03 Clinical Results Miks

Author

SUE

Published

April 18, 2024

Modified

July 17, 2024

Packages

Packages for the modeling

Dataset

EDA

Add the clinical data 2

Join

EDA Descriptive Table

Table 1

Descriptive Table
Characteristic 3D Replica, N = 241 Control, N = 221
Sex

    Female 13 (54%) 16 (73%)
    Male 11 (46%) 6 (27%)
Age (surgery) 16.00 (16.00, 17.00) 17.50 (17.00, 19.00)
Total surgery time (min) 45 (40, 51) 60 (50, 70)
Extra- alveolar time (s) 35 (30, 60) 55 (30, 83)
Donor fitting times

    1 15 (63%) 7 (32%)
    2 5 (21%) 8 (36%)
    3 4 (17%) 5 (23%)
    4 0 (0%) 1 (4.5%)
    5 0 (0%) 1 (4.5%)
Moores Stage

    3 9 (38%) 8 (36%)
    4 12 (50%) 6 (27%)
    5 3 (13%) 8 (36%)
1 n (%); Median (IQR)

Group variables

Cleaning

Mobility plot

Bleeding plot

Periodontal pocket plot

Regression models

Mobility

Mobility 3D Replica Control
0 - Normal 84.7% 68.2%
1 - Abnormal 15.3% 31.8%
Total 100.0% 100.0%

Univariate analysis


    Pearson's Chi-squared test with Yates' continuity correction

data:  table(Mobility, Group)
X-squared = 4.4013, df = 1, p-value = 0.03591

Multivariate analysis

Characteristic OR1 95% CI1 p-value
Group

0.005
    3D Replica
    Control 3.83 1.47, 10.9
time

<0.001
    3 m
    6 m 0.13 0.04, 0.36
    12 m 0.06 0.01, 0.20
Sex

0.27
    Female
    Male 1.74 0.65, 4.69
1 OR = Odds Ratio, CI = Confidence Interval

“Bleeding on probing”

Bleeding 3D Replica Control
0 - Normal 97.2% 86.4%
1 - Abnormal 2.8% 13.6%
Total 100.0% 100.0%

Univariate analysis


    Pearson's Chi-squared test with Yates' continuity correction

data:  table(Bleeding, Group)
X-squared = 4.1536, df = 1, p-value = 0.04155

Multivariate analysis


Call:
glm(formula = as.factor(Bleeding) ~ Group + time + Sex, family = binomial, 
    data = clinical_long)

Coefficients:
             Estimate Std. Error z value Pr(>|z|)    
(Intercept)   -5.3124     1.1350  -4.680 2.86e-06 ***
GroupControl   2.2568     0.8454   2.670  0.00760 ** 
time6 m        0.3651     0.8598   0.425  0.67108    
time12 m       0.3651     0.8598   0.425  0.67108    
SexMale        2.1755     0.7470   2.912  0.00359 ** 
---
Signif. codes:  0 '***' 0.001 '**' 0.01 '*' 0.05 '.' 0.1 ' ' 1

(Dispersion parameter for binomial family taken to be 1)

    Null deviance: 76.745  on 137  degrees of freedom
Residual deviance: 60.781  on 133  degrees of freedom
AIC: 70.781

Number of Fisher Scoring iterations: 6

Pocket

Pocket 3D Replica Control
0 - Normal 97.2% 86.4%
1 - Abnormal 2.8% 13.6%
Total 100.0% 100.0%

Univariate analysis


    Pearson's Chi-squared test with Yates' continuity correction

data:  table(Pocket, Group)
X-squared = 4.1536, df = 1, p-value = 0.04155

Multivariate analysis


Call:
glm(formula = as.factor(Pocket) ~ Group + time + Sex, family = binomial, 
    data = clinical_long)

Coefficients:
             Estimate Std. Error z value Pr(>|z|)    
(Intercept)   -5.3124     1.1350  -4.680 2.86e-06 ***
GroupControl   2.2568     0.8454   2.670  0.00760 ** 
time6 m        0.3651     0.8598   0.425  0.67108    
time12 m       0.3651     0.8598   0.425  0.67108    
SexMale        2.1755     0.7470   2.912  0.00359 ** 
---
Signif. codes:  0 '***' 0.001 '**' 0.01 '*' 0.05 '.' 0.1 ' ' 1

(Dispersion parameter for binomial family taken to be 1)

    Null deviance: 76.745  on 137  degrees of freedom
Residual deviance: 60.781  on 133  degrees of freedom
AIC: 70.781

Number of Fisher Scoring iterations: 6

Modelling

Mobility model

Linear mixed model fit by REML. t-tests use Satterthwaite's method [
lmerModLmerTest]
Formula: 
Mobility ~ Group * time + `Age (surgery)` + Sex + `Total surgery time (min)` +  
    `Extra- alveolar time (s)` + `Moores Stage` + `Donor fitting times` +  
    (1 | id)
   Data: clinical_long

REML criterion at convergence: 132.9

Scaled residuals: 
     Min       1Q   Median       3Q      Max 
-1.64797 -0.74486 -0.00841  0.42711  2.27320 

Random effects:
 Groups   Name        Variance Std.Dev.
 id       (Intercept) 0.01223  0.1106  
 Residual             0.09386  0.3064  
Number of obs: 138, groups:  id, 46

Fixed effects:
                            Estimate Std. Error        df t value Pr(>|t|)    
(Intercept)                 0.449475   0.345442 35.529098   1.301 0.201580    
GroupControl                0.121499   0.106828 94.193338   1.137 0.258284    
time6 m                    -0.375000   0.088442 87.999998  -4.240 5.50e-05 ***
time12 m                   -0.416667   0.088442 87.999998  -4.711 9.14e-06 ***
`Age (surgery)`             0.001424   0.022670 34.000000   0.063 0.950298    
SexMale                     0.059302   0.071419 34.000000   0.830 0.412142    
`Total surgery time (min)`  0.004275   0.002148 34.000000   1.990 0.054665 .  
`Extra- alveolar time (s)` -0.001300   0.001105 34.000000  -1.177 0.247511    
`Moores Stage`4            -0.310120   0.081033 34.000000  -3.827 0.000530 ***
`Moores Stage`5            -0.389971   0.103990 34.000000  -3.750 0.000659 ***
`Donor fitting times`2     -0.008938   0.082902 34.000000  -0.108 0.914779    
`Donor fitting times`3     -0.052546   0.112550 34.000000  -0.467 0.643570    
`Donor fitting times`4      1.022147   0.293722 34.000000   3.480 0.001396 ** 
`Donor fitting times`5     -0.252938   0.305483 34.000000  -0.828 0.413448    
GroupControl:time6 m        0.011364   0.127888 87.999998   0.089 0.929398    
GroupControl:time12 m      -0.037879   0.127888 87.999998  -0.296 0.767784    
---
Signif. codes:  0 '***' 0.001 '**' 0.01 '*' 0.05 '.' 0.1 ' ' 1

Bleeding

Linear mixed model fit by REML. t-tests use Satterthwaite's method [
lmerModLmerTest]
Formula: 
Bleeding ~ Group * time + `Age (surgery)` + Sex + `Total surgery time (min)` +  
    `Extra- alveolar time (s)` + `Moores Stage` + `Donor fitting times` +  
    (1 | id)
   Data: clinical_long

REML criterion at convergence: -96.6

Scaled residuals: 
    Min      1Q  Median      3Q     Max 
-7.1625 -0.1608 -0.0532  0.0618  4.0847 

Random effects:
 Groups   Name        Variance Std.Dev.
 id       (Intercept) 0.03597  0.18965 
 Residual             0.00726  0.08521 
Number of obs: 138, groups:  id, 46

Fixed effects:
                             Estimate Std. Error         df t value Pr(>|t|)   
(Intercept)                -0.2297298  0.3211929 34.1332598  -0.715  0.47933   
GroupControl                0.0729192  0.0753630 39.5737721   0.968  0.33913   
time6 m                     0.0416667  0.0245969 88.0000023   1.694  0.09381 . 
time12 m                    0.0416667  0.0245969 88.0000023   1.694  0.09381 . 
`Age (surgery)`             0.0069052  0.0212915 33.9999907   0.324  0.74768   
SexMale                     0.1251724  0.0670775 33.9999938   1.866  0.07068 . 
`Total surgery time (min)`  0.0048846  0.0020176 33.9999939   2.421  0.02097 * 
`Extra- alveolar time (s)` -0.0001918  0.0010374 33.9999940  -0.185  0.85443   
`Moores Stage`4            -0.1765400  0.0761072 33.9999935  -2.320  0.02650 * 
`Moores Stage`5            -0.1841585  0.0976680 33.9999930  -1.886  0.06792 . 
`Donor fitting times`2     -0.1392278  0.0778619 33.9999939  -1.788  0.08267 . 
`Donor fitting times`3     -0.1129832  0.1057078 33.9999938  -1.069  0.29268   
`Donor fitting times`4      0.9337009  0.2758663 33.9999939   3.385  0.00181 **
`Donor fitting times`5     -0.3075329  0.2869123 33.9999941  -1.072  0.29133   
GroupControl:time6 m       -0.0416667  0.0355671 88.0000023  -1.171  0.24456   
GroupControl:time12 m      -0.0416667  0.0355671 88.0000023  -1.171  0.24456   
---
Signif. codes:  0 '***' 0.001 '**' 0.01 '*' 0.05 '.' 0.1 ' ' 1
We fitted a linear mixed model (estimated using REML and nloptwrap optimizer)
to predict Bleeding with Group, time, Age (surgery), Sex, Total surgery time
(min), Extra- alveolar time (s), Moores Stage and Donor fitting times (formula:
Bleeding ~ Group * time + `Age (surgery)` + Sex + `Total surgery time (min)` +
`Extra- alveolar time (s)` + `Moores Stage` + `Donor fitting times`). The model
included id as random effect (formula: ~1 | id). The model's total explanatory
power is substantial (conditional R2 = 0.91) and the part related to the fixed
effects alone (marginal R2) is of 0.48. The model's intercept, corresponding to
Group = 3D Replica, time = 3 m, Age (surgery) = 0, Sex = Female, Total surgery
time (min) = 0, Extra- alveolar time (s) = 0, Moores Stage = 3 and Donor
fitting times = 1, is at -0.23 (95% CI [-0.87, 0.41], t(120) = -0.72, p =
0.476). Within this model:

  - The effect of Group [Control] is statistically non-significant and positive
(beta = 0.07, 95% CI [-0.08, 0.22], t(120) = 0.97, p = 0.335; Std. beta = 0.27,
95% CI [-0.28, 0.82])
  - The effect of time [6 m] is statistically non-significant and positive (beta
= 0.04, 95% CI [-7.03e-03, 0.09], t(120) = 1.69, p = 0.093; Std. beta = 0.15,
95% CI [-0.03, 0.33])
  - The effect of time [12 m] is statistically non-significant and positive (beta
= 0.04, 95% CI [-7.03e-03, 0.09], t(120) = 1.69, p = 0.093; Std. beta = 0.15,
95% CI [-0.03, 0.33])
  - The effect of Age (surgery) is statistically non-significant and positive
(beta = 6.91e-03, 95% CI [-0.04, 0.05], t(120) = 0.32, p = 0.746; Std. beta =
0.05, 95% CI [-0.23, 0.33])
  - The effect of Sex [Male] is statistically non-significant and positive (beta
= 0.13, 95% CI [-7.64e-03, 0.26], t(120) = 1.87, p = 0.064; Std. beta = 0.46,
95% CI [-0.03, 0.95])
  - The effect of Total surgery time (min) is statistically significant and
positive (beta = 4.88e-03, 95% CI [8.90e-04, 8.88e-03], t(120) = 2.42, p =
0.017; Std. beta = 0.34, 95% CI [0.06, 0.61])
  - The effect of Extra- alveolar time (s) is statistically non-significant and
negative (beta = -1.92e-04, 95% CI [-2.25e-03, 1.86e-03], t(120) = -0.18, p =
0.854; Std. beta = -0.03, 95% CI [-0.38, 0.31])
  - The effect of Moores Stage [4] is statistically significant and negative
(beta = -0.18, 95% CI [-0.33, -0.03], t(120) = -2.32, p = 0.022; Std. beta =
-0.65, 95% CI [-1.20, -0.10])
  - The effect of Moores Stage [5] is statistically non-significant and negative
(beta = -0.18, 95% CI [-0.38, 9.22e-03], t(120) = -1.89, p = 0.062; Std. beta =
-0.68, 95% CI [-1.39, 0.03])
  - The effect of Donor fitting times [2] is statistically non-significant and
negative (beta = -0.14, 95% CI [-0.29, 0.01], t(120) = -1.79, p = 0.076; Std.
beta = -0.51, 95% CI [-1.08, 0.05])
  - The effect of Donor fitting times [3] is statistically non-significant and
negative (beta = -0.11, 95% CI [-0.32, 0.10], t(120) = -1.07, p = 0.287; Std.
beta = -0.42, 95% CI [-1.19, 0.35])
  - The effect of Donor fitting times [4] is statistically significant and
positive (beta = 0.93, 95% CI [0.39, 1.48], t(120) = 3.38, p < .001; Std. beta
= 3.43, 95% CI [1.43, 5.44])
  - The effect of Donor fitting times [5] is statistically non-significant and
negative (beta = -0.31, 95% CI [-0.88, 0.26], t(120) = -1.07, p = 0.286; Std.
beta = -1.13, 95% CI [-3.22, 0.96])
  - The effect of Group [Control] × time [6 m] is statistically non-significant
and negative (beta = -0.04, 95% CI [-0.11, 0.03], t(120) = -1.17, p = 0.244;
Std. beta = -0.15, 95% CI [-0.41, 0.11])
  - The effect of Group [Control] × time [12 m] is statistically non-significant
and negative (beta = -0.04, 95% CI [-0.11, 0.03], t(120) = -1.17, p = 0.244;
Std. beta = -0.15, 95% CI [-0.41, 0.11])

Standardized parameters were obtained by fitting the model on a standardized
version of the dataset. 95% Confidence Intervals (CIs) and p-values were
computed using a Wald t-distribution approximation.

Pocket

Linear mixed model fit by REML. t-tests use Satterthwaite's method [
lmerModLmerTest]
Formula: 
Pocket ~ Group * time + `Age (surgery)` + Sex + `Total surgery time (min)` +  
    `Extra- alveolar time (s)` + `Moores Stage` + `Donor fitting times` +  
    (1 | id)
   Data: clinical_long

REML criterion at convergence: -96.6

Scaled residuals: 
    Min      1Q  Median      3Q     Max 
-7.1625 -0.1608 -0.0532  0.0618  4.0847 

Random effects:
 Groups   Name        Variance Std.Dev.
 id       (Intercept) 0.03597  0.18965 
 Residual             0.00726  0.08521 
Number of obs: 138, groups:  id, 46

Fixed effects:
                             Estimate Std. Error         df t value Pr(>|t|)   
(Intercept)                -0.2297298  0.3211929 34.1332598  -0.715  0.47933   
GroupControl                0.0729192  0.0753630 39.5737721   0.968  0.33913   
time6 m                     0.0416667  0.0245969 88.0000023   1.694  0.09381 . 
time12 m                    0.0416667  0.0245969 88.0000023   1.694  0.09381 . 
`Age (surgery)`             0.0069052  0.0212915 33.9999907   0.324  0.74768   
SexMale                     0.1251724  0.0670775 33.9999938   1.866  0.07068 . 
`Total surgery time (min)`  0.0048846  0.0020176 33.9999939   2.421  0.02097 * 
`Extra- alveolar time (s)` -0.0001918  0.0010374 33.9999940  -0.185  0.85443   
`Moores Stage`4            -0.1765400  0.0761072 33.9999935  -2.320  0.02650 * 
`Moores Stage`5            -0.1841585  0.0976680 33.9999930  -1.886  0.06792 . 
`Donor fitting times`2     -0.1392278  0.0778619 33.9999939  -1.788  0.08267 . 
`Donor fitting times`3     -0.1129832  0.1057078 33.9999938  -1.069  0.29268   
`Donor fitting times`4      0.9337009  0.2758663 33.9999939   3.385  0.00181 **
`Donor fitting times`5     -0.3075329  0.2869123 33.9999941  -1.072  0.29133   
GroupControl:time6 m       -0.0416667  0.0355671 88.0000023  -1.171  0.24456   
GroupControl:time12 m      -0.0416667  0.0355671 88.0000023  -1.171  0.24456   
---
Signif. codes:  0 '***' 0.001 '**' 0.01 '*' 0.05 '.' 0.1 ' ' 1

All regression plots

All Regression tables

Characteristic Mobility Bleeding on probing Pocket
Beta 95% CI1 p-value Beta 95% CI1 p-value Beta 95% CI1 p-value
Group








    3D Replica


    Control 0.12 -0.09, 0.33 0.3 0.07 -0.08, 0.23 0.3 0.07 -0.08, 0.23 0.3
time








    3 m


    6 m -0.38 -0.55, -0.20 <0.001 0.04 -0.01, 0.09 0.094 0.04 -0.01, 0.09 0.094
    12 m -0.42 -0.59, -0.24 <0.001 0.04 -0.01, 0.09 0.094 0.04 -0.01, 0.09 0.094
Age (surgery) 0.00 -0.04, 0.05 >0.9 0.01 -0.04, 0.05 0.7 0.01 -0.04, 0.05 0.7
Sex








    Female


    Male 0.06 -0.09, 0.20 0.4 0.13 -0.01, 0.26 0.071 0.13 -0.01, 0.26 0.071
Total surgery time (min) 0.00 0.00, 0.01 0.055 0.00 0.00, 0.01 0.021 0.00 0.00, 0.01 0.021
Extra- alveolar time (s) 0.00 0.00, 0.00 0.2 0.00 0.00, 0.00 0.9 0.00 0.00, 0.00 0.9
Moores Stage








    3


    4 -0.31 -0.47, -0.15 <0.001 -0.18 -0.33, -0.02 0.027 -0.18 -0.33, -0.02 0.027
    5 -0.39 -0.60, -0.18 <0.001 -0.18 -0.38, 0.01 0.068 -0.18 -0.38, 0.01 0.068
Donor fitting times








    1


    2 -0.01 -0.18, 0.16 >0.9 -0.14 -0.30, 0.02 0.083 -0.14 -0.30, 0.02 0.083
    3 -0.05 -0.28, 0.18 0.6 -0.11 -0.33, 0.10 0.3 -0.11 -0.33, 0.10 0.3
    4 1.0 0.43, 1.6 0.001 0.93 0.37, 1.5 0.002 0.93 0.37, 1.5 0.002
    5 -0.25 -0.87, 0.37 0.4 -0.31 -0.89, 0.28 0.3 -0.31 -0.89, 0.28 0.3
Group * time








    Control * 6 m 0.01 -0.24, 0.27 >0.9 -0.04 -0.11, 0.03 0.2 -0.04 -0.11, 0.03 0.2
    Control * 12 m -0.04 -0.29, 0.22 0.8 -0.04 -0.11, 0.03 0.2 -0.04 -0.11, 0.03 0.2
1 CI = Confidence Interval

Tidymodels

            Truth
Prediction   3D Replica Control
  3D Replica         11       7
  Control             4      13
# A tibble: 2 × 3
  .metric  .estimator .estimate
  <chr>    <chr>          <dbl>
1 accuracy binary         0.686
2 kap      binary         0.374