Quantification of prevalence, clinical characteristics, co-existence, and geographic variations of traditional Chinese medicine diagnostic patterns via latent tree analysis-based differentiation rules among functional dyspepsia patients.

BACKGROUND: Traditional Chinese Medicine (TCM) treatment strategies are guided by pattern differentiation, as documented in the eleventh edition of the International Classification of Diseases (ICD). However, no standards for pattern differentiation are proposed to ensure inter-rater agreement. Without standardisation, research on associations between TCM diagnostic patterns, clinical features, and geographical characteristics is also not feasible. This diagnostic cross-sectional study aimed to (i) establish the pattern differentiation rules of functional dyspepsia (FD) using latent tree analysis (LTA); (ii) compare the prevalence of diagnostic patterns in Hong Kong and Hunan; (iii) discover the co-existence of diagnostic patterns; and (iv) reveal the associations between diagnostic patterns and FD common comorbidities. METHODS: A total of 250 and 150 participants with FD consecutively sampled in Hong Kong and Hunan, respectively, completed a questionnaire on TCM clinical features. LTA was performed to reveal TCM diagnostic patterns of FD and derive relevant pattern differentiation rules. Multivariate regression analyses were performed to quantify correlations between different diagnostic patterns and between diagnostic patterns and clinical and geographical variables. RESULTS: At least one TCM diagnostic pattern was differentiated in 70.7%, 73.6%, and 64.0% of the participants in the overall (n = 400), Hong Kong (n = 250), and Hunan (n = 150) samples, respectively, using the eight pattern differentiation rules derived. 52.7% to 59.6% of the participants were diagnosed with two or more diagnostic patterns. Cold-heat complex (59.8%) and spleen-stomach dampness-heat (77.1%) were the most prevalent diagnostic patterns in Hong Kong and Hunan, respectively. Spleen-stomach deficiency cold was highly likely to co-exist with spleen-stomach qi deficiency (adjusted odds ratio (AOR): 53.23; 95% confidence interval (CI): 21.77 to 130.16). Participants with severe anxiety tended to have liver qi invading the stomach (AOR: 1.20; 95% CI: 1.08 to 1.33). CONCLUSIONS: Future updates of the ICD, textbooks, and guidelines should emphasise the importance of clinical and geographical variations in TCM diagnosis. Location-specific pattern differentiation rules should be derived from local data using LTA. In future, patients' pattern differentiation results, local prevalence of TCM diagnostic patterns, and corresponding TCM treatment choices should be accessible to practitioners on online clinical decision support systems to streamline service delivery.

Methodological quality of systematic reviews on Chinese herbal medicine: a methodological survey.

BACKGROUND: Systematic reviews (SRs) synthesise the best evidence of effectiveness and safety on Chinese herbal medicine (CHM). Decision-making should be supported by the high-quality evidence of prudently conducted SRs, but the trustworthiness of conclusions may be limited by poor methodological rigour. METHODS: This survey aimed to examine the methodological quality of a representative sample of SRs on CHM published during January 2018 to March 2020. We conducted literature search in Cochrane Database of Systematic Reviews, MEDLINE via Ovid, and EMBASE via Ovid. Eligible SRs must be in Chinese or English with at least one meta-analysis on the treatment effect of any CHM documented in the 2015 Chinese Pharmacopoeia. Two reviewers extracted the bibliographical characteristics of SRs and appraised their methodological quality using AMSTAR 2 (Assessing the Methodological Quality of Systematic Reviews 2). The associations between bibliographical characteristics and methodological quality were investigated using Kruskal-Wallis tests and Spearman's rank correlation coefficients. RESULTS: We sampled and appraised one hundred forty-eight SRs. Overall, one (0.7%) was of high methodological quality; zero (0%), four (2.7%), and one-hundred forty-three (96.6%) SRs were of moderate, low, and critically-low quality. Only thirteen SRs (8.8%) provided a pre-defined protocol; none (0%) provided justifications for including particular primary study designs; six (4.1%) conducted a comprehensive literature search; two (1.4%) provided a list of excluded studies; nine (6.1%) undertook meta-analysis with appropriate methods; and seven (4.7%) reported funding sources of included primary studies. Cochrane reviews had higher overall quality than non-Cochrane reviews (P < 0.001). SRs with European funding support were less likely to have critically-low quality when compared with their counterparts (P = 0.020). SRs conducted by more authors (rs = 0.23; P = 0.006) and published in higher impact factor journals (rs = 0.20; P = 0.044) were associated with higher methodological quality. CONCLUSIONS: Our results indicated that the methodological quality of SRs on CHM is low. Future authors should enhance the methodological quality through registering a priori protocols, justifying selection of study designs, conducting comprehensive literature search, providing a list of excluded studies with rationales, using appropriate method for meta-analyses, and reporting funding sources among primary studies.

Chinese herbal medicine for functional dyspepsia: a network meta-analysis of prokinetic-controlled randomised trials.

BACKGROUND: Prokinetic is the first-line conventional treatment for functional dyspepsia (FD) in Asia despite potential adverse events. Chinese herbal medicine (CHM) may be an effective and safe substitution. This network meta-analysis (NMA) aimed to evaluate the comparative effectiveness of different CHM formulae for FD against prokinetics. METHODS: Seven international and Chinese databases were searched from their inception to July 2020 for randomised controlled trials (RCTs) on CHM versus prokinetics. Data from each RCT were first pooled using random-effect pairwise meta-analyses and illustrated as risk difference (RD) or standardised mean difference (SMD) with 95% confidence interval (CI). Random-effect NMAs were then performed to evaluate the comparative effectiveness of CHM formulae and displayed as RD with 95% CI or SMD with 95% credible interval (CrI). The GRADE partially contextualised framework was applied for NMA result interpretation. RESULTS: Twenty-six unique CHM formulae were identified from twenty-eight RCTs of mediocre quality. Pairwise meta-analyses indicated that CHM was superior to prokinetics in alleviating global symptoms at 4-week follow-up (pooled RD: 0.14; 95% CI: 0.10-0.19), even after trim and fill adjustment for publication bias. NMAs demonstrated that Modified Zhi Zhu Decoction may have a moderate beneficial effect on alleviating global symptoms at 4-week follow-up (RD: 0.28; 95% CI: - 0.03 to 0.75). Xiao Pi Kuan Wei Decoction may have a large beneficial effect on alleviating postprandial fullness (SMD: - 2.14; 95% CI: - 2.76 to 0.70), early satiety (SMD: - 3.90; 95% CI: - 0.68 to - 0.42), and epigastric pain (SMD: - 1.23; 95% CI: - 1.66 to - 0.29). No serious adverse events were reported. CONCLUSION: Modified Zhi Zhu Decoction and Xiao Pi Kuan Wei Decoction may be considered as an alternative for patients unresponsive to prokinetics. Confirmatory head-to-head trials should be conducted to investigate their comparative effectiveness against prokinetics.

Low methodological quality of systematic reviews on acupuncture: a cross-sectional study.

BACKGROUND: While well-conducted systematic reviews (SRs) can provide the best evidence on the potential effectiveness of acupuncture, limitations on the methodological rigour of SRs may impact the trustworthiness of their conclusions. This cross-sectional study aimed to evaluate the methodological quality of a representative sample of SRs on acupuncture effectiveness. METHODS: Cochrane Database of Systematic Reviews, MEDLINE, and EMBASE were searched for SRs focusing on the treatment effect of manual acupuncture or electro-acupuncture published during January 2018 and March 2020. Eligible SRs must contain at least one meta-analysis and be published in English language. Two independent reviewers extracted the bibliographical characteristics of the included SRs with a pre-designed questionnaire and appraised the methodological quality of the studies with the validated AMSTAR 2 (A MeaSurement Tool to Assess systematic Reviews 2). The associations between bibliographical characteristics and methodological quality ratings were explored using Kruskal-Wallis rank tests and Spearman's rank correlation coefficients. RESULTS: A total of 106 SRs were appraised. Only one (0.9%) SR was of high overall methodological quality, zero (0%) was of moderate-quality, six (5.7%) and 99 (93.4%) were of low-quality and critically low-quality respectively. Among appraised SRs, only ten (9.4%) provided an a priori protocol, four (3.8%) conducted a comprehensive literature search, five (4.7%) provided a list of excluded studies, and six (5.7%) performed meta-analysis appropriately. Cochrane SRs, updated SRs, and SRs that did not search non-English databases had relatively higher overall quality. CONCLUSIONS: Methodological quality of SRs on acupuncture is unsatisfactory. Future reviewers should improve critical methodological aspects of publishing protocols, performing comprehensive search, providing a list of excluded studies with justifications for exclusion, and conducting appropriate meta-analyses. These recommendations can be implemented via enhancing the technical competency of reviewers in SR methodology through established education approaches as well as quality gatekeeping by journal editors and reviewers. Finally, for evidence users, skills in SR critical appraisal remain to be essential as relevant evidence may not be available in pre-appraised formats.

Prioritizing Chinese medicine clinical research questions in cancer palliative care from patient and caregiver perspectives.

BACKGROUND: Chinese medicine (CM) modalities, including acupuncture and Chinese herbal medicine (CHM), are popular palliative interventions among patients with cancer, but further clinical research is required to assess their effectiveness and safety. OBJECTIVE: To prioritize top ten important CM clinical research questions from patients with cancer, cancer survivors and caregivers' perspectives via a face-to-face prioritization workshop in Hong Kong. METHODS: A list of 25 CM clinical research questions for cancer palliative care, which were identified from existing systematic reviews (SRs) and overview of SRs, was presented to 17 participants (patients with cancer [n = 5], cancer survivors [n = 6] and caregivers [n = 6]). The participants were then invited to establish consensus on prioritizing top ten research questions. RESULTS: Among the top ten priorities, five (50%) focused on acupuncture and related therapies, while five (50%) were on CHM. The three most important research priorities were (i) manual acupuncture plus opioids for relieving pain; (ii) CHM for improving quality of life among patients receiving chemotherapy; and (iii) concurrent use of CHM plus loperamide for reducing stomatitis. CONCLUSION: The top ten participant-endorsed CM clinical research priorities for cancer palliative care can guide local researchers on future direction. They can also inform local research funders on patient-centred allocation of limited funding. Under limited research funding, the most important co-prioritized research question from professional and patient perspectives may be addressed first. PATIENT OR PUBLIC CONTRIBUTION: Patients with cancer, cancer survivors and caregivers participated in conduct of the study to prioritize CM clinical research questions.

Non-Genetic Risk Factors for Parkinson's Disease: An Overview of 46 Systematic Reviews.

BACKGROUND: Numerous systematic reviews (SRs) and meta-analyses on non-genetic risk factors for Parkinson's disease (PD) development have been published with inconsistent conclusions. OBJECTIVE: This overview of SRs aimed to summarize evidence on non-genetic factors for the development of PD from the published SRs, and explore the reasons behind the conflicting results. METHODS: Three international databases were searched for SRs with meta-analyses summarized evidence on non-genetic factors for PD development. The Assessing the Methodological Quality of Systematic Reviews 2 tool was used to appraise the methodological quality of included SRs. Pooled effect estimations were extracted from each meta-analysis. RESULTS: Forty-six SRs covered six categories, and more than 80 factors were included in this overview. Thirty-nine SRs (84.7%) were judged to be of critically low methodological quality. Evidence from prospective studies showed that physical activity, smoking, coffee, caffeine, tea, fat intake, ibuprofen use, calcium channel blocker use, statin use, thiazolidinediones, and high serum urate levels significantly reduced the risk of PD, while dairy intake, diabetes, hormone replacement therapy, depression, mood disorder, bipolar disorder, and aspirin use significantly increased the risk of PD. Differences in study designs (e.g., cohort studies, case-control studies) accounted for the conflicting results among included SRs. CONCLUSION: Modifiable lifestyle factors such as physical activity and tea and coffee drinking may reduce the risk of PD, which may offer PD prevention strategies and hypotheses for future research. However, the designs of primary studies on PD risk factors and related SRs need to be improved and harmonized.

Association Between Vitamin D Exposure and Head and Neck Cancer: A Systematic Review With Meta-Analysis.

Background: Vitamin D deficiency is a well-described preventable cause of many cancers; the association of vitamin D use with the development of head and neck cancer (HNC) is not clear. We aim to conduct a systematic review of the studies assessing the relation between vitamin D exposure and the prevention and prognosis of the HNC using meta-analysis. Methods: PubMed, EMBASE, Cochrane Library, Web of Science up to 1 January 2021, and reference lists of related studies were searched. We extracted observational studies reporting the association between vitamin D (vitamin D receptor gene polymorphisms, 25-hydroxyvitamin D concentrations, and vitamin D intake) and the outcomes of interest (HNC incidence and HNC mortality) in HNC patients aged 18 or older. Fixed effects models were used to calculate pooled effect sizes and 95% confidence intervals (CIs) by RevMan (version 5.3). Results: Sixteen studies with a total of 81,908 participants were enrolled in our meta-analysis. Based on the pooled genomic analysis, comparing with participants with the genotypes of Ff + FF or FF, the pooled odds ratio (OR) of participants with the genotype of ff was 0.77 (95% CI: 0.61 to 0.97) and 0.75 (0.58 to 0.97), respectively. A similar trend was noted when comparing tt with Tt + TT or TT, in which OR (95% CI) was 0.70 (0.55 to 0.90) and 0.72 (0.55 to 0.95). No significant association was identified between BsmI polymorphism and HNC. Furthermore, the OR of HNC incidence was 0.77 (0.65 to 0.92) for participants with vitamin D intake over the ones with a regular diet. High concentrations of circulated 25-hydroxyvitamin D (25-OHD) significantly decreased by 32% of HNC incidence (OR (95% CI): 0.68 (0.59 to 0.78)) and increased HNC survival (pooled hazard ratio 1.13, 1.05 to 1.22) during a 4-5 years follow-up. High concentrations of circulating 25-OHD in patients with HNC led to a decreased risk of mortality to 0.75 (0.60 to 0.94) as the follow-up extends to 8-12 years. Conclusions: Elevated activities of vitamin D by diet intake, genomic polymorphisms, or circulated 25-OHD may protect people from HNC and improve the prognosis of patients with HNC. Systematic Review Registration: PROSPERO, identifier CRD42020176002 (https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=176002).

Chinese medicine diagnosis and treatment for COVID-2019: Is China ready for implementing a national guideline?

OBJECTIVES: COVID-19 sparked a pandemic in December 2019 and is currently posing a huge impact globally. Chinese herbal medicine is incorporated into the Chinese national guideline for COVID-19 management, emphasising the individualisation of herbal treatment guided by pattern differentiation, which is an ICD-11-endorsed approach. However, this was not widely implemented with many provincial governments and hospitals developing their own guideline, suggesting the use of standardised herbal formulae and herbal active ingredients without pattern differentiation. METHODS: Through the case study of COVID-19 guideline implementation, we compared the three approaches of developing Chinese herbal medicine, namely pattern differentiation-guided prescription, standardised herbal formulae, and herbal active ingredients, in terms of their strengths, limitations, and determinants of adoption. RESULTS: Pattern differentiation-guided prescription is the practice style taught in the national syllabus among universities of Traditional Chinese Medicine in China, yet the lack of relevant diagnostic research reduces its reliability and hinders its implementation. Application of standardised herbal formulae is straightforward since the majority of clinical evidence on Chinese herbal medicine is generated using this approach. Nevertheless, it is downplayed by regulatory bodies in certain jurisdictions where the use of pattern differentiation is required in routine practice. Although herbal active ingredients may have clear in vitro therapeutic mechanisms, this may not be translated into real world clinical effectiveness. CONCLUSIONS: Multiple COVID-19 clinical trials evaluating the effectiveness and safety of Chinese herbal medicine prescribed using one of the three approaches described above are progressing. These results will demonstrate the comparative effectiveness among these approaches. Forthcoming clinical evidence from these trials should inform the updating process of the national guideline, such that its recognition and compliance may be strengthened. For longer-term development Chinese herbal medicine, serious investment for establishing high-quality clinical research infrastructure is urgently needed.

Development of Evidence-Based Chinese Medicine Clinical Service Recommendations for Cancer Palliative Care Using Delphi Approach Based on the Evidence to Decision Framework.

Objectives: Existing evidence supports the use of certain Chinese medicine (CM) interventions for symptom management among palliative cancer patients. However, evidence-based service recommendations tailored to the local context are needed for CM planning and implementation. In response, we aimed to establish consensus on CM clinical service recommendations for cancer palliative care among Hong Kong experts. Methods: Seven CM interventions showing statistically significant favorable results in existing systematic reviews (SRs) and overviews of SRs were subjected to a GRADE-ADOLOPMENT-based 2-round Delphi survey. Twelve Hong Kong experts in cancer palliative care, including conventionally trained physicians, CM practitioners, and nurses (n = 4 from each category), were invited to participate. Use of the Evidence to Decision framework within the GRADE-ADOLOPMENT approach enabled experts to consider aspects of problem priority, benefits, harms, equity, acceptability, and feasibility when making CM recommendations in cancer palliative care. Results: Three evidence-based CM interventions reached positive consensus as service recommendations, namely: (1) acupuncture for reducing fatigue among palliative cancer patients; (2) acupressure for reducing fatigue among palliative cancer patients; and (3) moxibustion for reducing nausea and vomiting among patients receiving chemotherapy. Median rating of recommendation ranged from 2.5 to 3.0 (interquartile range = 0.00-1.00) on a 4-point Likert-type scale, and the percentage agreement ranged from 83.4% to 91.7%. Conclusions: The GRADE-ADOLOPMENT approach facilitates a consensus-based process of reaching 3 evidence-based CM recommendations for cancer palliative care. Future studies may develop tailored strategies to implement these recommendations in the Hong Kong health system.

Prioritizing Chinese Medicine Clinical Research Questions in Cancer Palliative Care: International Delphi Survey.

CONTEXT: Chinese medicine modalities, including acupuncture and Chinese herbal medicine (CHM), have been used as palliative interventions among cancer patients. More research should be conducted to confirm their effectiveness. OBJECTIVES: The objective of this study was to prioritize Chinese medicine clinical research questions for cancer palliative care. METHODS: Twelve international experts, including physicians, Chinese medicine practitioners, nurses, and clinical research methodologists (n = 3 from each category), from Asia, North America, Australia, and Europe participated in a two-round Delphi survey for prioritizing 29 research questions identified from existing systematic reviews. The experts were asked to 1) rate clinical importance of answering the questions on a nine-point Likert scale; 2) provide qualitative comments on their ratings; and 3) suggest outcome measurement approaches. RESULTS: Eight research priorities reached positive consensus after the two-round Delphi survey. Six of the priorities focused on acupuncture and related therapies, of which median ratings on importance ranged from 7.0 to 8.0 (interquartile range: 1.00 to 2.50), and the percentage agreement ranged from 75.0% to 91.7%. The remaining two priorities related to CHM, with median ratings ranged from 7.0 to 8.0 (interquartile range: 1.00 to 1.50) and percentage agreement ranged from 75.0% to 83.3%. Neither positive nor negative consensus was established among the remaining 21 questions. CONCLUSION: The findings will inform rational allocation of scarce research funding for evaluating the effectiveness of Chinese medicine for cancer palliative care, especially on acupuncture and related therapies. Further research on herb safety and herb-drug interaction should be performed before conducting international trials on CHM.

Impact of evidence-based healthcare education for Chinese medicine practitioners: A pre-post evaluation.

WHO Traditional Medicine Strategy 2014-23 recommended evidence-based healthcare (EBHC) education for traditional and complementary medicine (T&CM) professionals, including Chinese medicine practitioners (CMPs). We evaluated the impact of a customized educational workshop on Hong Kong CMPs' knowledge, attitude and practice of EBHC. Two validated instruments, Evidence-based Practice Questionnaire (EPQ) and Evidence-based Practice Inventory (EPI), were used to assess the impact of EBHC education. Paired t-tests were used to compare scores before and after the workshop. Multiple linear regression was performed to explore the associations between changes in EPQ/EPI scores and CMPs' characteristics. CMPs who completed the workshop (n = 59) demonstrated significant improvements in the attitude (p = 0.013) and knowledge domains of the EPQ (p = 0.005). Significant improvements were also observed in the attitude, perceived behavioural control, decision making, and intention and behaviour domains of the EPI. CMPs who had never received prior EBHC training showed a larger magnitude of improvement in the EPI attitude (p = 0.032), decision making (p = 0.015), and intention and behaviour (p = 0.015) domains post-workshop. Our findings suggest that tailored workshop is effective in strengthening knowledge and in improving attitudes towards EBHC. Future RCTs should be conducted to affirm our findings. Future initiatives may consider incorporating this education approach into CMP curricula, as well as facilitating implementation of EBHC in routine Chinese medicine practice.

Acupuncture and related therapies for treating irritable bowel syndrome: overview of systematic reviews and network meta-analysis.

BACKGROUND: An overview of systematic reviews (SRs) and a network meta-analysis (NMA) were conducted to evaluate the comparative effectiveness of acupuncture and related therapies used either alone, or as an add-on to other irritable bowel syndrome (IBS) treatments. METHODS: A total of eight international and Chinese databases were searched for SRs of randomized controlled trials (RCTs). The methodological quality of SRs was appraised using the AMSTAR instrument. From the included SRs, data from RCTs were extracted for the random-effect pairwise meta-analyses. An NMA was used to evaluate the comparative effectiveness of different treatment options. The risk of bias among included RCTs was assessed using the Cochrane risk of bias tool. RESULTS: From 15 SRs of mediocre quality, 27 eligible RCTs (n = 2141) were included but none performed proper blinding. Results from pairwise meta-analysis showed that both needle acupuncture and electroacupuncture were superior in improving global IBS symptoms when compared with pinaverium bromide. NMA results showed needle acupuncture plus Geshanxiaoyao formula had the highest probability of being the best option for improving global IBS symptoms among 14 included treatment options, but a slight inconsistency exists. CONCLUSION: The risk of bias and NMA inconsistency among included trials limited the trustworthiness of the conclusion. Patients who did not respond well to first-line conventional therapies or antidepressants may consider acupuncture as an alternative. Future trials should investigate the potential of (1) acupuncture as an add-on to antidepressants and (2) the combined effect of Chinese herbs and acupuncture, which is the norm of routine Chinese medicine practice.

Chinese herbal medicine for functional dyspepsia: systematic review of systematic reviews.

BACKGROUND: Pharmacotherapy, including prokinetics and proton pump inhibitors for functional dyspepsia (FD) have limited effectiveness, and their safety has been recently questioned. Chinese herbal medicine (CHM) could be considered as an alternative. A systematic review (SR) of SRs was performed to evaluate the potential effectiveness and safety of CHM. METHOD: We conducted a comprehensive literature search for SRs with meta-analyses in eight international and Chinese databases. Pooled effect estimation from each meta-analysis was extracted. The AMSTAR instrument was used to assess the methodological quality of the included SRs. RESULTS: A total of 14 SRs of mediocre quality assessing various CHMs, alone or in combination with conventional pharmacotherapy, were included. Meta-analyses showed that CHM was more effective than prokinetic agents for the alleviation of global dyspeptic symptoms. Three specific CHM formulae appeared to show superior results in the alleviation of global dyspeptic symptoms, including Si Ni San, modified Xiao Yao San and Xiang Sha Liu Jun Zi decoction. No significant difference in the occurrence of adverse events in using CHM or pharmacotherapy was reported. CONCLUSION: CHM can be considered as an alternative for the treatment of FD symptoms when prokinetic agents and proton pump inhibitors are contraindicated. Future trial design should focus on measuring changes in individual dyspeptic symptoms and differentiate the effectiveness of different CHM for postprandial distress syndrome and epigastric pain syndrome. A network meta-analysis approach should be used to explore the most promising CHM formula for FD treatment in the future.

Acupuncture and related therapies used as add-on or alternative to prokinetics for functional dyspepsia: overview of systematic reviews and network meta-analysis.

Prokinetics for functional dyspepsia (FD) have relatively higher number needed to treat values. Acupuncture and related therapies could be used as add-on or alternative. An overview of systematic reviews (SRs) and network meta-analyses (NMA) were performed to evaluate the comparative effectiveness of different acupuncture and related therapies. We conducted a comprehensive literature search for SRs of randomized controlled trials (RCTs) in eight international and Chinese databases. Data from eligible RCTs were extracted for random effect pairwise meta-analyses. NMA was used to explore the most effective treatment among acupuncture and related therapies used alone or as add-on to prokinetics, compared to prokinetics alone. From five SRs, 22 RCTs assessing various acupuncture and related therapies were included. No serious adverse events were reported. Two pairwise meta-analyses showed manual acupuncture has marginally stronger effect in alleviating global FD symptoms, compared to domperidone or itopride. Results from NMA showed combination of manual acupuncture and clebopride has the highest probability in alleviating patient reported global FD symptom. Combination of manual acupuncture and clebopride has the highest probability of being the most effective treatment for FD symptoms. Patients who are contraindicated for prokinetics may use manual acupuncture or moxibustion as alternative. Future confirmatory comparative effectiveness trials should compare clebopride add-on manual acupuncture with domperidone add-on manual acupuncture and moxibustion.