| This paper includes the following three parts:qualitative research, diagnostic test, and pragmatic randomized controlled trial (PRCT).Objective1. Qualitative research:This research aimed at exploring the ideas and methods of professor Chen Ke-ji on pattern identification (PI) of blood stasis syndrome (BSS), and trying to establish a simplified and quantified diagnostic criterion of BSS.2. Diagnostic test:This research aimed at evaluating the reliability and validity of "simplified and quantified diagnostic criterion of BSS".3. PRCT:The aims of this research were to assess the effectiveness and safety of "Chen Ke-ji PI methods of BSS" in treating stable angina pectoris.Methods1. Qualitative researchOn the basis of literature review, semi-structure interviews were used to explore the ideas and methods of professor Chen Ke-ji on PI of BSS from professor Chen Ke-ji and his inheritors. Previous clinical medical records of professor Chen Ke-ji on the diagnosis and treatment of BSS were considered as supplements. Data were analyzed through thematic analysis method in RQDA software. According to the approach of triangulation, results of interviews were compared with analysis results of medical records, and contents in relevant literatures and books. During the study, reflexivity of researcher was implemented to improve the validity of results. Finally, in order to ensure the reliability of results, the whole results were fed back to professor Chen Ke-ji to check and revise. Additionally, on the basis of previous diagnosis criteria of BSS, combining with the experience of professor Chen Ke-ji in pattern identification, a simplified and quantified diagnostic criterion of BSS was tried to established.2. Diagnostic testAccording to three diagnostic criteria of BSS ("simplified and quantified diagnostic criterion of BSS (criterion A), "diagnostic criterion of BSS in 1986" (criterion B), "consensus of integrative medicine on BSS diagnosis in 2011" (criterion C)),712 patients from different departments in Xiyuan Hospital were investigated. Firstly, two researchers independently used criterion A to diagnose the same 112 patients in 14 different departments in Xiyuan Hospital, respectively. Secondly, two researchers independently used criterion A, criterion B and criterion C to diagnose 300 different patients in 15 department in Xiyuan Hospital (600 patients in total), respectively. The reliability of criterion A and its consistency with the other two criteria were calculated using the Kappa coefficient. A Bayesian approach was employed to assess the validity of criterion A.3. PRCTThis research is a pragmatic stratified randomized controlled trial.300 patients with stable angina pectoris met the inclusion criteria would be considered for enrollment. All eligible patients would be randomly assigned into two groups, and each group would have 150 patients. On the basis of Western conventional therapy and traditional Chinese medicine (TCM) conventional therapy, the treatment group was assigned to "Chen Ke-ji PI methods of BSS" -guided treatment. While, the control group was assigned to "conventional PI methods of BSS"-guided therapy. The effectiveness and safety of "Chen Ke-ji PI methods of BSS" in treating stable angina pectoris were evaluated according to the comparison within groups and between groups. The sensitivity of "simplified and quantified diagnostic criterion of BSS" was also examined. This analysis was interim analysis, just focusing on patients who had finished 4 weeks follow up from initiate to January 15,2015.Results1. Qualitative research4) "Chen Ke-ji PI methods of BSS"contained the following three themes: academic ideas, characteristics of PI, and foundations of PI. Of which, academic ideas included the following four sub-themes:"ten-principle PI", the combination of disease and syndrome, syndrome classified by disease, and the combination of macroscopic PI and microscopic PI. The characteristics of PI also consisted of four sub-themes as follows: "ten-BSS" theory; emphasizing the cause of disease; differentiating deficiency, excess, cold and heat at first; emphasizing tongue diagnosis and interrogation; emphasizing the relationship between viscera; differentiating the severity of syndrome; considering stages and types of disease; "blood stasis and toxin causing catastrophe" theory. The foundations of PI included two sub-themes that were TCM macro-index and laboratory examination.5) "Chen Ke-ji prescription of BSS", in the guidance of "Chen Ke-ji PI methods of BSS", included the following three themes:principle of prescriptions, characteristics of therapy, and characteristics of prescriptions. Of which, the principle of prescriptions consisted of seven sub-themes as follows:treatment based on the cause of disease; adjustments of prescriptions based on syndrome; changes of prescriptions in accordance with symptoms; emphasizing the combination of disease and syndrome; considering the severity of syndrome; considering special recipes for special diseases; considering manifestation and root cause of disease, and the degree of urgency. The characteristics of therapy comprised the following four sub-themes:regulating qi and activating blood; treating heart alone with stomach; three warming therapies, and two tonifying therapies; and other common therapies. The characteristics of prescriptions also included four sub-themes as follows:classifying herbs with effect on activating blood circulation; few herbs in a prescription; considering findings in studies; common prescriptions and herbs.6) "Simplified and quantified diagnostic criterion of BSS" consisted of eight primary criteria and ten secondary criteria.2. Diagnostic test1) Two researchers independently used criterion A to diagnose the same 112 patients, respectively. According to the consistency check, criterion A presented a good consistency when used by different researchers (diagnostic accordance rate was 91.96%, Kappa=0.82, P<0.001). Meanwhile, data from 600 patients showed that there was an acceptable diagnostic consistency among criterion A, criterion B and criterion C.2) According to Bayesian estimation, results from 600 patients suggested that criterion A had higher sensitivity but similar specificity, as compared with criterion B or criterion C. For example, compared with criterion B (the median of sensitivity and specificity were 0.762 (95% confidence interval (CI) 0.731 to 0.790) and 0.902 (95% CI 0.858 to 0.936), respectively), the median of sensitivity and specificity of criterion A were 0.911 (95% CI 0.888 to 0.930) and 0.875 (95% CI 0.826 to 0.915), respectively. The difference between criterion A and B, the median of sensitivity and specificity were 0.149 (95% CI:0.112,0.184) and -0.026 (95%CI:-0.085,0.033), respectively.3) According to Bayesian estimation, results from 600 patients showed that Youden index of criterion A is higher than that of criterion A and criterion B; positive likelihood ratios of the three criteria were all high, but had no statistically significant difference; negative likelihood ratios of the three criteria were low, and the ratio tendency was A< C< B; there was no statistically significant difference among the three criteria in positive predictive value and negative predictive value.3. PRCTThis analysis was interim analysis, just focusing on the 102 patients with stable angina pectoris who had finished 4 weeks follow up (51 patients in the treatment group and 51 patients in the control group). The results were as follows:1) During the 102 patients,78 were diagnosed with BSS according "simplified and quantified diagnostic criterion of BSS" and "conventional PI methods of BSS".24 patients (23.5%) were diagnosed with BSS according "simplified and quantified diagnostic criterion of BSS" other than "conventional PI methods of BSS". The BSS scores of the 24 patients had no statistically significant difference with that of the 78 patients at the enrollment time (Z=-1.404, P=0.160). Additionally,21 of the 24 patients (87.5%) had hyper-coagulation state, with one or more hemorheology indexes (except red blood cell deformation rate) beyond the range of normal value.2) On the basis of conventional therapy, patients in the treatment group, treated in the guidance of "Chen Ke-ji PI methods of BSS" for two weeks, had reduction in angina scores (Z=-3.619, P=0.000). Furthermore, after treatment for four weeks, patients in the treatment group had reduction in angina scores (Z=-5.166, P=0.000), BSS scores (Z=-4.855, P=0.000), the maximum agglutination of platelet(P=0.021,95% CI (0.77,8.86)), the adhesion rate of platelet (P=0.008), the blood viscosity (1.0s-1) (P=0.001,95% CI (0.82,3.22)), the blood viscosity (5.0s-’) (P=0.006, 95% CI (0.45,2.26)), the blood viscosity (10.0s-1) (P=0.009,95% CI (0.30,1.97)), and the blood viscosity (35.0s-1) (P=0.048,95% CI (0.00,1.14))3) On the basis of conventional therapy, patients in the treatment group, treated in the guidance of "Chen Ke-ji PI methods of BSS" for two weeks, had no increase in the use of nitroglycerin, and 23.5% of the 51 patients stopped or reduced the use of nitroglycerin. Furthermore, after treatment for four weeks, patients in the treatment group still had no increase in the use of nitroglycerin, and further 23.5% of the patients stopped or reduced the use of nitroglycerin.4) Compared with the control group, patients in the treatment group had more reduction in the adhesion rate of platelet after four weeks interventions (P=0.033). There was no difference in the improvement of BSS scores, angina scores, and the use of nitroglycerin (P>0.05) between the two groups. Nevertheless, patients in the treatment group had a tendency in the decrease of the BSS scores (P=0.079), which might be related to the limited sample size in this interim analysis.5) TCM added to Western conventional therapy in 102 patients with stable angina pectoris for four weeks showed no additional risk of bleeding.Conclusion1. Qualitative research1) "Chen Ke-ji PI methods of BSS" contained three contents including academic ideas, characteristics of PI, and foundations of PI. Of which, "Ten-principle PI", "ten-BSS" theory, and "blood stasis and toxin causing catastrophe" theory were the most highlights.2) "Chen Ke-ji prescription of BSS", in the guidance of "Chen Ke-ji PI methods of BSS", included seven principles, four characteristics of therapy, and four characteristics of prescriptions. Of which, "classifying herbs with effect on activating blood circulation", "regulating qi and activating blood", "three warming therapies, and two tonifying therapies" were the most highlights.3) "Simplified and quantified diagnostic criterion of BSS" consisted of eight primary criteria and ten secondary criteria.2. Diagnostic test1) Compared with "diagnostic criterion of BSS in 1986" and "consensus of integrative medicine on BSS diagnosis in 2011", "simplified and quantified diagnostic criterion of BSS" not only has good reliability, but also characterized by high sensitivity and nice specificity.2) Compared with "diagnostic criterion of BSS in 1986" and "consensus of integrative medicine on BSS diagnosis in 2011", "simplified and quantified diagnostic criterion of BSS" had higher veracity in the diagnosis of BSS.3) There were similar ability in the confirmation of BSS among "diagnostic criterion of BSS in 1986", "consensus of integrative medicine on BSS diagnosis in 2011", and "simplified and quantified diagnostic criterion of BSS". While, the last criterion was highlighted at the ability of the exclusion of BSS.3. PRCT1) "Simplified and quantified diagnostic criterion of BSS" was more sensitivity than "conventional PI methods of BSS". Thus, "simplified and quantified diagnostic criterion of BSS" was good for the diagnosis and treatment of BSS in early stage.2) Treatment in the guidance of "Chen Ke-ji PI methods of BSS" added to conventional therapy in patients with stable angina pectoris could improve BSS and symptom of angina, reduce the use of nitroglycerin, decrease the maximum agglutination of platelet, the adhesion rate of platelet and the blood viscosity, with no additional risk of bleeding.3) Compared with treatment in the guidance of "conventional PI methods of BSS", patients treated in the guidance of "Chen Ke-ji PI methods of BSS" had more decrease in the adhesion rate of platelet. There were similar effects on the improvement of BSS and angina between the two kinds of treatments. |
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