p < 0.05 in the Student’s t-test. ***: Significant, p < 0.05 in the One-way ANOVA with post hoc Tukey HSD test.
From slice 0 (0 mm) to slice 20 (40 mm), the percentage in the buccal bone marrow distance (SBM ≤ 0.8 mm) of skeletal patterns.
| Variables | Class I | Class II | Class III | Significant | |||
|---|---|---|---|---|---|---|---|
| 0 mm | 13.33% | 15.00% | 16.67% | 0.877 | |||
| 2 mm | 18.33% | 15.00% | 18.33% | 0.856 | |||
| 4 mm | 28.33% | 16.67% | 30.00% | 0.185 | |||
| 6 mm | 26.67% | 15.00% | 35.00% | 0.041 * | Class III > II | ||
| 8 mm | 31.67% | 15.00% | 35.00% | 0.031 * | Class I > II, Class III > II | ||
| 10 mm | 31.67% | 10.00% | 30.00% | 0.008 * | Class I > II, Class III > II | ||
| 12 mm | 25.00% | 3.33% | 30.00% | 0.001 * | Class I > II, Class III > II | ||
| 14 mm | 21.67% | 3.33% | 23.33% | 0.004 * | Class I > II, Class III > II | ||
| 16 mm | 11.67% | 1.67% | 15.00% | 0.034 * | Class I > II, Class III > II | ||
| 18 mm | 8.33% | 1.67% | 18.33% | 0.007 * | Class III > II | ||
| 20 mm | 3.33% | 1.67% | 13.33% | 0.016 * | Class III > II | ||
| 22 mm | 3.33% | 1.67% | 15.00% | 0.006 * | |||
| 24 mm | 1.67% | 0.00% | 6.67% | 0.069 | |||
| 26 mm | 1.67% | 1.67% | 5.00% | 0.439 | |||
| 28 mm | 0.00% | 8.33% | 3.33% | 0.059 | |||
| 30 mm | 1.67% | 8.33% | 1.67% | 0.093 | |||
| 32 mm | 1.67% | 11.67% | 3.33% | 0.038 * | Class II > I | ||
| 34 mm | 1.67% | 11.67% | 3.33% | 0.038 * | Class II > I | ||
| 36 mm | 5.00% | 16.67% | 5.00% | 0.035 * | Class II > I, Class II > III | ||
| 38 mm | 11.67% | 6.67% | 10.00% | 0.635 | |||
| 40 mm | 18.33% | 6.67% | 11.67% | 0.147 | |||
*: Significant, p < 0.05 in the Bonferroni post hoc test for chi-square tests.