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Original Clinical Research
Journal of Chinese Integrative Medicine: Volume 6, 2008   Issue 11
Statistical validation of strategies for Zang-Fu single patterndifferentiation
Arthur de Sá FERRE (Physical Therapy Research Group, Department of Physical Therapy, Centro Universitrio Augusto Motta, Rio de Janeiro, Brazil E-mail: arthur_sf@ig.com.br)

Objective: To propose and validate a method to aid traditional Chinese medicine (TCM) physicians in differentiation of Zang-Fu single patterns.

Methods: The procedure started with data collection and search on a knowledge database. Candidate patterns were selected and ranked according to the relative amount of explained exam's manifestations. Diagnosis identification was performed on a list of diagnostic hypotheses. Validation was conducted with 96 600 simulations of manifestation profiles obtained from database. Statistical performance based on confusion matrices was assessed for individual methods including inspection, auscultation and olfaction, inquiry, and palpation. Combined methods (inspection+auscultation and olfaction, inspection+auscultation and olfaction+inquiry) and four methods (inspection+auscultation and olfaction+inquiry+palpation) were also tested.

Results: The highest accuracy was obtained with the inquiry method (89.7%), followed by inspection (70.7%), auscultation and olfaction (59.9%), and palpation (56.1%). The same sequence was found for both sensitivity and negative predictive values. Specificity and positive predictive values were almost equal and high (>99%) among individual exam methods. The combination of all methods provided the highest accuracy (93.2%), sensitivity (86.5%), and negative predictive value (88.1%), while sustained high specificity (99.9%) and positive predictive value (99.8%). The four methods presented the higher performance compared to combination of two or three exam methods as well as all single exam methods.

Conclusion: The proposed strategies present statistical evidence of its diagnostic performance and can be used to aid TCM physicians in making single pattern diagnosis according to Zang-Fu theory.

Ferreira AS. J Chin Integr Med/Zhong Xi Yi Jie He Xue Bao. 2008; 6(11): 1109-1116. Received July 30, 2008; published online November 15, 2008. Free full text (PDF) is available at www.jcimjournal.com. Indexed/abstracted in and full text link-out at PubMed. Forward linking and reference linking via CrossRef. DOI: 10.3736/jcim20081103

 

Correspondence: Arthur de Sá FERREIRA, PhD, Professor; Fax: 55(21)-3977-8950; E-mail: arthur_sf@ig.com.br

  

1   Introduction
      Diagnosis in traditional Chinese medicine (TCM) is achieved using four methods (FMs)
1-3: inspection, auscultation and olfaction, inquiry, and palpation (Figure 1). These classical methods derive from the perspective that ancient Chinese physicians attempted to establish one's health status based on his or her external appearance and behavior, instead of developing diagnostic instruments for disease identification. Classic literatures4-8 state that "superior" TCM doctors collected data from patients according to the FMs and interpreted those manifestations using medical theories, obtaining a high cure rate of 90%; "mediocre" and "inferior" doctors had cure rates of 70%-80% and 60% patients, respectively. FM diagnosis is based on qualitative information obtained by the five senses and seem not to be suitable at the present time2. Thus, researchers begun to apply computer-based techniques for knowledge discovery2, physiological understanding9, tongue observation10-12, pulse palpation13, and also diagnosis1, 3, 14-17.
    

Figure 1   Scheme for traditional Chinese medicine diagnosis separated by exam method
    
   Occidental medical diagnosis uses deductive-inductive reasoning, applying tests that confirm a target hypothesis, eliminate an alternative hypothesis, or discriminate among competing ones
18. Similar strategies were not found on the consulted classic TCM books4-8 and are still emerging on present literatures 16, 17, 19. Wang et al 1 stated that TCM diagnosis could be understood as a pattern recognition problem, where manifestation profile defined a diagnosis. Patterns or syndromes are manifestation profiles (signs and symptoms) already arranged and classified according to TCM theories. It is based on pattern differentiation—together with the subject's health status and climate—that a physician designs and implements treatment. Hence, pattern differentiation is a necessary process for successful TCM treatment.
   If it was possible, TCM physicians should rely only on pathognomonic manifestations to perform diagnosis
20. However, not all patterns exhibit such feature, and many of those share common manifestations. Moreover, patterns have several manifestations which can be present or do not depend on individual constitution and environmental factors. Because of the above-mentioned issues, the use of computer-based analysis becomes very useful in TCM.
   The aim of this work is to propose and validate a method to aid TCM physicians in differentiation of Zang-Fu patterns. It was hypothesized that manifestations describing patterns provide sufficient qualitative information to allow Zang-Fu single pattern differentiation when all FMs are used to assess the subject health status. The rationales of the method are discussed and its validity is assessed with simulations of manifes-tation profiles.

 
  

2   Materials and methods
2.1   Method for Zang-Fu single pattern differentiation   The method for Zang-Fu single pattern differentiation was performed in a three-stage schema (Figure 2): 1) data collection and knowledge database search; 2) selection of candidate patterns and hypothesis classification; and 3) diagnosis identification. It was assumed that all manifestations collected from the patients were dichotomous (present/absent) and must be explained regardless of its clinical appearance (mild or severe, acute or chronic, etc.).

    

Figure 2   Flowchart of the proposed method for Zang-Fu single pattern differentiation
    
   The first stage comprised data collection and database search. During data entry from the patient's exam, the diagnostic algorithm searched for free terms and quoted phrases, e.g., headache and "headache". The former recalls patterns with headache within its manifestation profile (ocular headache, occipital headache, etc.); the latter recalls patterns with the exact term. Combinatorial procedure
21 was used after data collection because the diagnosis did not depend on the sequence of the results obtained during the exam22.
   At the second stage, a pattern was considered as a "candidate" if it presented at least one manifes-tation collected at the exam. The "strength" of indication of the candidate pattern for diagnosis was calculated using the following equation.
   F%=NE/NP×100%
NE is the count of explained manifestations of a pattern in the database, and NP is the count of collected manifestations during patient exam. This step is important since it recalls any possibility (F%
0) within the database and increases sensitivity of the algorithm. The candidates selected at this stage are ranked in descent order of F% and represent a list of diagnostic hypotheses (DHs).
   The last stage identified the diagnosis. Zang-Fu single pattern differentiation was considered successful in two situations: 1) if the algorithm founded a single DH which explained simultaneously all collected manifestations (F%=100%); or 2) if there was one pattern among DHs with a highest and unique F%. Otherwise, if multiple DHs were founded with equal values of F%, the procedure was unsuccessful since differentiation among competing Zang-Fu patterns was not possible. Hence, the algorithm displayed the message "Pattern differentiation was not possible with the provided information." In this case, physicians have access to the DH list and may want to revise the collected manifestations, continue examination of the patient to search for other manifestations, or replace the collected symptoms and signs with more specific ones. For instance, consider the following collected manifestations: "red face" and "irritability". Combinatorial database search yielded the following candidate patterns with respective F%: "liver-fire blazing upwards" (F%=100%), "liver-yang rising" (F%=50%), and "heart-fire blazing" (F%=50%). Since there was a unique candidate pattern which fully described the manifestations, and such pattern was selected as the diagnosis.
2.2   TCM pattern database   A textbook
23 was consulted to obtain data from which the pattern differentiation was implemented and tested. Sixty-nine patterns (Table 1) were described and all manifestations of each pattern were listed separately according to the FMs (Figure 1).
    

Table 1   Sixty-nine Zang-Fu single patterns

Single pattern

Single pattern

1. Deficiency-cold in the bladder

36. Phlegm-fluids obstructing the lungs

2. Kidney-qi deficiency

37. Heart-yang deficiency

3. Cold invading the large intestine

38. Phlegm-heat obstructing the lungs

4. Large intestine dryness

39. Heart-yin deficiency

5. Cold invading the stomach

40. Retention of food in the stomach

6. Liver-blood deficiency

41. Heat in the large intestine

7. Collapse of the large intestine

42. Deficiency-cold in the small intestine

8. Liver-blood stasis

43. Heat obstructing the large intestine

9. Damp-cold in the bladder

44. Small intestine qi pain

10. Liver-fire blazing upwards

45. Infestation of worms in the small intestine

11. Damp-cold invading the spleen

46. Small intestine qi tied

12. Liver-qi stagnation

47. Invasion of the large intestine by cold

13. Damp-heat in the liver and gall-bladder

48. Spleen not controlling blood

14. Liver-wind agitating within, deficient liver-blood causing wind

49. Invasion of the lungs by wind-cold

15. Damp-heat in the bladder

50. Spleen-qi deficiency

16. Liver-wind agitating within, extreme heat generating wind

51. Invasion of the lungs by wind-heat

17. Damp-heat in the gall-bladder

52. Spleen-qi sinking

18. Liver-wind agitating within, liver-yang rising causing wind

53. Invasion of the lungs by wind-water

19. Damp-heat in the large intestine

54. Spleen-yang deficiency

20. Liver-yang rising

55. Kidney-essence deficiency

21. Damp-heat invading the spleen

56. Stagnation of cold in the liver channel

22. Liver-yin deficiency

57. Kidney-qi not firm

23. Full-heat in the small intestine

58. Stasis of blood in the stomach

24. Lung dryness

59. Kidneys failing to receive qi

25. Gall-bladder deficiency

60. Deficiency-cold in the stomach

26. Lung-qi deficiency

61. Kidney-yang deficiency

27. Heart-blood deficiency

62. Stomach-fire

28. Lung-yin deficiency

63. Kidney-yang deficiency, water overflowing to the heart

29. Heart-blood stasis

64. Stomach-qi deficiency

30. Phlegm misting the mind

65. Kidney-yang deficiency, water overflowing to the lungs

31. Heart-fire blazing

66. Stomach-qi rebelling upwards

32. Phlegm-damp obstructing the lungs

67. Kidney-yin deficiency

33. Heart-qi deficiency

68. Stomach-yin deficiency

34. Phlegm-fire harassing the heart 69. Kidney-yin deficiency, empty-fire
35. Heart-yang collapse


   The complete database with patterns and manifestations grouped by the FMs was available upon request to the authors in Portuguese. Special attention was given to attribute the most specific description for each manifestation (e.g., ocular headache instead of headache). Five hundred and four manifestations were distributed among inspection (n=108, 21%), auscultation and olfaction (n=36, 7%), inquiry (n=335, 66%), and palpation (n=25, 6%). Patterns in the database are mutually exclusive and collectively exhaustive
24, i. e., for each manifestation there is at least one possible pattern, and there is no pattern without manifestations.
2.3
   Validation of the Zang-Fu single pattern differentiation method   The validity of the method was tested by sampling manifestations from the patterns to generate manifestation profiles to which the algorithm was applied. True positive (TP) cases were simulated by selection of a pattern from knowledge database and sort a variable count (0-100%) of its manifestations from all FMs, each chosen with equal probability. To generate true negatives (TN), the pattern selected as TP (and its description) was excluded from the database and the absolute count of manifestations—used to create the TP—was selected over all database patterns. Hence, both TP and TN present the same count of manifestations. Seven runs of simulations were performed according to individual or combined exam methods:
   1) Inspection
   2) Auscultation and olfaction
   3) Inquiry
   4) Palpation
   5) Inspection, auscultation and olfaction
   6) Inspection, auscultation and olfaction, inquiry
   7) Inspection, auscultation and olfaction, inquiry, palpation
   Two hundred manifestation profiles were generated (100 for TP and TN, respectively) for the 69 patterns, summing up 13 800 realizations per run. Globally, 96 600 cases were simulated and tested.
   The simulation algorithm outputs for each manifestation profile: 1) the simulated pattern; 2) NE; 3) NP; 4) F%; 5) the manifestation profiles in quoted phrases; and 6) the classification code for TP (=1) and TN (=0). The diagnostic algorithm receives item "5" and outputs for each tested profile: 1) the identified diagnosis; and 2) NDH. The comparison between the simulated pattern and the identified diagnosis yielded the binary classification of the proposed method for pattern differentiation (simulated=identified: successful =1; simulated≠identified: unsuccessful=0).
2.4
   Statistical analysis   Accuracy (proportion of true results in the population), sensitivity (probability that the test is positive given that the patient is sick), specificity (probability that the test is negative given that the patient is not sick), positive and negative predictive values (proportion of true positives and true negatives out of all positive results, respectively) were obtained from confusion matrices made from classification of simulated and identified diagnosis 20, 25. All algorithms were implemented in LabVIEWTM 8.0 (National Instruments) for Windows XP (Microsoft Corporation).

  

3   Results
   Accuracy, sensitivity, specificity, positive and negative predictive values are presented in Table 2 for each run of validation test. It can be observed that the highest accuracy was obtained with the inquiry (89.7%), followed by inspection (70.7%), auscultation and olfaction (59.9%), and palpation method (56.1%). Similar sequences were found for sensitivity and negative predictive value. However, specificity and positive predictive value were almost equal among individual exam methods.
   Combination of exam methods provided the highest accuracy, sensitivity, and negative predictive value while sustained high specificity and positive predictive value. The FMs presented the higher performance compared to combination of two or three exam methods as well as all single exam methods.
    

Table 2   Statistical performance of the method for single pattern differentiation according to Zang-Fu theory 

Diagnosis method

Accuracy

Sensitivity

Specificity

Negative predictive value

Positive predictive value

Single method

 

 

 

 

 

  A. Inspection

70.7%

41.5%

99.9%

63.1%

99.8%

  B. Auscultation and olfaction

59.9%

19.8%

100.0%

55.5%

99.8%

  C. Inquiry

89.7%

79.4%

99.9%

82.9%

99.9%

  D. Palpation

56.1%

12.3%

99.9%

53.2%

99.4%

Combined method

 

 

 

 

 

  Method A

70.7%

41.5%

99.9%

63.1%

99.8%

  Methods A+B

74.3%

48.7%

99.8%

66.1%

99.7%

  Methods A+B+C

92.0%

84.1%

99.9%

86.3%

99.9%

  Methods A+B+C+D

93.2%

86.5%

99.9%

88.1%

99.8%

 

  

4   Discussion
   This study presented the statistical performance of a method to differentiate among Zang-Fu single patterns. The method is computationally implemented and can be used by TCM doctors to assess the health status of a subject. The major contributions of this work comprise: 1) it was demonstrated that TCM Zang-Fu single pattern differentiation is possible with an accuracy up to 93.2%, and sensitivity and specificity of 86.5% and 99.9%, respectively; 2) results provided statistical data related to the classical description of "superior", "mediocre", and "inferior" TCM doctors; 3) generation of manifestation profiles is a simple tool that can be used to assess statistical estimators of TCM diagnostic methods.
   As anticipated in classic literatures4-8, this study showed that individual exam methods provide overall performance (accuracy, sensitivity, and specificity) of "inferior doctors". Chiu et al12 obtained recognition rate of 87.5% for blood stasis on tongue inspection using image processing techniques. Wang et al1 reported 88% as the highest accuracy in pattern differentiation using self-learning expert systems. Our results presented an accuracy of 93.2% using simple strategies to identify Zang-Fu single patterns. Although individual exam methods presented low accuracy and sensitivity in this study, their combination could increase the statistical performance of the classifier. Manifestations are closely related to the interdependent internal organs; thus, combined exam methods are preferable since they cover several forms of presentation of the same pattern. As stated before, current trends in TCM focus on computer aid to perform diagnosis1, 3, 14-17 and treatment2. It is believed that the combination of traditional methods and modern resources may improve the efficacy of TCM intervention.
  The initial screening tests should have high sensitivity, and final confirmatory tests must have high specificity
20. Full-text search is limited by the false positive problem (retrieve of irrelevant options) and low precision (natural language ambiguities). The use of a controlled vocabulary from knowledge database eliminates ambiguity, but can fail to recall relevant options. The use of quoted phrase searches can increase the recall of hypothesis. A limitation to diagnostic algorithms is that the user must possess a certain level of knowledge to discriminate or interpret the patient's complains 24. However, a controlled vocabulary ensures that every one is using the same terms to mean the same attribute. Structured diagnostic interviews are superior to open clinical interviews in deriving diagnosis because they facilitate manifestation reporting while systematically probing manifestations that physician may overlook, hence reducing variability. Although we used a single textbook to compile information about patterns, the validation method still can be used for assessing diagnostic power of other databases. This aspect reinforces the need for internationally available TCM ontology and web-based knowledge databases 3.
   Yang et al14 pointed out that TCM diagnosis can be improved with expert knowledge. The proposed single pattern differentiation method was built in a form of open base, in which new information could be added (or modified) to the knowledge database to increase statistical performance of the criterion. As a corollary, the proposed methodology relies on human experts, not only to select the knowledge, but also to provide the database organization. This issue can be diminished adding modules for knowledge discovery in database2.
   The diagnosis is based on every entry of the exam, and missing values are ignored for determination of TP since manifestations are considered Boolean variables (present/absent). Feng et al2 stated that all subjective symptoms should not always be taken into consideration simultaneously, suggesting the need for proper methods of selection. This idea was opposite to the assumption that a diagnosis must explain all patients' manifestations. Although the results clearly suggests that manifestations present considerable information for single pattern differentiation despite intensity or frequency of manifestations, the statistical performance may be increased by adding such information.
   Studies on TCM diagnosis accuracy often use data from population samples. This method presents a drawback since the real diagnosis is not known and samples may be biased (hospital patients, community subjects, etc.). The simulation of cases fixes both issues by randomly selecting manifestations only from the selected single pattern. However, manifestations may be sampled multiple times within the same run, resulting in less variation of manifestation profiles than it would be expected to see in real patients. Manifestations may not be chosen at all, resulting in untested data. We believe that the large simulated dataset would diminish these limitations.
   The major limitation of the proposed model is that it was tested only for Zang-Fu single patterns. Such case is the simplest one found in clinical practice for Zang-Fu pattern since the pathological process just begun to promote changes in homeostasis. The same subject may present several patterns simultaneously that are not mutually exclusive. Additionally, common etiologies and pattern transmissions among Zang-Fu—which also implies in determination of root-manifestation relationship—are contributing factors to limit the model's performance. Finally, other theories are often used to perform diagnosis (five phases, eight principles, vital substances, six channels, four levels, three-jiao) 23. Further improvements in the model should consider the above-cited aspects to extend its application in general clinical practice.
   The clinical implications of this work include the standardization of the whole TCM process in health care. Uniform descriptions of Zang-Fu single patterns in databases establish a routine in patients' examination, hence increasing diagnostic accuracy. Also, the application of objective rules for diagnosing may also help diminish diagnosis variability 26, 27 depending on the TCM physicians' expertise. The proposed model of diagnosing may be used as a software tool for real-time assessment of patients. Finally, standardization of treatment prescription is possible since well-defined diagnosis can be achieved.

 5   Conclusion
   This work presented a method for Zang-Fu single pattern differentiation. The method was validated with manifestation profiles providing statistical evidence of its diagnostic performance. This method can be used to aid TCM physicians in making single pattern diagnosis according to Zang-Fu theory.

  
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