Of the 326 patients enrolled in this study, 152 (46.6%) had acute appendicitis, while 174 (53.4%) were discharged. Significant differences were observed in terms of age (p < 0.01), complaints (p < 0.001), urine glucose (p < 0.001), and urine ketone (p < 0.001), among the acute appendicitis patients (mean age, 36.57 years) and the discharged patients (mean age, 43.05 years). Abdominal and RLQ pains were the most common complaints presented in the emergency medical center (Table ).
In terms of blood test findings, white blood cell (p < 0.001), red blood cell (p < 0.01), neutrophils (p < 0.001), glucose (p < 0.01), total bilirubin (p < 0.001), direct bilirubin (p < 0.001), and activated partial thromboplastin time (p < 0.01) were significantly or slightly higher in patients with acute appendicitis, whereas lymphocytes (p < 0.001), monocytes (p < 0.001), eosinophils (p < 0.001), basophils (p < 0.001), large unstained cells (p < 0.001), sodium (p < 0.001), chloride (p < 0.001), lipase (p < 0.001), and total amylase (p < 0.001) were significantly higher in discharged patients. The remaining variables could not be used to differentiate acute appendicitis from the discharged patients (Table ).
| Table 2Comparison of patient characteristics (CBC & Differential Count, Serum Electrolytes, Routine Admission, etc.) for acute appendicitis and discharged patients (n = 326) |
In the multivariate analysis, independent risk factors were identified using Wald forward logistic regression, to define entry and removal criteria of 0.01 and 0.05, or 0.05 and 0.10, respectively. Regardless of the criteria used, the independent risk factors provided the same results using the two logistic models. We included six variables in the final logistic regression that were independently associated with acute appendicitis: complaints, urine glucose, white blood cell, neutrophils, total bilirubin, and lipase (Table ). These variables were tested by linear regression analysis to evaluate multicollinearity among the predictors. The data did not violate the multicollinearity assumption. The tolerance of each independent variable was greater than 0.616. The variance inflation factor (VIF) values of the variables ranged from 1.005 to 1.624. The ACC, SENS, SPEC, PPV, and NPV, were 79.8%, 76.3%, 82.8%, 79.5%, and 80.0%, respectively. The AUC of the models was 79.5% (95% CI, 74.7-83.8), indicating fair discriminatory power. The goodness-of-fit (H) statistic indicated that the models were well calibrated (p = 0.838).
| Table 3Multivariate analysis of predictors of acute appendicitis (entry and removal criteria of 0.01 and 0.05, or 0.05 and 0.10) |
Decision support model based on multivariate analysis
Five of the six variables (Table ) were selected by the C5.0 decision tree model and their importance was defined in the following order: neutrophils, complaints, total bilirubin, urine glucose, and lipase. The cut-off points were determined using the C5.0 decision tree algorithm and the criteria for dichotomizing the continuous variables were all statistically significant (p < 0.05) except for LUQ pain (OR, 0.732; 95% CI, 0.014-37.307; p = 0.876). The results are summarized in Table . The decision support model is shown in Figure and eight decision rules were generated from the full dataset. Seven decision rules (in Figure , leaf nodes 1, 5, 7, 8, 10, 11, and 12) were statistically significant, excluding leaf node LUQ (node 9). Three rules were associated with acute appendicitis as follows: 1) neutrophils > 73.1% and urine glucose is positive (p < 0.01); 2) neutrophils > 73.1% and urine glucose is negative and periumbilical area pain, or upper abdominal pain, or RLQ pain (p < 0.001); 3) neutrophils > 73.1% and urine glucose is negative and abdominal pain, and total bilirubin > 1.0 mg/dL, and lipase ≤ 46 U/L (p < 0.05). The ACC, SENS, SPEC, PPV, NPV, and AUC measures were 82.5%, 74.3%, 89.7%, 86.3%, 80.0%, and 82.0% (95% CI, 77.4-86.0), respectively.
| Table 4Statistical significance of cut-off points determined using the C5.0 decision tree algorithm (for multivariate analysis) |
Decision support model based on univariate analysis
Sixteen of the 20 variables with p < 0.01 (Tables and ) were selected by the C5.0 decision tree algorithm and their importance was defined in the following order: lymphocytes, urine glucose, total bilirubin, total amylase, chloride, red blood cell, neutrophils, eosinophils, white blood cell, complaints, basophils, glucose, monocytes, activated partial thromboplastin time, urine ketone, and direct bilirubin. The criteria for the selected cut-off points are summarized in Table . The decision support model for the diagnosis of acute appendicitis is shown in Figure and its performance was 93.9%, 89.5%, 97.7%, 97.1%, 91.4%, and 93.6% (95% CI, 90.4-96.0). We generated 29 decision rules, i.e., 16 for acute appendicitis and 13 for the control group. Thirteen decision rules (in Figure : leaf nodes 6, 11, 15, 20, 22, 28, 39, 40, 41, 44, 45, 47, and 49) were statistically significant. Seven rules were associated with acute appendicitis as follows: 1) lymphocytes ≤ 20.2% and urine glucose is positive (p < 0.01); 2) lymphocytes ≤ 20.2% and urine glucose is negative and lower abdominal pain and direct bilirubin > 0.4 mg/dL (p < 0.05); 3) lymphocytes ≤ 20.2% and urine glucose is negative and RLQ pain and chloride > 104 mmol/L and urine ketone is negative and monocytes > 3.6% (p < 0.05); 4) lymphocytes ≤ 20.2% and urine glucose is negative and RLQ pain and chloride > 104 mmol/L and urine ketone is negative and monocytes ≤ 3.6% and eosinophils > 1.5% (p < 0.05); 5) lymphocytes ≤ 20.2% and urine glucose is negative and abdominal pain and total bilirubin ≤ 1.0 mg/dL and total amylase ≤ 58 U and monocytes ≤ 2.4% (p < 0.05); 6) lymphocytes ≤ 20.2% and urine glucose is negative and abdominal pain and total bilirubin > 1.0 mg/dL and activated partial thromboplastin time > 22.6 s and neutrophils ≤ 84% and lymphocytes > 13.8% (p < 0.05); 7) lymphocytes ≤ 20.2% and urine glucose is negative and abdominal pain and total bilirubin ≤ 1.0 mg/dL and total amylase ≤ 58 U and monocytes > 2.4% and eosinophils ≤ 2.4% and urine ketone is negative and glucose ≤ 124 mg/dL and chloride ≤ 107 mmol/L (p < 0.05).
| Table 5Statistical significance of cut-off points determined using the C5.0 decision tree algorithm (for univariate analysis) |
The six measures were compared using a 10-fold cross validation to assess the generalization ability of these decision support models. The differences in the clinical factors selected before and after the application of the C5.0 decision tree algorithm are shown in Tables and . This showed that the decision support model based on univariate analysis was superior to those based on multivariate analyses with different conditions (Table ). The decision support model based on the univariate analysis was statistically superior to those based on multivariate analyses in terms of predictive power and discriminatory capacity, which was expressed by the area under the ROC curve (p < 0.01, 95% CI, 3.13-14.5; p < 0.05, 95% CI, 1.54-13.1; Table and Figure ). The decision support model based on multivariate analysis using loose criteria was also better than that using strict criteria, especially the AUC measure, although the discriminatory power between the two models was not statistically significant (p = 0.400; 95% CI, -2.0-5.02).
| Table 6Clinical factors selected before the application of C5.0 decision tree algorithm during 10-fold cross validation |
| Table 7Clinical factors selected after the application of C5.0 decision tree algorithm during 10-fold cross validation |
| Table 8Performance of decision support models based on univariate and multivariate analysis (10-fold cross validation) |
| Table 9Discriminatory capacity of decision support models used for the diagnosis of acute appendicitis expressed as areas under ROC curves (95% CI) |