Background: Diarrhea is a ubiquitous digestive system disease, leading to loss of fluid and electrolytes, and may be life-threatening, especially in children and adults who are immunosuppressed or malnourished. Berberine has a broad-spectrum antibiotic activity and is very widely used to treat diarrhea in China. No systematic review has been carried out to evaluate the evidence presented in clinical trials. The aim of this study was to assess the effectiveness and safety of berberine in diarrhea treatment among children and adults. Methods: Seven databases and two clinical trial registries were searched on 1 September 2019. Randomized controlled trials were included, where participants were diagnosed (first diagnosed) as having diarrhea according to clear diagnostic criteria. Berberine alone or in combination with Western medication as intervention were included. Subgroup analyses were conducted based on children or adults, acute or persistent diarrhea, infectious or noninfectious and treatment courses. Primary outcomes were clinical cure rate and duration of diarrhea. The GRADE tool was used to assess the quality of evidence. Results: A total of 38 randomized controlled trials were included involving 3948 participants (including 27 trials on 2702 children) were included. Compared with antibiotics, berberine plus antibiotics showed better results in both adults and in children in general, especially when given for 7 days or 3 days in acute infectious diarrhea of children. Compared with the control groups, using berberine alone or in combination with montmorillonite, probiotics, and vitamin B increased the clinical cure rate of diarrhea. The use of berberine alone or berberine combined with montmorillonite reduced the duration of hospitalization. Using berberine had significantly better laboratory indicators (isoenzyme, inflammatory factors, myocardial enzyme, and fecal trait) and fewer systemic symptoms than the no berberine groups. Overall, 22 of 27 trials on children used berberine as an enema. No deaths and serious adverse events were reported. The quality of evidence of included trials was moderate to low or very low. The impact of different dosages, frequencies and treatment durations on the outcomes was not evaluated due to insufficient number of trials. Conclusion: This review demonstrated that berberine was generally effective in improving clinical cure rates and shortening the duration of diarrhea compared with control groups. No severe adverse event was reported. However, there is still a lack of high-quality evidence for evaluating the efficacy and safety of berberine. Trial registration: PROSPERO CRD42020151001 (available from http://www.crd.york.ac.uk/PROSPERO/ ).

Background: This is the second part of a large spectrum systematic review which aims to identify and assess the evidence for the efficacy of non-pharmacological acupuncture techniques in the treatment of chronic obstructive pulmonary disease (COPD). The results of all techniques except for filiform needle are described in this publication. Methods: Eleven different databases were screened for randomised controlled trials up to June 2019. Authors in pairs extracted the data and assessed the risk of bias independently. RevMan 5.3 software was used for the meta-analysis. Results: Thirty-three trials met the inclusion criteria, which involved the follow techniques: AcuTENS (7 trials), moxibustion (11 trials), acupressure (7 trials), ear acupuncture (6 trials), acupressure and ear acupuncture combined (1 trial) and cupping (1 trial). Due to the great heterogeneity, only 7 meta-analysis could be performed (AcuTENS vs sham on quality of life and exercise capacity, acupressure vs no acupressure on quality of life and anxiety and ear acupuncture vs sham on FEV₁ and FEV₁/FVC) with only acupressure showing statistical differences for quality of life (SMD: -0.63 95%CI: − 0.88, − 0.39 I² = 0%) and anxiety (HAM-A scale MD:-4.83 95%CI: − 5.71, − 3.94 I² = 0%). Conclusions: Overall, strong evidence in favour of any technique was not found. Acupressure could be beneficial for dyspnoea, quality of life and anxiety, but this is based on low quality trials. Further large well-designed randomised control trials are needed to elucidate the possible role of acupuncture techniques in the treatment of COPD. Trial registration: PROSPERO (identifier: CRD42014015074).

As clinical trials evaluating the efficacy of traditional Chinese medicine (TCM) therapies have increased, several empirical studies have shown that the quality of TCM trials is generally low in terms of risk of bias. This qualitative study aimed to investigate the factors influencing the quality of TCM clinical trials to provide strategic advice on trial quality improvement. One focus group with clinical trial auditors (n = 4) and six in-depth semi-structured interviews with clinical research organization managers (n = 2), lecturers and researchers in TCM academic institutions (n = 2), a chief physician in a TCM oncology department and a PhD candidate specialized in non-pharmaceutical TCM interventions were conducted. The interviews were audio-recorded, transcribed verbatim and thematically analyzed. Factors that influenced the quality of TCM clinical trials emerged with the following 6 themes: trial design; trialists/participants; trial conducting; TCM specified problems; trial monitoring, and finally societal influences. The lack of expertise and time inputs of the trialists were repeatedly mentioned. Methodological difficulties experienced when conducting TCM trials including calculating sample size, analyzing the efficacy of TCM decoctions with multiple ingredients, blinding in trials investigating non-pharmaceutical TCM interventions were highlighted. Interviewees agreed that third-party monitoring can help improving trial quality and improve participant welfare, may accelerate recruiting processes and increase compliance; however more comprehensive regulations and funding requirements would be needed. This study identified real-life issues influencing the quality of TCM clinical trials from design to reporting. In addition to mandatory training for TCM trial designers and coordinators, more effective institutional oversight is required. Future studies should explore specific measures to address the methodological problems in TCM trials and explore how the quality of TCM trials can affect further evidence synthesis and clinical practice.

Objectives This is a protocol for a Cochrane Review (intervention). The objectives are as follows: To investigate whether acupuncture is more effective than 'sham' (placebo) acupuncture, no preventative treatment or routine care only, or other interventions, in reducing headache frequency in people with episodic migraine.