Artificial neural network, genetic algorithm, and logistic regression applications for predicting renal colic in emergency settings
 Cenker Eken^{1}Email author,
 Ugur Bilge^{2},
 Mutlu Kartal^{1} and
 Oktay Eray^{1}
DOI: 10.1007/s1224500901031
© SpringerVerlag London Ltd 2009
Received: 3 March 2009
Accepted: 13 April 2009
Published: 3 June 2009
Abstract
Background
Logistic regression is the most common statistical model for processing multivariate data in the medical literature. Artificial intelligence models like an artificial neural network (ANN) and genetic algorithm (GA) may also be useful to interpret medical data.
Aims
The purpose of this study was to perform artificial intelligence models on a medical data sheet and compare to logistic regression.
Methods
ANN, GA, and logistic regression analysis were carried out on a data sheet of a previously published article regarding patients presenting to an emergency department with flank pain suspicious for renal colic.
Results
The study population was composed of 227 patients: 176 patients had a diagnosis of urinary stone, while 51 ultimately had no calculus. The GA found two decision rules in predicting urinary stones. Rule 1 consisted of being male, pain not spreading to back, and no fever. In rule 2, pelvicaliceal dilatation on bedside ultrasonography replaced no fever. ANN, GA rule 1, GA rule 2, and logistic regression had a sensitivity of 94.9, 67.6, 56.8, and 95.5%, a specificity of 78.4, 76.47, 86.3, and 47.1%, a positive likelihood ratio of 4.4, 2.9, 4.1, and 1.8, and a negative likelihood ratio of 0.06, 0.42, 0.5, and 0.09, respectively. The area under the curve was found to be 0.867, 0.720, 0.715, and 0.713 for all applications, respectively.
Conclusion
Data mining techniques such as ANN and GA can be used for predicting renal colic in emergency settings and to constitute clinical decision rules. They may be an alternative to conventional multivariate analysis applications used in biostatistics.
Keywords
Artificial neural network Genetic algorithm Logistic regression Renal colic Emergency departmentIntroduction
There are many articles in the medical literature measuring diagnostic tools for patients with acute flank pain. The main purpose of these studies is to find the safest and most costeffective way to detect urinary stones in the emergency department (ED). Logistic regression is mostly used in these studies in processing multivariate data. Alternative methods in data mining, also known as artificial intelligence, should also be used to evaluate the medical data sheet.
An artificial neural network (ANN) is an information processing tool that is inspired by the structure and function of the human brain. The human central nervous system is composed of a series of interconnecting neurons separated by synapses, and scientists have demonstrated information transfer via a series of action potentials [1]. The brain learns by adjusting the number and strength of these connections. McCulloch and Pitts [2] first described ANNs as a method of information processing using a network of binary decision elements or “neurons.” Later efforts were made in order to explain complex processes of the central nervous system [3]. A neural network is composed of a series of interconnecting parallel nonlinear processing elements (nodes) resembling biological neurons.
A genetic algorithm (GA) [4, 5] is a good method for finding quick solutions to hard combinatorial optimization problems where there are too many combinations to search and were first put forward by John Holland as a search and optimization technique. A GA typically generates a random population of possible rule hypotheses and tests them with a given fitness function. In a standard GA, solution hypotheses are represented as code strings; this is also called a genotype where genetic operators such as crossover and mutation are applied. The resulting phenotypes are then assessed by applying the fitness function to each one of them. At each iteration the GA applies the principles of natural evolution to the population of hypotheses, that is, selecting the fittest hypotheses using the fitness function as well as applying mutation and crossover to the population.
In our first article [6], we tested a current algorithm and investigated the clinical characteristics of renal colic patients in the ED. The objective of this study was to compare predictive values of multiple statistical models for diagnosing renal colic patients in the same data set.
Material and methods
Data collection
Parameter  Type 

Gender  Coded (2 codes, i.e., male, female) 
Number of attacks  Coded (2 codes, i.e., first, more than one) 
Coded as discrete variable for GA  
Triggered by exercise  Coded (2 codes; 1 for yes and 0) 
Previous presentation  Coded (2 codes; 1 for yes and 0) 
History of urolithiasis  Coded (2 codes; 1 for yes and 0) 
Family history of urolithiasis  Coded (2 codes; 1 for yes and 0) 
Comorbid disease  Coded (2 codes; 1 for yes and 0) 
Nausea  Coded (2 codes; 1 for yes and 0) 
Vomiting  Coded (2 codes; 1 for yes and 0) 
Sweating  Coded (2 codes; 1 for yes and 0) 
Fever  Coded (2 codes; 1 for yes and 0) 
Dysuria  Coded (2 codes; 1 for yes and 0) 
Hematuria  Coded (2 codes; 1 for yes and 0) 
Unable to void  Coded (2 codes; 1 for yes and 0) 
Tenderness in costovertebral region  Coded (2 codes; 1 for yes and 0) 
Tenderness on ureteral tract  Coded (2 codes; 1 for yes and 0) 
Suprapubic tenderness  Coded (2 codes; 1 for yes and 0) 
Abdominal rigidity  Coded (2 codes; 1 for yes and 0) 
Rebound  Coded (2 codes; 1 for yes and 0) 
Positional discomfort  Coded (2 codes; 1 for yes and 0) 
Positive urine analysis (≥10 red blood cells)  Coded (2 codes; 1 for yes and 0) 
Pelvicaliceal dilatation on bedside ultrasonography  Coded (2 codes; 1 for yes and 0) 
Colic pain  Coded (2 codes; 1 for yes and 0) 
Radiation to the groin  Coded (2 codes; 1 for yes and 0) 
0 = no radiation  
1 = radiation to the belly  
2 = radiation to the groin  
3 = radiation to the back for GA codes 
Statistical analyses
Artificial neural network
A feedforward ANN with backpropagation was performed by JMP (release 6.0, a business unit of SAS). In large data sets, a data set is divided as a training set and a test set to avoid overfitting which is a problem when ANN learns the training set too accurately yet it cannot generalize when presented with a new test set. However, for the small data sets, the kfold crossvalidation model is suggested to avoid overfitting. The kfold crossvalidation method separates the data into k sets and assigns one of the k sets as the test set and the remaining as the training set. We performed 10fold crossvalidation with 2 hidden units, 500 iterations, and 20 tours. The overfit penalty was assigned as 0.001 and convergence criterion was chosen as 0.00001.
Genetic algorithm
The GA program SimMine is part of a data mining software package developed by SimWorld Limited, UK (www.simworld.co.uk). The system allows the selection of flat or hierarchical chromosome types and allows preprocessing the data by scaling, taking first differences and dividing continuous data into categories. As GA normally operate on categorical data, when the input parameters are a mixture of numerical and coded values, the system converts numerical values into a number of categories. The system allows users to select the total number of chromosomes (the population size) and the number of top scoring individuals that survive to the next generation.
Fitness score
As can be seen above, the GA could achieve a maximum score of 1 when it identifies all positives correctly, and would have a false_positive of 0.
We used the software previously on data mining tasks at Akdeniz University Hospital with good results [3].
Logistic regression
The Statistical Package for the Social Sciences (SPSS 13.0 for Windows) was used for binary logistic regression analysis. Like in GA and ANN, 24 independent variables were assigned to predict the renal colic as the dependent variable. A stepwise forward logistic regression analysis was performed. We tested the fitness of the logistic regression model with the HosmerLemeshow goodnessoffit statistic.
To compare the overall performances of all applications, sensitivity, specificity, positive predictive value, and negative predictive value of all applications were determined. And also a receiveroperating characteristic curve (ROC) analysis was performed; p ≥ 0.05 was accepted as significant.
Results
Demographics and univariate data analysis of patients with renal colic
Variable  Patients with urinary stone  %  p 

Age  38.4 ± 14  
Gender: male/female  128/48  87/60  0.000 
More than one attack  98  81  0.182 
Colic pain  24  75  0.711 
Radiation to the groin  120  81.6  0.045 
Positional discomfort  23  79.3  0.806 
Previous presentation  69  89.6  0.002 
History of urolithiasis  104  86  0.001 
Family history of urolithiasis  85  81.7  0.163 
Comorbid disease  33  73.3  0.451 
Nausea  126  83.4  0.003 
Vomiting  73  85.9  0.020 
Sweating  74  84  0.060 
Fever  9  60  0.092 
Dysuria  80  80  0.429 
Hematuria  57  86.4  0.041 
Unable to void  26  84  0.363 
Tenderness in costovertebral region  150  80.2  0.036 
Tenderness on ureteral tract  101  79  0.573 
Suprapubic tenderness  40  70.2  0.124 
Abdominal rigidity  9  90  0.334 
Rebound  3  100  0.348 
Positional discomfort  36  80  0.658 
Positive urine analysis  121  83  0.010 
Pelvicaliceal dilatation on bedside US  142  81.6  0.008 
Artificial neural network
Genetic algorithm results
We used the GA population size of 128, and the top scoring 32 individuals were selected as fit to survive in the next generation of solutions; the search was stopped after no improvement was seen for the last 25 iterations of each run. The default value for the crossover rate was 60%, and the mutation rate was 20% per chromosome.
When we apply the GA, the system quickly converges into simple rules. Modifying the crossover rate or the mutation rate does not improve the results.
The best rule to explain urinary stone = 1 is presented below:
Rule 1:

Total samples = 227

Positive_count = 176 (total of 176 cases of urinary stone is 1)

True_positive = 119 (the rule above explains 119 of the 176)

Negative_count = 51 (total of 51 cases where urinary stone is 0)

False_positive = 12 (the rule is wrong in 12 of 51 cases)

Fitness score = 0.4408

Sensitivity = 67.61%

Specificity = 76.47%

Positive predictive value = 90.84%

Negative predictive value = 40.6%

Positive likelihood ratio: 2.9

Negative likelihood ratio: 0.42

Area under the curve = 72.04%
This rule can be explained in a more articulate form as “the patient has urinary stone if: the gender is male, and the pain radiates to groin and belly or no pain radiation (codes: 0, 1, or 2), and has no fever”. As there are 4 types of pain (they are 0, 1, 2, and 3 as can be seen in the “Data collection” section), we can reword the rule as “the patient has urinary stone if: the gender is male, and the pain does not radiate to the back, and the patient has no fever.”
A second rule that was also found, which has slightly less fitness value but worth reporting, is shown below:
Rule 2:

Total samples = 227

Positive_count = 176 (total of 176 cases of urinary stone is 1)

True_positive = 100 (the rule above explains 100 of the 176)

Negative_count = 51 (total of 51 cases where urinary stone is 0)

False_positive = 7 (the rule is wrong in 7 of 51 cases)

Fitness score = 0.4309

Sensitivity = 56.82%

Specificity = 86.27%

Positive predictive value = 93.46%

Negative predictive value = 36.7%

Positive likelihood ratio: 4.1

Negative likelihood ratio: 0.5

Area under the curve = 71.55%
This rule can be also explained in a more articulate form as “the patient has urinary stone if: the gender is male, and the pain does not radiate to the back, and has pelvicaliceal dilation on bedside ultrasonography (US).”
Logistic regression
With the forward stepwise conditional method, the logistic regression model with 24 independent variables mentioned above revealed 168 of 176 patients with renal colic and 24 of 51 patients without renal colic. So it had a sensitivity of 95.5% and specificity of 47.1%. The positive predictive value was 86.2% and negative predictive value was 75.3%. The positive predictive value of logistic regression was 1.8 and negative predictive value was 0.09. The AUC for the logistic regression model was 0.841 (p = 0.000).
Gender (to be male) [odds ratio (OR): 5.567, 95% confidence interval (CI): 2.34–13.24, p = 0.000], history of urolithiasis (OR: 2.72, 95% CI: 1–7.3, p = 0.047), and nausea (OR: 3, 95% CI: 1.12–8.5, p = 0.029) were found to be independent factors in predicting urinary stones in logistic regression analysis.
Overall performances of each application
Application  Sensitivity  Specificity  PLR  NLR  AUC 

ANN  94.9  78.4  4.4  0.06  0.867 
GA rule 1  67.6  76.47  2.9  0.42  0.720 
GA rule 2  56.8  86.3  4.1  0.5  0.715 
Logistic regression  95.5  47.1  1.8  0.09  0.713 
Discussion
We are in the process of applying the technology to other data mining tasks in the hospital databases. We are aiming for an automated approach to explore and reveal hidden, unknown relationships in data. We wanted to enrich the ANN and GA data mining techniques with a logistic regression processing module and also to compare the fitness functions using statistical techniques.
In medical research, efforts are expended to detect a disease most accurately or predict the prognosis of a specific group of patients. Logistic regression analysis is the most frequently used statistical analysis for evaluating multiple independent variables through a dependent outcome in medical research. Although ANN and GA have been used commonly in other industries, they do not have widespread use in medicine so far. Here we show that both ANN and GA can be used for constituting prediction models and decision rules as well as logistic regression analysis.
ANN emerged as the best technique in predicting renal colic according to the results of this study. For ANN both the sensitivity (94.9%) and PLR (4.4) were higher than for the other models. The AUC was also found to be higher than with logistic regression and GA. However, overfitting is a major problem in ANN applications. In order to prevent overfitting, the data set must be separated randomly as the training set and test set. After the learning process of ANN by using the training set, the model should be tested in unseen data, a test set and sometimes a validation set. However, this is not always possible for small data sets. The kfold crossvalidation that we performed in this study separates the data sets into k groups and uses the groups as the data test set and the remaining as the training set. Although kfold crossvalidation was used, to test ANN in an unseen data test would be better. Even so the results are promising for ANN. ANN previously has been used for predicting genetic factors in stone disease [7], stone composition [8], spontaneous passage of ureteral calculi [9], and outcome after extracorporeal shock wave lithotripsy (ESWL) [10]. So far there is only one study detecting the performance of ANN in predicting the presence of renal calculi [11]. Tanthanuch and Tanthanuch studied 168 patients with renal calculi, 100 patients for the training set and 68 patients for the test set. After assuming a probability of 65% or more as having renal calculi, they found that ANN was 100% accurate in predicting renal calculi for the testing data. However, the study population they investigated consisted of only patients with renal calculi. Thus, ANN was trained and tested only in patients with renal calculi. The performance of ANN was not tested in patients without a renal calculus. This is a limitation of their study.
GAs are relatively new search techniques which have been used in optimization, scheduling, and planning tasks, and there is a huge amount of background literature on them. As in other industries, they are increasingly being used in medical data mining tasks. Our application of GA found useful relationships for predicting renal colic. Especially the PLR of the second rule was worth mentioning. The advantage of GA is to discover simple predictive rules. In the first rule of GA, to be male, having pain not radiating to the back, and having no fever composed the independent variables. In the second rule, pelvicaliceal dilatation on bedside US replaced having no fever. The PLR (4.1) of the second rule seems better than the first rule. And the specificity of the second rule (86.3%) was better than the first rule (76.5%). However, the sensitivity of the first rule (67.6%) was better than the second rule (56.8%).
Logistic regression emerges as the best model in this study in excluding renal colic. The NLR of logistic regression was 0.09, and also the NLR of ANN was 0.06, which is also reasonable to mention. But the overfitting problem has to be taken into consideration for ANN as mentioned above. Furthermore, gender (to be male), nausea, and history of urolithiasis were found to be the independent variables in predicting urinary stones.
One can also constitute simple prediction rules both by ANN and logistic regression applications. After analyzing the significant variables in the univariate analysis or by using the likelihood ratios, it is possible to compose a prediction model by assigning significant variables into the ANN and logistic regression analysis. Furthermore, the independent variables that are statistically significant in a multivariate regression analysis can also be used to compose a prediction model. We preferred to use all of the variables (24 variables) for all the models in order to prevent bias. Different models for renal colic need to be tested in further studies.
Conclusion and future work
Data mining techniques, particularly ANN rather than GA, have been used in order to solve problems in the ED like diagnosing pathological conditions such as cardiac ischemia, craniocervical junction injury in trauma patients, and pneumonia, predicting the prognosis of patients in the ED, and also possible ED visits of patients because of respiratory symptoms [12–16]. This study also showed that data mining techniques such as ANN and GA could be used for predicting or excluding renal colic in emergency settings and to constitute clinical decision rules. Data mining techniques should be useful tools to solve the sophisticated issues in the ED in the future. They may also be an alternative to conventional multivariate analysis applications used in biostatistics. Further studies are needed to validate these data mining techniques in predicting either renal colic or complicated points in the ED.
Notes
Declarations
Acknowledgement
This study was supported by Akdeniz University Investigation Foundation. We are also grateful to the residents and physicians in the emergency department.
Authors’ Affiliations
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