Efficacy and Safety of Traditional Chinese Medicine Injections for Heart Failure With Reduced Ejection Fraction: A Bayesian Network Meta-Analysis of Randomized Controlled Trials.

Background: Heart failure as an important issue in global public health, has brought a heavy economic burden. Traditional Chinese medicine injections (TCMIs) have significant effects on heart failure with reduced ejection fraction (HFrEF). However, it is difficult for clinicians to identify the differences in clinical efficacy and safety of various TCMIs. The purpose of this study is to compare the efficacy and safety of various TCMIs for treating HFrEF by conducting a Bayesian network meta-analysis (NMA) and to further provide references for clinical decision-making. Methods: The clinical randomized controlled trials of TCMIs for treating HFrEF were searched in seven database from inception to August 3rd, 2021. The Cochrane collaboration's tool was used to assess the risk of bias. NMA was performed in a Bayesian hierarchical framework. The surface under the cumulative ranking curve (SUCRA), the multi-dimensional efficacy analysis, the comparison-adjusted funnel plot, and the node-splitting analysis were conducted using R software. Results: A total of 107 eligible RCTs involving 9,073 HFrEF patients and 6 TCMIs were included. TCMIs include Huangqi injection (HQ) also called Astragalus injection, Shenfu injection (SF), Shengmai injection (SGM), Shenmai injection (SM), Xinmailong injection (XML), and Yiqifumai lyophilized injection (YQFM). The results of NMA and SUCRA showed that with conventional treatment (CT) as a common control, in terms of clinical efficacy, CT + XML was most effective in New York Heart Association cardiac functional classification efficiency, brain natriuretic peptide, and N-terminal pro-brain natriuretic peptide; the CT + SM was most effective in 6-min walking test, left ventricular end-diastolic diameter, left ventricular end-systolic diameter and cardiac output; the CT + YQFM was most effective in left ventricular ejection fraction; the CT + HQ was most effective in stroke volume; the CT + SF was most effective in Minnesota Living with Heart Failure Questionnaire. In terms of safety, there was no significant difference between CT + TCMIs and CT. Conclusion: This Bayesian network meta-analysis results show that the combination of qualified TCMIs and CT is more effective for HFrEF patients than CT alone, and CT + XML and CT + SM may be one of the potential optimal treatments. Also, the safety of these TCMIs needs to be further observed. However, due to some limitations, the conclusions need to be verified by more large-sample, double-blind, multi-center RCTs.

The Preventive Value of Acupoint Sensitization for Patients with Stable Angina Pectoris: A Randomized, Double-Blind, Positive-Controlled, Multicentre Trial.

BACKGROUND: Acupoint sensitization is considered an important factor in the efficacy of acupoint therapy. This study aimed to evaluate the efficacy of acupressure in the prevention of stable angina pectoris using acupoints with different pressure-pain sensitivities. METHODS: A total of 202 patients were enrolled and randomly assigned to a high-sensitivity group (HSG) (n = 109) in which patients received acupressure at the five acupoints with the highest sensitivity to pain and a low-sensitivity group (LSG) (n = 93) in which patients received acupressure at the five acupoints with the lowest sensitivity to pain. The duration of acupressure treatment was 4 weeks, and the patients were evaluated at baseline, week 4, and week 8. The primary outcome was a change in the frequency of angina attacks from baseline. The secondary outcomes included nitroglycerin consumption, the Canadian Cardiovascular Society classification, and the Seattle Angina Questionnaire score. Adverse events such as bleeding and subcutaneous haemorrhage were recorded in both groups. RESULTS: The effect of acupressure compared with baseline on the prevention of angina pectoris in HSG was better than that in LSG at week 4 (incidence rate ratio (IRR): 0.691 and 95% confidence interval (CI): [0.569, 0.839]) and week 8 (IRR: 0.692 and 95% CI: [0.569, 0.839]). No significant difference between groups was found in the frequency of nitroglycerin consumption at week 4 (odds ratio (OR) = 0.863 and 95% CI: [0.147, 5.077]) or week 8 (OR = 1.426 and 95% CI: [0.211, 9.661]). Two themes in the questionnaire showed significantly different changes from baseline between the two groups. Scores on the angina frequency (AF) subscale had changed more from the baseline in the HSG at week 8 than in the LSG (mean difference (MD) = 3.807 and 95% CI: [0.673, 6.942]). Scores on the treatment satisfaction (TS) subscale had also changed more in the HSG than in the LSG at week 4 (MD = 3.651 and 95% CI: [0.327, 7.327]) and week 8 (MD = 4.220 and 95% CI: [0.347, 7.346]). One patient in the LSG reported bruising at the acupoint. No unexpected safety problems arose. CONCLUSIONS: This study showed that acupressure at acupoints with high sensitivity to pain may effectively reduce the frequency of stable angina pectoris episodes. This trial is registered with NCT03975140.

Traditional Chinese Medicine Oral Liquids Combined With Azithromycin for Mycoplasma pneumoniae Pneumonia in Children: A Bayesian Network Meta-Analysis.

Background: Mycoplasma pneumoniae pneumonia (MPP) causes flu-like symptoms in children, increasing the burden on the health and education systems. In China, traditional Chinese medicine oral liquids (TCMOLs) combined with azithromycin (TCMOLs + Azithromycin) is commonly used to treat MPP in children. However, TCMOLs with the optimal clinical applicability remain unknown. Here, we evaluated the clinical effectiveness and safety of TCMOLs + Azithromycin in children with MPP. Methods: We searched PubMed, Embase, Cochrane Library, Ovid, Web of Science, China National Knowledge Infrastructure (CNKI), Wanfang Data Knowledge Service Platform, and VIP information resource integration service platform databases for eligible randomized controlled trials (RCTs) published from database inception to October 2020. Two reviewers independently performed data extraction and risk of bias assessment. After Bayesian random effect modeling and surface under the cumulative ranking curve (SUCRA) scoring, we ranked each intervention. We assessed heterogeneity using multivariate meta-regression for potential modifiers and used the Grading of Recommendations, Assessment, Development, and Evaluation to rate pooled evidence's certainty. Results: In the 63 included RCTs with 6,410 children, five different TCMOLs were combined with azithromycin. TCMOLs + Azithromycin had significantly better primary outcomes than did azithromycin alone. Of all TCMOLs, Xiaoer Xiaoji Zhike (XEXJZK)+Azithromycin showed the best effectiveness with respect to the response rate (odds ratio [OR] = 6.5, 95% credible interval [CrI] = 4.3-10; low certainty) and pulmonary rales disappearance time (mean difference [MD] = -2.1, 95% CrI: -2.9 to -1.2; low certainty) with SUCRA 85 and 80%, respectively. Pudilan Xiaoyan + Azithromycin showed the highest effectiveness with respect to cough disappearance time (MD = -2.6, 95% CrI: -3.4 to -1.7; very low certainty) and fever disappearance time (MD = -1.8, 95% CrI: -2.3 to -1.3; very low certainty) with SUCRA 87 and 87%, respectively. The difference in the adverse effects between TCMOLs + Azithromycin and azithromycin alone was nonsignificant. Conclusion: Of the different TCMOLs, XEXJZK may be the best option to combine with azithromycin to treat children with MPP. However, our results should be interpreted with caution due to the low certainty of evidence. In general, TCMOLs' safety remains unclear because of a lack of evidence. More high-quality RCTs are needed to further evaluate efficacy and safety of these TCMOLs.

Comparative Efficacy of Pharmacological and Nonpharmacological Interventions for Acne Vulgaris: A Network Meta-Analysis.

Acne has several effects on physical symptoms, but the main impacts are on the quality of life, which can be improved by treatment. There are several acne treatments but less evidence comparing their relative efficacy. Thus, we assessed the comparative efficacy of pharmacological and nonpharmacological interventions for acne. We searched PubMed, Embase, and the Cochrane Central Register of Controlled Trials from inception to April 2019, to include randomized controlled trials for acne that compared topical antibiotics (TA), benzoyl peroxide (BPO), topical retinoids (TR), oral antibiotics (OA), lasers, light devices including LED device (LED), photodynamic therapy (PDT), and intense pulsed light, chemical peels (CP), miscellaneous therapies or complementary and alternative medicine (MTCAM), or their combinations. We performed Bayesian network meta-analysis with random effects for all treatments compared with placebo and each other. Mean differences (MDs) of lesions count and risk ratios of adverse events with their 95% credible intervals (CrIs) were calculated, and all interventions were ranked by the Surface Under the Cumulative Ranking (SUCRA) values. Additional frequentist additive network meta-analysis was performed to detect the robustness of results and potential interaction effects. Sensitivity analyses were carried out with different priors, and metaregression was to adjust for nine potential effect modifiers. In the result, seventy-three randomized controlled trials (27,745 patients with mild to moderate acne), comparing 30 grouped intervention categories, were included with low to moderate risk of bias. For adverse effects, OA had more risk in combination treatment with others. For noninflammatory lesions reduction, seventeen interventions had significant differences comparing with placebo and three interventions (TR+BPO: MD = -21.89, 95%CrI [-28.97, -14.76]; TR+BPO+MTCAM: -22.48 [-34.13, -10.70]; TA+BPO+CP: -20.63 [-33.97, -7.13]) were superior to others with 94, 94, and 91% SUCRA values, respectively. For inflammatory lesions reduction, nineteen interventions were significantly better than placebo, and three interventions (TR+BPO: MD = -12.13, 95%CrI [-18.41, -5.80]; TR+BPO+MTCAM: -13.21 [-.39, -3.04]; LED: -11.30 [-18.34, -4.42]) were superior to others (SUCRA: 81, 81, and 77%, respectively). In summary of noninflammatory and inflammatory lesions results, TR+BPO and TA+BPO were the best options compared to others. The frequentist model showed similar results as above. In summary, current evidence supports the suggestion that TR+BPO and TA+BPO are the best options for mild to moderate acne. LED is another option for inflammatory lesions when drug resistance occurs. All the combinations involved with OA showed more risk of adverse events than others. However, the evidence of this study should be cautiously used due to the limitations.

Traditional Chinese medicine injections for heart failure: a protocol for systematic review and network meta-analysis of randomised controlled trials.

INTRODUCTION: Heart failure (HF) has always been an important issue in global public health. The research and development of traditional Chinese medicine (TCM) provide more possibilities for improving the prognosis of HF patients. Because multiple TCM injections (TCMIs) are being widely applied in clinical work, it is important to choose the right TCMIs for HF patients. The purpose of this study is to assess and compare the effect of different TCMIs for HF using network meta-analysis (NMA) and further provide references for clinical decision-making. METHODS AND ANALYSIS: The clinical randomised controlled trials (RCTs) and meta-analyses of TCMIs for treating HF will be searched in the relevant database, including PubMed, EMBASE, Cochrane Library (No. 2 of 2020), Chinese BioMedical Literature Database, China National Knowledge Infrastructure, Wan Fang Database and Chinese Scientific Journal Database from inception to 29 February 2020. The outcomes of interest include all-cause mortality, rehospitalisation rate, left ventricular ejection fraction, left ventricular end-diastolic diameter, left ventricular end-systolic diameter, brain natriuretic peptide (BNP), N-terminal pro-BNP, cardiac output, stroke volume, 6 min walking distance and adverse events. The risk of bias assessment of the included RCTs will be conducted according to the Cochrane Collaboration's tool for assessing the risk of bias. NMA will be performed in a Bayesian hierarchical framework using R V.3.6.1 with the gemtc package. Finally, we will rank the efficacy of these treatment programmes according to the surface under the cumulative ranking curve, and perform quality assessment and recommendation grading of the evidence according to the Grading of Recommendations Assessment, Development and Evaluation system. ETHICS AND DISSEMINATION: This study will extract data from the published literature and will not involve private information from individuals or compromise their rights. Therefore, the study does not require ethical approval. The results will eventually be published in a peer-reviewed journal and disseminated at relevant conferences. PROSPERO REGISTRATION NUMBER: CRD42020166900.

Traditional Chinese Patent Medicine for Primary Hypertension: A Bayesian Network Meta-Analysis.

BACKGROUND: Traditional Chinese Patent Medicine (TCPM) is now being used more and more extensively for primary hypertension in China. However, the comparative efficacy and safety of it need more clarified evidence. Thus, we conducted a Bayesian network meta-analysis to compare TCPMs with other interventions. METHODS: We searched China National Knowledge Infrastructure (CNKI), WanFang Data, PubMed, Embase, and Cochrane Library from inception to April 2019 for randomized controlled trials (RCTs) with diagnosis of primary hypertension that compared the efficacy of TCPMs with antihypertension drugs (ADs). Two researchers screened literature, extracted data, and evaluated risk of bias independently. The primary outcomes were systolic blood pressure (SBP) and diastolic blood pressure (DBP). The secondary outcomes were adverse effects (AEs), total cholesterol (TC), and triglyceride (TG). We used the Bayesian network meta-analysis to compare interventions and described the categorical variable and the continuous variable as odds ratio (OR) and mean difference (MD), respectively. Besides, we ranked all interventions via the Surface Under the Cumulative Ranking (SUCRA) values and conducted metaregression with nine covariates as additional analysis. RESULTS: We included 192 studies with 23366 patients diagnosed as primary hypertension in total. For SBP reduction, eighteen interventions were significantly better than AD. Among them, Yinxingye (YXY) + AD (MD = -12, 95% CrI [-16, -8.5]) was superior to others in the rank plot with SUCRA 0.91. For DBP reduction, sixteen interventions were significantly better than AD. Among them, Qinggan Jiangya (QGJY) + AD (MD = -8.7, 95% CrI [-12, -5.5]) and Qiju Dihuang (QJDH) + AD (MD = -8.8, 95% CrI [-12, -5.2]) were superior to others in the rank plot with SUCRA 0.89. To summarize the SUCRA values, we found that QGJY + AD and YXY + AD had the most significant reductions for both SBP and DBP. YXY + AD was the best one for both TC (MD = -1.3, 95% CrI [-1.9, -0.64]) and TG (MD = -0.52, 95% CrI [-0.92, -0.11]) reductions. Considering adverse effects, we found two interventions had significant differences comparing with AD. Among them, YXY + AD was the best one with SUCRA of 0.01. CONCLUSION: In all TCPMs, QGJY + AD and YXY + AD may be the best options for hypertension. Meanwhile, YXY + AD can improve blood lipids in patients with hypertension. However, due to the vague reports of adverse effects and other limitations, more evidence, especially that provided by high-quality studies, is needed to prove the advantages of TCMPs.

Comparative efficacy of pharmacological and nonpharmacological treatments for chronic idiopathic constipation in China: a Bayesian network meta-analysis.

BACKGROUND: To provide evidence for medical management of chronic idiopathic constipation (CIC) in China based on comparisons of all clinical practical interventions using Bayesian network meta-analysis. METHODS: We conducted a systematic literature review by searching PubMed, Embase, Cochrane Central, the China National Knowledge Infrastructure (CNKI), and the Wanfang Database (inception to May 2019) for randomized controlled trials (RCTs) for CIC in Chinese people. Only RCTs that recruited participants aged over 18 and diagnosed with CIC by the Rome II, III or IV criteria were included. We used three outcomes to examine efficacy. The risk ratio (RR) of the responder rate, based on ≥3 spontaneous bowel movements (SBMs) per week after treatment, was the primary outcome, and the SBM count per week and the Bristol score (BS) were secondary outcomes. In addition, adverse effects (AEs) were also considered a secondary outcome to evaluate safety. We conducted Bayesian network meta-analysis with random effects, and the RR or mean difference with its 95% credible interval was calculated. In addition, we ranked all treatments via their cumulative curves (SUCRA) and assessed the quality of evidence according to the GRADE criteria. RESULTS: We included a total of 42 trials (6820 participants) of 20 grouped interventions that included pharmacological and nonpharmacological treatments. For the primary outcome, fourteen interventions were significantly better than placebo, and Probiotics plus Mosapride (PB + MP) appeared superior to others (GRADE quality of evidence: Moderate to Low), followed by Prucalopride (PP) (High to Low) and Electroacupuncture (EA) (High to Low). For SBM, Compound sodium bicarbonate suppository (CSBS) appeared to be best, with an SUCRA value of 90% (High to Low). For BS, Lactulose plus Probiotics (LT + PB) was superior to others (Moderate to Low), followed by Polyethylene glycol (PEG) (High to Moderate). Although all interventions appeared non-significant when compared with placebo in terms of adverse effects, Lactulose plus Mosapride showed greater risk than others on ranking probability. CONCLUSIONS: Given the GRADE assessment, PB + MP, PP and EA may be the priory options with moderate certainty in the quality of evidence for the primary outcome. For SBM, a CSBS may be the best option with moderate certainty in the quality of evidence. For BS, PEG may be the priory option with high certainty in the quality of evidence. However, due to a lack of high certainty in the quality of evidence, caution is needed when recommending the interventions. Because of the limitations, an increased number of trials are required for more accurate results.

Traditional Chinese Medicine Injections in the Treatment of Diabetic Foot: A Systematic Review and Meta-Analysis.

CONTEXT: The role of traditional Chinese medicine injections (TCMIs) in diabetic foot (DF) has not been well estimated. OBJECTIVE: To evaluate the clinical effective rate, safety, and the financial cost of TCMIs in treating DF and ulcer wound healing. METHODS: We searched PubMed, Embase, CENTRAL, China National Knowledge Infrastructure (CNKI), VIP database, and Wanfang database from inception to May 2018 to find all randomized control trials (RCTs) related to TCMIs in DF treatment. The search items were "Traditional Chinese Medicine Injection" AND "Diabetic foot or Diabetic foot ulcer" AND "random". STUDY SELECTION AND SYNTHESIS: Only RCTs of TCMIs combined conventional therapies versus conventional therapies and that can be quantitatively synthesized were included. Finally, 17 studies and 1294 participants were included after extraction. Two investigators independently extracted and analyzed the data using RevMan5.3 software. RESULTS: The overall clinical effective rate of TCMI groups is higher than that of control groups [RR=1.27, 95CI % (1.20, 1.34), P<0.00001] based on fixed effect model analysis. Regarding motor nerve conduction velocity of median nerve and peroneal nerve, TCMI group showed a significant improvement (MD=3.84[2.28, 5.41], P<0.00001; MD=2.89[0.63, 5.15], P=0.01). Regarding plasma viscosity TCMI group showed a statistically difference (MD=0.27[0.04, 0.49], P=0.02). In terms of blood viscosity at high shear rate, there was an improvement of TCMI group (MD=0.36[0.05, 0.67], P=0.02). However, sensory nerve conduction velocity of peroneal nerve and median nerve showed a contradiction to motor nerve conduction velocity, respectively (MD=2.59[-1.69, 6.87], p=0.24; MD=2.73[-0.96, 6.43], P=0.15). CONCLUSION: The data of this study shows that TCMIs can bring benefits to patients with diabetic foot. However, due to low methodological quality of included RCTs, more rigorous designed RCTs with large sample size are recommended to provide more high-quality evidence.