A multi-center cross-sectional study of Chinese Herbal Medicine-Drug adverse reactions using active surveillance in Singapore's Traditional Chinese Medicine clinics.

BACKGROUND: This study aimed to investigate the rates and causality of patient-reported adverse events (AEs) associated with concomitant Chinese Herbal Medicine (CHM) and Western Medicine prescription drug (WMPD) consumption through active surveillance in Singapore's Traditional Chinese Medicine (TCM) clinics. METHODS: A cross-sectional study was conducted at five TCM clinics across Singapore from 8th May till 8th July 2023. Patients were screened to determine rates of CHM and WMPD consumption, and then interviewed if an AE was reported. An expert committee assessed the AE reports to determine causality. Along with descriptive statistics, odds ratios were calculated to determine AE occurrence likelihoods for patients who consumed both CHM and WMPD compared to CHM consumption alone. RESULTS: 1028 patients were screened and 62.65% of them reported concurrent CHM-WMPD consumption. Patients who consumed CHM and WMPD were 3.65 times more likely to experience an AE as compared to CHM consumption alone. 18 AE reports were adjudicated, with most AEs deemed unlikely due to CHM consumption. CONCLUSIONS: A large proportion of patients consumed CHM and WMPD concurrently, thus increasing their risk of experiencing AEs compared to those consuming CHM only. Active surveillance is applicable for detecting AEs, collecting data for causality assessment, and analysis.

Are Tai Chi and Qigong effective in the treatment of traumatic brain injury? A systematic review.

BACKGROUND: Traumatic brain injury (TBI) adversely affects both young and old and is a growing public health concern. The common functional, psychological, and cognitive changes associated with TBI and recent trends in its management, such as recommending sub-threshold aerobic activity, and multi-modal treatment strategies including vestibular rehabilitation, suggest that Tai Chi/Qigong could be beneficial for TBI. Tai Chi and Qigong are aerobic mind-body practices with known benefits for maintaining health and mitigating chronic disease. To date, no systematic review has been published assessing the safety and effectiveness of Tai Chi/Qigong for traumatic injury. METHODS: The following databases were searched: MEDLINE, CINAHL Cochrane Library, Embase, China National Knowledge Infrastructure Database, Wanfang Database, Chinese Scientific Journal Database, and Chinese Biomedical Literature Database. All people with mild, moderate, or severe TBI who were inpatients or outpatients were included. All Types of Tai Chi and Qigong, and all comparators, were included. All measured outcomes were included. A priori, we chose "return to usual activities" as the primary outcome measure as it was patient-oriented. Cochrane-based risk of bias assessments were conducted on all included trials. Quality of evidence was assessed using the grading of recommendation, assessment, development, and evaluation (GRADE) system. RESULTS: Five trials were assessed; three randomized controlled trials (RCTs) and two non-RCTs; only two trials were conducted in the last 5 years. No trial measured "return to normal activities" or vestibular status as an outcome. Four trials - two RCTs and two non-RCTS - all found Tai Chi improved functional, psychological and/or cognitive outcomes. One RCT had a low risk of bias and a high level of certainty; one had some concerns. One non-RCTs had a moderate risk of bias and the other a serious risk of bias. The one Qigong RCT found improved psychological outcomes. It had a low risk of bias and a moderate level of certainty. Only one trial reported on adverse events and found that none were experienced by either the exercise or control group. CONCLUSION: Based on the consistent finding of benefit in the four Tai Chi trials, including one RCT that had a high level of certainty, there is a sufficient signal to merit conducting a large, high quality multi-centre trial on Tai Chi for TBI and test it against current trends in TBI management. Based on the one RCT on TBI and Qigong, an additional confirmatory RCT is indicated. Further research is indicated that reflects current management strategies and includes adverse event documentation in both the intervention and control groups. However, these findings suggest that, in addition to Tai Chi's known health promotion and chronic disease mitigation benefits, its use for the treatment of injury, such as TBI, is potentially a new frontier. SYSTEMATIC REVIEW REGISTRATION: PROSPERO [ CRD42022364385 ].

Electro-acupuncture for central obesity: a patient-assessor blinded, randomized sham-controlled clinical trial.

BACKGROUND: Central obesity is considered as a significant health threat to individuals. Scientific research has demonstrated that intra-abdominal fat accumulation is associated with higher metabolic and cardiovascular disease risks independent of Body Mass Index (BMI). This study aimed to evaluate the efficacy and safety of electro-acupuncture in treating central obesity compared with sham acupuncture. METHOD: This was a patient-assessor blinded, randomized, sham-controlled clinical trial. One hundred sixty eight participants aged between 18 and 65 years old with BMI ≥ 25 kg/m2 and waist circumference (WC) of men ≥ 90 cm / women ≥ 80 cm were enrolled and allocated to the acupuncture or sham acupuncture group equally. For the acupuncture group, disposable acupuncture needles were inserted into eight body acupoints, including Tianshu (ST-25), Daheng (SP-15), Daimai (GB-26), Qihai (CV-6), Zhongwan (CV-12), Zusanli (ST-36), Fenglong (ST-40), and Sanyinjiao (SP-6) with electrical stimulation. For the control group, Streitberger's non-invasive acupuncture needles were utilized at the same acupoints with identical stimulation modalities. The treatment duration was 8 weeks with 2 sessions per week and the follow-up period was 8 weeks. The primary outcome was the change in WC before and after the treatment. The secondary outcomes were the changes in hip circumference, waist-to-hip circumference ratio, BMI, and body fat percentage during the treatment and follow-up period. RESULTS: The acupuncture group displayed a significant change in WC compared to the sham group both treatment and follow-up period (MD = -1.1 cm, 95% CI = -2.8 to 4.1). Significant change in body fat percentage was recorded for both groups after treatment but no significance was observed during the follow-up period (MD = -0.1%, 95% CI = -1.9 to 2.2). The changes in hip circumference were also significant both treatment and follow-up period for the acupuncture group (MD = -2.0 cm, 95% CI = -3.7 to -1.7). Compared with sham acupuncture, the body weight (MD = -1 kg, 95% CI = -3.3 to 5.3), BMI (MD = -0.5, 95% CI = -0.7 to 1.9) also decreased significantly within and between groups. The incidence of adverse events was similar in the two groups. CONCLUSION: This study provided evidence that electro-acupuncture could be effective in treating central obesity by reducing WC, hip circumference, body weight, BMI, and waist-to-hip circumference ratio. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03815253, Registered 24 Jan 2019.

Validation of the Cantonese version of the Traditional Chinese Medicine (TCM) Body constitution Questionnaire in elderly people.

BACKGROUND: The Traditional Chinese Medicine (TCM) Body Constitution Questionnaire (For Elderly People) (TCMECQ) is a patient-reported outcome questionnaire developed in Mandarin in 2013 to differentiate the body constitutions of the elderly aged 65 and above. Considering the cultural and linguistic differences between Mainland China and Hong Kong (HK) Special Administrative Region, the TCMECQ was translated into Cantonese following "back translation" policy and validated in proper process. METHODS: Ten Chinese Medicine Practitioners (CMPs) and 30 senior citizens aged 65 or above were recruited to evaluate the first version of the Traditional Chinese Medicine Body Constitution Questionnaire (For Elderly People) (Cantonese version) (TCMECQ-C). Based on their comments, the second version was developed and discussed in the panel meeting to form the third version, validated the third version on 270 recruited seniors. Based on the validation results, a panel of 5 experts finalized the Questionnaire as the final version. The TCMECQ-C developers finalized the Questionnaire as the validated endorsed third version (i.e. final version). RESULTS: The item-level content validity index of most items of the TCMECQ-C (First Version) were ranging from 0.80 to 1.00 in terms of clarity, relevance and appropriateness. Factor loadings of Qi-deficiency Constitution ranging from 0.37 to 0.71, Yang-deficiency Constitution ranging from 0.36 to 0.65, Yin-deficiency Constitution ranging from 0.36 to 0.65, and Stagnant Qi Constitution ranging from 0.68 to 0.82. The chi-squared degree-of-freedom ratio was 2.13 (928.63/436), Goodness-of-Fit Index (0.83), Adjusted Goodness-of-Fit Index (0.79), Normed Fit Index (0.66), Comparative Fit Index (0.78), Incremental Fit Index (0.78), Relative Fit Index (0.61) and Tucker-Lewis Index (0.75), and Root Mean Square Error of Approximation (0.07) and Standardized Root Mean Square Residual (0.07), implied acceptable Confirmatory Factor Analysis model fit of the overall scale. A Pearson correlation coefficient (r) showed the sufficient convergent validity for excessive subscales (Phlegm-dampness Constitution and Dampness-heat Constitution with r = 0.35, p < 0.01). Cronbach's alpha coefficient ranged from 0.56 to 0.89, including Qi-deficiency Constitution (0.67), Yang-deficiency Constitution (0.84), Yin-deficiency Constitution (0.59), Stagnant Blood Constitution (0.56), Stagnant Qi Constitution (0.89), Inherited Special Constitution (0.76) and Balanced Constitution (0.73), indicating acceptable internal consistency for subscales. The intra-class correlation coefficients of the TCMECQ-C ranged from 0.70 to 0.87 (p < 0.001), indicating moderate to good test-retest reliability. CONCLUSION: TCMECQ-C is a valid and reliable questionnaire for assessing the body constitution in Cantonese elderly.

Altered gut microbiota-host bile acid metabolism in IBS-D patients with liver depression and spleen deficiency pattern.

BACKGROUND: Dysregulation of gut microbiota-host bile acid (BA) co-metabolism is a critical pathogenic factor of diarrhea-predominant irritable bowel syndrome (IBS-D). Traditional Chinese Medicine (TCM), instructed by pattern differentiation, is effective in treating IBS-D, in which liver depression and spleen deficiency (LDSD) is the most prevalent pattern. Still, it is unclear the linkage between the LDSD pattern and the BA metabolic phenotype. PURPOSE: This study aimed to uncover the biological basis of the LDSD pattern from the BA metabolic perspective. METHODS: Patients with IBS-D completed questionnaires regarding the irritable bowel severity scoring system (IBS-SSS), stool frequency, Stool Bristol scale, and Self-Rating Scales of mental health. Fasting blood and morning feces were collected to analyze the gut metagenome and BA-related indices/metabolites. RESULTS: IBS-D patients with LDSD had a higher incidence of BA overexcretion (41% vs. 23% non-LDSD) with significant elevations in fecal total BAs and serum BA precursor 7α-hydroxy-4-cholesten-3-one levels. Compared to controls or non-LDSD patients, LDSD patients had a featured fecal BA profile, with higher proportions of deoxycholic acid (DCA), 7-ketodeoxycholic acid, and lithocholic acid. It is consistent with the BA-metabolizing genomic changes in the LDSD gut microbiota characterized by overabundances of 7-dehydroxylating bacteria and BA-inducible genes (baiCD/E/H). The score of bowel symptoms (stool frequency and abdominal pain) showing greater severity in the LDSD pattern were positively correlated with bai-expressing bacterial abundances and fecal DCA levels separately. CONCLUSION: We clarified a differed BA metabolic phenotype in IBS patients with LDSD, which closely correlates with the severity of bowel symptoms. It demonstrates that gut microbiota and host co-metabolism of BAs would provide crucial insight into the biology of the LDSD pattern and its internal relationship with IBS progression.

STandards for Reporting Interventions in Clinical Trials Of Tuina/Massage (STRICTOTM): Extending the CONSORT statement.

OBJECTIVES: Massage is a common therapy of nonpharmacological treatments, particularly in Tuina (Chinese massage) as its most common style, detailed guidance in reporting the intervention is warranted for its evaluation and replication. Based on the CONSORT (Consolidated Standards of Reporting Trials), we aimed to develop an Extension for Tuina/Massage, namely "The STandards for Reporting Interventions in Clinical Trials Of Tuina/Massage (STRICTOTM)." METHODS: A group of professional clinicians, trialists, methodologists, developers of reporting guidelines, epidemiologists, statisticians, and editors has developed this STRICTOTM checklist through a standard methodology process recommended by the EQUATOR (Enhancing the QUAlity and Transparency of Health Research) Network, including prospective registration, literature review, draft of the initial items, three rounds of the Delphi survey, consensus meeting, pilot test, and finalization of the guideline. RESULTS: A checklist of seven items (namely Tuina/Massage rationale, details of Tuina/Massage, intervention regimen, other components of the intervention, Tuina/Massage provider background, control or comparator interventions, and precaution measures), and 16 subitems were developed. Explanations and examples (E&E) for each item are also provided. CONCLUSIONS: The working group hopes that the STRICTOTM, in conjunction with both the CONSORT statement and extension for nonpharmacologic treatment, can improve the reporting quality and transparency of Tuina/Massage clinical research.

Are tai chi and qigong effective in the treatment of TBI? A systematic review protocol.

Background: Traumatic brain injury (TBI) adversely affects both young and old and is a growing public health issue. A number of recent trends in managing TBI, such as recommending sub-threshold aerobic activity, tailoring multi-modal treatment strategies, and studying the possible role of low-grade inflammation in those with persistent symptoms, all suggest that the physical and cognitive exercise of tai chi/qigong could have benefit. Method: Designed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, the following databases will be searched: MEDLINE, CINAHL, Cochrane Library, Embase, China National Knowledge Infrastructure Database, Wanfang Database, Chinese Scientific Journal Database, and Chinese Biomedical Literature Database. All clinical trials on mild, moderate and/or severe TBI with tai chi and/or qigong as the treatment group and any comparison group, in any setting will be included. Four reviewers will independently select studies; two reviewers for the English and two for the Chinese databases. Cochrane-based risk of bias assessments will be conducted on all included studies. An analysis will then be conducted with the grading of recommendation, assessment, development, and evaluation (GRADE) instrument. Results: This review will summarize the clinical trial evidence on tai chi/qigong for TBI including type of TBI, age/sex of participants, type and length of intervention and comparator, outcome measures, and any adverse events. The risk of bias will be considered, and the strengths and weaknesses of each trial will be analyzed. Discussion: The results of this review will be considered with respect to whether there is enough evidence of benefit to merit a more definitive randomized controlled trial.Systematic Review Registration: PROSPERO [CRD42022364385].

A framework on developing integrative medicine clinical practice guideline for stroke management and rehabilitation in Hong Kong.

BACKGROUND: Stroke is the second leading cause of death worldwide. In Hong Kong, the proportion of deaths caused by cerebrovascular disease accounted for approximately 6.8% of total deaths. Although integrative medicine approaches are widely adapted by patients, there is a lack of guideline to support the corresponding clinical practice for stroke management and rehabilitation. Therefore, we design this framework for the development of an integrative medicine clinical practice guideline (CPG) for stroke. METHODS: The framework follows the instructions of World Health Organization (WHO) handbook for guideline development, Guideline International Network (GIN), Appraisal of Guidelines for Research and Evaluation Instrument (AGREE II), and Reporting Items for Practice Guidelines in Healthcare (RIGHT). Three stages with ten steps are conducted. CONCLUSION: Clinical practice guidelines are essential to provide optimal recommendations for patients' prognosis. With proper methodology, this framework will facilitate the formation of clinical practice guideline for stroke through synthesizing evidences in the scope of integrative medicine.

Lingguizhugan Decoction, a Chinese herbal formula, improves insulin resistance in overweight/obese subjects with non-alcoholic fatty liver disease: a translational approach.

Lingguizhugan Decoction (LGZG) has been investigated in basic studies, with satisfactory effects on insulin resistance in non-alcoholic fatty liver disease (NAFLD). This translational approach aimed to explore the effect and underlying mechanism of LGZG in clinical setting. A randomized, double-blinded, placebo-controlled trial was performed. A total of 243 eligible participants with NAFLD were equally allocated to receive LGZG (two groups: standard dose and low dose) or placebo for 12 weeks on the basis of lifestyle modifications. The primary efficacy variable was homeostasis model assessment of insulin resistance (HOMA-IR). Analyses were performed in two populations in accordance with body mass index (BMI; overweight/obese, BMI ⩾ 24 kg/m2; lean, BMI < 24 kg/m2). For overweight/obese participants, low-dose LGZG significantly decreased their HOMA-IR level compared with placebo (-0.19 (1.47) versus 0.08 (1.99), P = 0.038). For lean subjects, neither dose of LGZG showed a superior effect compared with placebo. Methylated DNA immunoprecipitation sequencing and real-time qPCR found that the DNA N6-methyladenine modification levels of protein phosphatase 1 regulatory subunit 3A (PPP1R3A) and autophagy related 3 (ATG3) significantly increased after LGZG intervention in overweight/obese population. Low-dose LGZG effectively improved insulin resistance in overweight/obese subjects with NAFLD. The underlying mechanism may be related to the regulation of DNA N6-methyladenine modification of PPP1R3A and ATG3. Lean subjects may not be a targeted population for LGZG.

A pilot randomized placebo-controlled study on modified MaZiRenWan: a formulated Chinese medicine to relieve constipation for palliative cancer patients.

BACKGROUND: Constipation is a common problem among advanced cancer patients; however, many of them find limited effective from current therapies. Thus, we aimed to test the effect of a traditional Chinese herbal formula, modified MaZiRenWan (MZRW), by comparing with placebo among palliative cancer patients with constipation. METHODS: This is a randomized, double-blind, placebo-controlled trial. Participants aged over 18 were recruited and randomized to MZRW or placebo group in addition to current prescriptions (including ongoing laxatives treatment) for two weeks. Exclusion criteria included cognitive impairment, presence of a colostomy or gastrointestinal obstruction and estimated life expectancy of less than one month. Individualized modification of MZRW was allowed according to the traditional Chinese medicine (TCM) pattern of patient. The primary outcome was the global assessment of improvement, which reflected whether the constipation had improved, remained the same or worsened. RESULTS: Sixty patients, with mean age 75.2 years (range 47-95 years), were randomized to MZRW or placebo group. Among the MZRW group, 59.3% (16/27) had improvement in the global assessment score, as compared with 28.6% (8/28) of the placebo group (p-value = 0.022). Besides, the MZRW group had significant increase in stool frequency, and reduction in constipation severity and straining of defecation (p-value < 0.05). No serious adverse event was reported due to the research medication. CONCLUSION: This pilot trial suggests modified MZRW is well-tolerated and effective for relief of constipation in patients with advance cancer. It could be considered as a potential treatment option for constipation in palliative care. TRIAL REGISTRATION: The trial had been registered in ClinicalTrials.gov with identifier number NCT02795390 [ https://clinicaltrials.gov/ct2/show/NCT02795390 ] on June 10, 2016.

Chinese herbal medicine treatment based on subgroup differentiation as adjunct therapy for Parkinson's disease: study protocol of a pilot add-on, randomised, controlled, pragmatic clinical trial.

BACKGROUND: Parkinson's disease (PD) is a prevalent and debilitating condition. Conventional medications cannot control all symptoms and may inflict adverse effects. A survey reported that Chinese herbal medicine (CHM) is frequently sought. Existing CHM trials were contradictory and often of poor quality due to lack of methodological rigor. A national clinical guideline was drafted in China with diagnostic criteria and treatment strategy of Chinese medicine (CM) patterns subgroups of PD. The suggested CHM were found to exhibit neuroprotective effect in in vitro and in vivo studies. This trial aims to preliminarily assess the effect of CHM prescribed based on pattern differentiation on PD symptoms and patients' quality of life, and evaluate the feasibility of the trial design for a future large-scale trial. METHODS: This trial will be a pilot assessor- and data analyst blind, add-on, randomised, controlled, pragmatic clinical trial. 160 PD patients will be recruited and randomised into treatment or control groups in a 1:1 ratio. The trial will be conducted over 32 weeks. PD patients in the treatment group will be stratified into subgroups based on CM pattern and receive CHM accordingly in addition to conventional medication (ConM). The control group will receive ConM only. The primary outcome will be part II of the Movement Disorder Society Sponsored Revision of Unified Parkinson's Disease Rating Scale (MDS-UPDRS). Secondary outcomes will include part and total scores of MDS-UPDRS, domain and total scores of Non-motor symptom scale (NMSS). Adverse events will be monitored by monthly follow-ups and questionnaires. Mixed models will be used to analyse data by Jamovi and R. EXPECTED OUTCOMES: The success of our trial will show that the pragmatic design with subgroup differentiation is feasible and can produce reliable results. It will also provide preliminary data of the effect of CHM on improving clinical outcomes and quality of PD patients. Data collected will be used to optimize study design of the future large-scale clinical study. ETHICAL CLEARANCE: Ethical clearance of this study was given by the Research Ethics Committee of Hong Kong Baptist University (REC/20-21/0206). Trial registration This trial is registered on ClinicalTrials.gov (NCT05001217, Date: 8/10/2021, https://clinicaltrials.gov/ct2/show/NCT05001217 ). Type of manuscript: clinical trial protocol (date: 3rd November, 2021, version 1).

Sini San Inhibits Chronic Psychological Stress-Induced Breast Cancer Stemness by Suppressing Cortisol-Mediated GRP78 Activation.

Chronic psychological stress is closely correlated with breast cancer growth and metastasis. Sini San (SNS) formula is a classical prescription for relieving depression-related symptoms in traditional Chinese medicine (TCM). Current researches have suggested that chronic psychological stress is closely correlated with cancer stem cells (CSCs) and endoplasmic reticulum (ER) stress. This study aimed to investigate the effects of chronic psychological stress on ER stress-mediated breast cancer stemness and the therapeutic implication of SNS. Chronic psychological stress promoted lung metastasis in 4T1 breast tumor-bearing mice and increased the stem cell-like populations and stemness-related gene expression. Meanwhile, GRP78, a marker of ER stress, was significantly increased in the breast tumors and lung metastases under chronic psychological stress. As a biochemical hallmark of chronic psychological stress, cortisol dramatically enhanced the stem cell-like populations and mammospheres formation by activating GRP78 transcriptionally. However, GRP78 inhibitors or shRNA attenuated the stemness enhancement mediated by cortisol. Similarly, SNS inhibited chronic psychological stress-induced lung metastasis and stemness of breast cancer cells, as well as reversed cortisol-induced stem cell-like populations and mammospheres formation by attenuating GRP78 expression. Co-localization and co-immunoprecipitation experiments showed that SNS interrupted the interaction between GRP78 and LRP5 on the cell surface, thus inhibiting the Wnt/ß-catenin signaling of breast CSCs. Altogether, this study not only uncovers the biological influence and molecular mechanism of chronic psychological stress on breast CSCs but also highlights SNS as a promising strategy for relieving GRP78-induced breast cancer stemness via inhibiting GRP78 activation.

Efficacy and safety of Chinese medicine JCM-16021 for diarrhea-predominant irritable bowel syndrome: study protocol for a multi-center, randomized, double-blind, placebo controlled clinical trial.

BACKGROUND: Irritable bowel syndrome (IBS) is a common gastrointestinal functional disease. Adults with IBS may experience abdominal pain, change of bowel habits, and abnormal stool form without organic disease. IBS can seriously affect their work productivity and quality of life, especially diarrhea-predominant irritable bowel syndrome (IBS-D). The Chinese medicine JCM-16021 has been shown to be potentially effective in improving the symptoms of IBS-D based on a small scale clinical trial. Hence, a large scale clinical study is designed to further evaluate the efficacy and safety of the Chinese medicine JCM-16021 for IBS-D with traditional Chinese medicine (TCM) pattern of Liver Stagnation and Spleen Deficiency (LSSD). METHODS: This study is a multi-center, randomized, double-blind, placebo-controlled clinical trial. 392 eligible participants will be enrolled with 2-week run-in, 8-week treatment and 8-week follow-up. After run-in period, participants will be randomized to receive either the Chinese medicine JCM-16021 or placebo for 8 weeks, and will have post-treatment follow up for another 8 weeks. The primary outcome is the improvement rate on the global assessment of improvement (GAI) at week 10. The secondary outcomes consist of changes of IBS-D symptoms, TCM pattern improvement, IBS-Quality of Life (IBS-QoL), IBS-Symptom Severity Score (IBS-SSS), safety, etc. RESULTS: A standard protocol has been developed for the study. The protocol will provided a detailed procedure to conduct a clinical trial and verify if the Chinese medicine JCM-16021 would significantly improve the overall symptoms of IBS-D with LSSD pattern of TCM by relieving abdominal pain, reducing stool frequency, improving the stool consistency and improving quality of life. The consolidated evidence from the study can shed light on the treatment of IBS-D with Chinese medicine. CONCLUSION: The protocol will provide details for investigators about the study following SPIRIT Statement. High-quality evidence on the efficacy and safety of Chinese medicine JCM-16021 for IBS-D will be provided through strict compliance with the protocol. TRIAL REGISTRATION: ClinicalTrial.gov identifier: NCT03457324. Registered 8 February 2018, https://clinicaltrials.gov/ct2/show/NCT03457324?term=NCT03457324&draw=2&rank=1.

Electro-acupuncture for irritable bowel syndrome patients: study protocol for a single-blinded randomized sham-controlled clinical trial.

BACKGROUND: Irritable bowel syndrome (IBS) is one of the most common functional gastrointestinal disorders in clinical practice. IBS diagnosis is based on symptoms defined by abdominal pain or discomfort associated with defecation or changes in bowel habits. Gut-brain interaction caused by stress or depressive emotion is one of the essential pathologies. Acupuncture has been used for the treatment of internal medicine, including digestive disorders and depressive disorders in Chinese medicine. This study aims to determine whether electro-acupuncture could have significant benefits than sham acupuncture for IBS. METHODS/DESIGN: This is a single-blinded randomized sham-controlled clinical trial with two arms. A total of 120 IBS patients will be recruited. After a 2-week run-in period, eligible subjects will be randomly assigned to one of two arms, acupuncture (AC) arm and sham acupuncture (SAC) arm. Each eligible subject will go through a 2-week run-in-period, 6-week treatment period, and 6-week follow-up period. Five visits in total were scheduled for each subject in week 0, week 2, week 5, week 8, and week 14. The outcomes would be measured with (1) IBS-SSS, (2) Hamilton Depression Rating Scale (HAMD-17), (3) Clinical Global Impression-Severity (CGI-S), (4) Self-Rating Depression Scale (SDS), and (5) IBS Quality of Life (IBS-QoL). DISCUSSION: The study will compare electro-acupuncture with sham acupuncture to explore the feasibility of electro-acupuncture in improving IBS symptoms. TRIAL REGISTRATION: ClinicalTrials.gov NCT04387383 . Registered on 13 May 2020.

Electro-acupuncture for central obesity: randomized, patient-assessor blinded, sham-controlled clinical trial protocol.

BACKGROUND: Obesity is a common medical condition. Among all the classifications of obesity, central obesity is considered to be a significant threat on the health of individuals. Scientific researches have demonstrated that the accumulation of intra-abdominal fat is associated with higher metabolic and cardiovascular disease risks independently from Body Mass Index (BMI). Our previous research found that the combination of electro-acupuncture and auricular acupressure could significantly reduce the body weight and the BMI compared to sham control group. METHODS/DESIGN: This is a patient-assessor blinded, randomized, sham-controlled clinical trial on electro-acupuncture for central obesity. One hundred sixty-eight participants with central obesity will be randomly assigned to two groups, which are the acupuncture group and the sham control group. The whole study duration will be 8-week treatment plus 8-week follow up. The primary outcome is the change in waist circumference before and after the treatment. The secondary outcomes include the changes in hip circumference, waist-to-hip circumference ratio, BMI and body fat percentage during the treatment and follow-up. CONCLUSION: The trial will evaluate the efficacy and safety of electro-acupuncture for central obesity compared with sham acupuncture. The study may provide the solid evidence of electro-acupuncture on central obesity in Hong Kong. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03815253 ,Registered 24 Jan 2019.

COVID-19 Rehabilitation With Herbal Medicine and Cardiorespiratory Exercise: Protocol for a Clinical Study.

BACKGROUND: Recent studies have revealed that many discharged patients with COVID-19 experience ongoing symptoms months later. Rehabilitation interventions can help address the consequences of COVID-19, including medical, physical, cognitive, and psychological problems. To our knowledge, no studies have investigated the effects of rehabilitation following discharge from hospital for patients with COVID-19. OBJECTIVE: The specific aims of this project are to investigate the effects of a 12-week exercise program on pulmonary fibrosis in patients recovering from COVID-19. A further aim will be to examine how Chinese herbal medicines as well as the gut microbiome and its metabolites regulate immune function and possibly autoimmune deficiency in the rehabilitation process. METHODS: In this triple-blinded, randomized, parallel-group, controlled clinical trial, we will recruit adult patients with COVID-19 who have been discharged from hospital in Hong Kong and are experiencing impaired lung function and pulmonary function. A total of 172 eligible patients will be randomized into four equal groups: (1) cardiorespiratory exercise plus Chinese herbal medicines group, (2) cardiorespiratory exercise only group, (3) Chinese herbal medicines only group, and (4) waiting list group (in which participants will receive Chinese herbal medicines after 24 weeks). These treatments will be administered for 12 weeks, with a 12-week follow-up period. Primary outcomes include dyspnea, fatigue, lung function, pulmonary function, blood oxygen levels, immune function, blood coagulation, and related blood biochemistry. Measurements will be recorded prior to initiating the above treatments and repeated at the 13th and 25th weeks of the study. The primary analysis is aimed at comparing the outcomes between groups throughout the study period with an α level of .05 (two-tailed). RESULTS: The trial has been approved by the university ethics committee following the Declaration of Helsinki (approval number: REC/19-20/0504) in 2020. The trial has been recruiting patients. The data collection will be completed in 24 months, from January 1, 2021, to December 31, 2022. CONCLUSIONS: Given that COVID-19 and its sequelae would persist in human populations, important findings from this study would provide valuable insights into the mechanisms and processes of COVID-19 rehabilitation. TRIAL REGISTRATION: ClinicalTrials.gov NCT04572360; https://clinicaltrials.gov/ct2/show/NCT04572360. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): PRR1-10.2196/25556.

A Comparative Study for License Application Regulations on Proprietary Chinese Medicines in Hong Kong and Canada.

Ethnopharmacological Relevance: Chinese Medicine plays a symbolic role among traditional medicines. As Chinese Medicine products are widely used around the globe, regulations for Chinese Medicine products are often used as models for the efficient regulation of natural products that are safe, and high-quality. Aim of the Study: We aimed to compare the regulatory registration requirements for Proprietary Chinese Medicines in Hong Kong and Canada. Materials and Methods: We compared registration requirements for Proprietary Chinese Medicine in Hong Kong and Canada based on publicly available information provided by the respective Regulators. A marketed product, Zhizhu Kuanzhong Capsule (SFDA approval number Z20020003; NPN approval number 80104354), was used as a case study to demonstrate the similarities and differences of the requirements in both Hong Kong and Canada. Results: There were similarities and differences between the two regulatory systems in terms of the quality, safety and efficacy requirements. Despite the superficial appearance of similar categories and groups/classes, Hong Kong requires significantly more primary test data compared to Canada's reliance on attestation to manufacturing according the standards outlined in approved reference pharmacopeias/texts. Conclusion: Improved understand of the similarity and differences will enable applicants to plan appropriate strategies for gaining product approval. Exploring ways to harmonize the regulatory process has the potential to benefit manufacturers, regulators, and patients by increasing efficiency and decreasing costs.

Chinese medicine formulas for nonalcoholic fatty liver disease: Overview of systematic reviews.

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) affects more than one-quarter of the global population. Due to the lack of approved chemical agents, many patients seek treatment from traditional Chinese medicine (TCM) formulas. A variety of systematic reviews have been published regarding the effectiveness and safety of TCM formulas for NAFLD. AIM: To critically appraise available systematic reviews and sort out the high-quality evidence on TCM formulas for the management of NAFLD. METHODS: Seven databases were systematically searched from their inception to 28 February 2020. The search terms included "non-alcoholic fatty liver disease," "Chinese medicines," "systematic review," and their synonyms. Systematic reviews involving TCM formulas alone or in combination with conventional medications were included. The methodological quality and risk of bias of eligible systematic reviews were evaluated by using A Measure Tool to Assess Systematic Reviews 2 (AMSTAR 2) and Risk of Bias in Systematic Review (ROBIS). The quality of outcomes was assessed by the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system. RESULTS: Seven systematic reviews were ultimately included. All systematic reviews were conducted based on randomized controlled trials and published in the last decade. According to the AMSTAR 2 tool, one systematic review was judged as having a moderate confidence level, whereas the other studies were rated as having a low or extremely low level of confidence. The ROBIS tool showed that the included systematic reviews all had a high risk of bias due to insufficient consideration of identified concerns. According to the GRADE system, only two outcomes were determined as high quality; namely, TCM formulas with the HuoXueHuaYu principle were better than conventional medications in ultrasound improvement, and TCM formulas were superior to antioxidants in alanine aminotransferase normalization. Other outcomes were downgraded to lower levels, mainly because of heterogeneity among studies, not meeting optimal information sample size, and inclusion of excessive numbers of small sample studies. Nevertheless, the evidence quality of extracted outcomes should be further downgraded when applying to clinical practice due to indirectness. CONCLUSION: The quality of available systematic reviews was not satisfactory. Researchers should avoid repeatedly conducting systematic reviews in this area and focus on designing rigorous randomized controlled trials to support TCM formula applications.

Evidence-based Chinese Medicine Clinical Practice Guideline for Stroke in Hong Kong.

BACKGROUND: Stroke in Chinese Medicine (CM) includes the concepts of ischemic and hemorrhagic strokes from Western Medicine and is a common disease in Hong Kong. This clinical practice guideline (CPG) aims to evaluate and demonstrate CM treatment options for stroke, provide guideline for local CM practice, and act as a reference for decision makers on drafting CM related health policies. METHODS: Based on the principle of multidisciplinary integration and evidence-based medicine, a steering committee oversaw the CPG development process in accordance with a published protocol. Clinical questions and evidences were identified, appraised, and synthesised through systematic literature reviews, text mining, and two rounds of Delphi surveys with a multidisciplinary panel of experts. RESULTS: In this CPG, we defined stroke from the perspectives of both CM and Western Medicine, reported corresponding CM treatment options, and carried out evaluation based on levels of evidence and grade of recommendation. Suggested CM interventions include herbal medicine treatment based on pattern differentiation, acupuncture treatment, and nursing care. CONCLUSION: The target population is Hong Kong stroke patients with prodrome or sequela stage. This CPG is intended to help standardizing CM clinical practice and enhancing efficiency of clinical service in Hong Kong.

Modified Zhibai Dihuang pill, a traditional Chinese medicine formula, on steroid withdrawal in systemic lupus erythematosus: A systematic review and meta-analysis.

BACKGROUND: Zhibai Dihuang pill (ZBDH), a Chinese herbal formula, has been widely used as an adjunctive therapy to help reduce the patient's steroid dose and maintain low disease activity in systemic lupus erythematosus (SLE). OBJECTIVE: This systematic review evaluates the therapeutic effect of modified ZBDH in reducing steroid use in patients with SLE. SEARCH STRATEGY: A systematic literature search was carried out using seven databases, including PubMed, Embase, Cochrane Central Register of Controlled Trials, Chinese Biomedical Literature Database, Chinese National Knowledge Infrastructure, Chinese VIP Information and Wanfang Database, from their inception to June 1st, 2019. The search terms included "systemic lupus erythematosus," "Chinese medicine" and "clinical trial," and their synonyms. Subject headings matching the above terms were also used. INCLUSION CRITERIA: This meta-analysis included randomized controlled trials that evaluated the reduction of steroid dose in patients with SLE. Traditional Chinese medicine (TCM) formulas in experimental group should be prescribed based on ZBDH and used as adjunctive therapy and the comparator should contain steroids. DATA EXTRACTION AND ANALYSIS: Two authors independently conducted database search, study selection, data extraction and quality assessment. The extracted information contained study design, sample size, recruitment mode, diagnostic criteria, inclusion and exclusion criteria, participant characteristics, TCM patterns, TCM formulas and treatment outcomes. The primary outcome was the change of steroid dose. Secondary outcomes included SLE Disease Activity Index (SLEDAI), biomarkers of disease activity and clinical response rate. STATA 15.0 was used to analyze the pooled effects reported as weighted mean difference (WMD) or odds ratio, with a 95% confidence interval (CI). RESULTS: In total, 20 trials involving 1470 SLE patients were included. The pooled result showed that modified ZBDH taken in combination with standard care led to a larger reduction in steroid dose, compared to standard care alone (WMD: 3.79; 95% CI: 2.58-5.01; P < 0.001). Favorable outcomes were also seen in secondary outcome criteria, such as SLEDAI and complement 3. The modified ZBDH treatments were well tolerated without increasing adverse effects. CONCLUSION: The systematic review provided preliminary evidence supporting the use of ZBDH as a co-therapy to aid steroid dose reduction in patients with SLE. However, more rigorous studies should be conducted to validate these findings, and explore the mechanisms of ZBDH's relevant bioactive constituents.