Study protocol: Traditional Chinese Medicine (TCM) syndrome differentiation for heart failure patients and its implication for long-term therapeutic outcomes of the Qiliqiangxin capsules

Background Syndrome differentiation is a commonly used methodology and practice in Traditional Chinese Medicine (TCM) guiding the diagnosis and treatment of diseases including heart failure (HF). However, previous clinical trials seldom consider the impact of syndrome patterns on the outcome evaluation of TCM formulae. Qiliqiangxin (QLQX) capsule is a TCM formula with cardiotonic effect to improve the cardiovascular function for heart failure with proven efficacy from well-designed clinical trials. Though, there is no clinical trial with a large sample size and long assessment period that considers the relationship between TCM syndrome differentiation and the treatment efficacy of QLQX. In the present study, we design a study protocol to evaluate the relationship between TCM syndrome differentiation and the severity of heart failure as well as its progression. Furthermore, we will evaluate the impact of the TCM syndrome patterns on the efficacy of QLQX in the outcome of heart failure. Methods This is a clinical study conducted in conjunction with an ongoing clinical trial (QUEST Study) by sharing the parent patient populations but with different aims and independent designed roadmaps to investigate the TCM syndrome pattern distributions and the impacts of syndrome pattern types on the efficacy of QLQX in HF treatment. The clinical trial involves over 100 hospitals in mainland China and Hong Kong SAR with 3080 HF patients. By assessing the morbidity and re-hospitalization, we will verify and apply a modified TCM Questionnaire to collect the clinical manifestations of HF and acquire the tongue images of the patients to facilitate the syndrome differentiation. We will base on the “2014 Consensus from TCM experts on diagnosis and treatment of chronic heart failure” to evaluate the TCM syndromes for the patients. A pilot study with at least 600 patients will be conducted to evaluate the reliability, feasibility and validity of the modified TCM questionnaire for syndrome differentiation of HF and the sample size is calculated based on the confidence level of 95%, population size of 3080 and 5% margin of error. Secondly, we will investigate the characteristic of TCM syndrome distribution of HF patients and its correlation with the functional and biochemical data. Furthermore, we will evaluate the relationship between the TCM syndrome patterns and the efficacy of QLQX in the treatment of heart failure. Lastly, we will investigate the implication of tongue diagnosis in the severity and therapeutic outcome of HF. Expect outcomes To our knowledge, this is the first large scale clinical trial to evaluate the impacts of TCM syndrome differentiation on the progression and therapeutic outcome of HF patients and explore the diagnostic value of TCM Tongue Diagnosis in HF patients. We expect to obtain direct clinical evidence to verify the importance of TCM syndrome differentiation for the diagnosis and treatment of HF. Trial Registration: The trial was registered at Chinese Clinical Trial Registry, http://www.chictr.org.cn. (Registration No.: ChiCTR1900021929); Date: 2019-03-16.

Study Protocol: Traditional Chinese Medicine (TCM) Syndrome Differentiation for Heart Failure patients and its Implication for Long-term Therapeutic Outcome of Qiliqiangxin Capsules

BackgroundSyndrome differentiation is a commonly used methodology and practice in Traditional Chinese Medicine (TCM) guiding the diagnosis and treatment of diseases including heart failure (HF). However, previous clinical trials seldom consider the impact of syndrome patterns on the outcome evaluation of TCM formulae. Qiliqiangxin (QLQX) capsule is a TCM formula with cardiotonic effect to improve the cardiovascular function for heart failure with proven efficacy from well-designed clinical trials. Though, there is no clinical trial with a large sample size and long assessment period that considers the relationship between TCM syndrome differentiation and the treatment efficacy of QLQX. In the present study, we design a study protocol to evaluate the relationship between TCM syndrome differentiation and the severity of heart failure as well as its progression. Furthermore, we will evaluate the impact of the TCM syndrome patterns on the efficacy of QLQX in the outcome of heart failure. MethodsThis is a clinical study conducted in conjunction with an ongoing clinical trial (QUEST Study 1 ) to evaluate the efficacy of QLQX to improve the outcome of HF treatment through the assessment of morbidity and re-hospitalization, which involves over 100 hospitals in mainland China and Hong Kong SAR with 3,080 HF patients. Firstly, we will apply a modified TCM Questionnaire to collect the clinical manifestations of HF and acquire the tongue images of the patients to facilitate the syndrome differentiation. We will base on the “2014 Consensus from TCM experts on diagnosis and treatment of chronic heart failure” to evaluate the TCM syndromes for the patients. Secondly, we will investigate the characteristic of TCM syndrome distribution of HF patients and its correlation with the functional and biochemical data. Furthermore, we will evaluate the relationship between the TCM syndrome patterns and the efficacy of QLQX in the treatment of heart failure. Lastly, we will investigate the implication of tongue diagnosis in the severity and therapeutic outcome of HF. Expect OutcomesTo our knowledge, this will be the latest and well-designed clinical trial to evaluate the rules of TCM syndrome differentiation in the progression and therapeutic outcome of HF patients. We expect to obtain direct clinical evidence to verify the importance of TCM syndrome differentiation for the diagnosis and treatment of HF.Trial Registration1The trial was registered at Chinese Clinical Trial Registry, http://www.chictr.org.cn. (Registration No.: ChiCTR1900021929); Date: 2019-03-16.

Pain syndrome patterns and their characteristics in multiple sclerosis patients

Aim of the research is to analyze the patterns of pain syndromes and their characteristics in multiple sclerosis patients. Materials and Methods. A total of 104 multiple sclerosis patients complaining of pain during the last month were examined in Lviv Regional Multiple Sclerosis Center. We analyzed medical records, performed general medical and neurological examinations and compiled history of lifestyle, illness and pain. The VAS and PainDetect questionnaires were used to assess the characteristics of pain syndromes. The patients were asked to choose one of the 4 typical patterns of pain, which best described their feelings. Then the analysis of pain syndrome patterns and their characteristics was carried out. Results and Discussions. All 4 typical patterns of pain syndromes were registered in multiple sclerosis patients. However, only 26.92% of the participants experienced an intermittent pain pattern. The rest of patients suffered from patterns characterized by persistent pain. The evaluation of the patterns and their characteristics revealed typical features. The highest intensity of the severest and average pain during the last month was present in the patients suffering from constant pain with distinct attacks: 8.0 [7.0; 9.0] points (p<0.05) and 7.0 [5.0; 8.0] points (p<0.05), respectively. Persistent paroxysmal pain was more common in the multiple sclerosis patients with neuropathic pain (43.8±8.8% vs 20.4±5.8%, p<0.05). Irradiating pain is also characteristic to this pattern in 52.9±8.6% of patients (p<0.05). The head is the most common pain localization in the patients experiencing persistent pain with severe attacks - 82.4±9.2% of cases (p<0.05). Conclusions. Pain is a permanent symptom in a significant number of multiple sclerosis patients. It can have different patterns of progression. However, it has typical characteristics and their understanding will aid in the diagnosis, prognosis and treatment of pain syndromes in multiple sclerosis patients

Brain Functional Differences in Drug-Naive Major Depression with Anxiety Patients of Different Traditional Chinese Medicine Syndrome Patterns: A Resting-State fMRI Study

Major depressive disorder (MDD), especially combined with anxiety, has a high incidence and low detection rate in China. Literature has shown that patients under major depression with anxiety (MDA) are more likely to nominate a somatic, rather than psychological, symptom as their presenting complaint. In the theory of Traditional Chinese Medicine (TCM), clinical symptoms of MDD patients are mainly categorized into two different syndrome patterns: Deficiency and Excess. We intend to use resting-state functional magnetic resonance imaging (rs-fMRI) to investigate their brain functional differences and hopefully to find their brain function mechanism. For our research, 42 drug-naive MDA patients were divided into two groups (21 for Deficiency and 21 for Excess), with an additional 19 unaffected participants in the normal control (NC) group. We took Hamilton Depression Rating Scale (HAMD), Hamilton Anxiety Scale (HAMA), and brain fMRI scan for each group and analyzed the data. We first used Degree Centrality (DC) to map the functional differences in brain regions, utilized these regions as seed points, and used a seed-based functional connectivity (FC) analysis to identify the specific functional connection between groups. The Deficiency group was found to have higher HAMD scores, HAMA scores, and HAMD somatic factor than the Excess group. In the DC analysis, significant decreases were found in the right precuneus of both the Deficiency and Excess groups compared to the NC group. In the FC analysis, the right precuneus showed significant decreased network connectivity with the bilateral cuneus, as well as the right lingual gyrus in the Deficiency group when compared to the NC group and the Excess group. Through our research, it was found that precuneus dysfunction may have a relationship with MDA and Deficiency patients have more severe physical and emotional symptoms, and we realized that a larger sample size and multiple brain mode observations were needed in further research.

Investigation and Analysis on Constitution and Syndrome Types of HighNormal Blood Pressure People in Hebei Area in the Year of 2017

Purpose: To investigate the distribution of population and syndrome patterns in high-normal blood pressure people in Hebei area. Methods: A total of 453 people who met the inclusion criteria were investigated using a high-normal blood pressure human mass survey questionnaire. Results: of the 453 constitution types of high-normal blood pressure patients in Hebei area, 184were the constitution of yin-yang harmony, accounting for 40.62% of the total; 73 were the constitution of yang asthenia, accounting for 16.11% of the total; 59 were the constitution of damp-heat, accounting for 13.02% of the total; 52 were the constitution of qi asthenia, accounting for 11.48% of the total; 8 were the allergic constitution, accounting for 1.77% of the total. In addition, of their syndrome types, the syndrome of liver-fre hyperactivity were accounting for 30.24%; the syndrome of excessive phlegm-dampnesswere accounting for 26.71%; the syndrome of yin-defciency and yang-predominance were accounting for 23.18%; the syndrome of defciency of both yin and yang were accounting for 19.87%. Conclusion: Among the high-normal blood pressure people in Hebei area, the proportion of the constitution of yin-yang harmony is the highest, followed by the constitution of yang asthenia, the constitution of damp-heat, and the constitution of qi asthenia, with the lowest percentage being the allergic constitution. In addition, when it comes to the syndrome of them, the proportion of the syndrome of liver-fre hyperactivity is the highest, followed by the syndrome of yin-defciency and yang-predominance, and the lowest is the syndrome of defciency of both yin and yang.