Inibidores BTK e BCL-2 no Tratamento de Primeira Linha da Leucemia Linfocítica Crônica em Pacientes de Alto Risco: Revisão Sistemática e Meta-Análise em Rede / BTK and BCL-2 Inhibitors in the First-Line Treatment of Chronic Lymphocytic Leukemia in High-Risk Patients: Systematic Review and Network Meta-Analysis / Inhibidores de BTK Y BCL-2 en el Tratamiento de Primera Línea de la Leucemia Linfocítica Crónica en Pacientes de Alto Riesgo: Revisión Sistemática y un Metaanálisis en Red

Introdução: Pacientes com leucemia linfocítica crônica (LLC) com alto risco têm menores taxas de resposta, curso clínico mais agressivo e resistência à quimioterapia padrão, representando um desafio para o tratamento. Os inibidores da tirosina quinase de Bruton (BTK ­ ibrutinibe e acalabrutinibe) e o inibidor BCL-2 (venetoclax) podem ser utilizados nesses casos. Objetivo: Identificar e avaliar a eficácia e a segurança do uso de ibrutinibe, acalabrutinibe e venetoclax no tratamento de primeira linha em pacientes com LLC de alto risco. Método: Revisão sistemática de ensaios clínicos randomizados que avaliaram pacientes adultos com LLC, portadores de deleção 17p ou mutação TP53 e sem tratamento prévio. Foram pesquisadas as bases PubMed, EMBASE, LILACS e Cochrane Library, e realizadas avaliação do risco de viés pela ferramenta RoB 2 da Cochrane e avaliação da qualidade da evidência pelo GRADE. Resultados: Na meta-análise em rede para sobrevida livre de progressão (SLP), venetoclax + obinutuzumabe (RR: 0,62; IC 95% 0,41-0,95; p = 0,027) e acalabrutinibe + obinutuzumabe (RR: 0,74; IC 95% 0,55-0,99; p = 0,043) apresentaram menor risco de progressão ou óbito, com significância considerada limítrofe. Ibrutinibe + obinutuzumabe (RR: 0,93; IC 95% 0,86-1,00; p = 0,054) não apresentou diferença significativa na SLP para pacientes com LLC de alto risco. Conclusão: O tratamento de primeira linha com inibidores de BTK (ibrutinibe e acalabrutinibe) e o inibidor BCL-2 (venetoclax), associados a agentes monoclonais anti-CD20 ­ especialmente o obinutuzumabe ­, tem sido proposto como padrão para a maioria dos pacientes com LLC. Entretanto, pelos resultados desta revisão com meta-análise em rede, não foi possível confirmar essa recomendação.

Introduction: Patients with high-risk chronic lymphocytic leukemia (CLL) have lower response rates, a more aggressive clinical course, and resistance to standard chemotherapy, representing a treatment challenge. Bruton's tyrosine kinase inhibitors (BTK ­ ibrutinib and acalabrutinib) and the BCL-2 inhibitor (venetoclax) can be used in these cases. Objective: To identify and evaluate studies on the efficacy and safety of the use of ibrutinib, acalabrutinib and venetoclax in first-line treatment in patients with high-risk CLL. Method:Systematic review of randomized clinical trials that evaluated adult patients with CLL, carriers of 17p deletion or TP53 mutation and without prior treatment. The PubMed, EMBASE, LILACS and Cochrane Library databases were searched, and the risk of bias was assessed using the Cochrane RoB 2 tool and the quality of evidence was assessed with GRADE. Results: In the network meta-analysis for progression-free survival (PFS) venetoclax + obinutuzumab (RR: 0.62; 95%CI 0.41-0.95; p value 0.027) and acalabrutinib + obinutuzumab (RR: 0. 74; 95% CI 0.55-0.99; p value 0.043) presented a lower risk of progression or death, with significance considered borderline. Ibrutinib + obinutuzumab (RR: 0.93; 95% CI 0.86-1.00; p value 0.054) did not show a significant difference in PFS for patients with high-risk CLL. Conclusion: First-line treatment with BTK inhibitors (ibrutinib and acalabrutinib) and the BCL-2 inhibitor (venetoclax) associated with anti-CD20 monoclonal agents ­ especially obinutuzumab ­ have been proposed as the standard for most patients with CLL. However, based on the results of this review with network meta-analysis, it was not possible to confirm this recommendation.

Introducción: Los pacientes con leucemia linfocítica crónica (LLC) de alto riesgo tienen tasas de respuesta más bajas, un curso clínico más agresivo y resistencia a la quimioterapia estándar, lo que representa un desafío para el tratamiento. En estos casos se pueden utilizar los inhibidores de la tirosina quinasa de Bruton (BTK - ibrutinib y acalabrutinib) y el inhibidor de BCL-2 (venetoclax). Objetivo:Identificar y evaluar estudios sobre la eficacia y seguridad del uso de ibrutinib, acalabrutinib y venetoclax en el tratamiento de primera línea en pacientes con LLC de alto riesgo. Método: Revisión sistemática de ensayos clínicos aleatorios que evaluaron pacientes adultos con LLC, portadores de deleción 17p o mutación TP53 y sin tratamiento previo. Se realizaron búsquedas en las bases de datos PubMed, EMBASE, LILACS y Cochrane Library y se evaluó el riesgo de sesgo mediante la herramienta Cochrane RoB 2 y la calidad de la evidencia se evaluó mediante GRADE. Resultados: En el metaanálisis en red para la supervivencia libre de progresión (SSP) venetoclax + obinutuzumab (RR: 0,62; IC 95% 0,41-0,95; valor de p 0,027) y acalabrutinib + obinutuzumab (RR: 0,74; IC 95%). 0,55-0,99; valor de p 0,043) presentaron un menor riesgo de progresión o muerte, con una significación considerada límite. Ibrutinib + obinutuzumab (RR: 0,93; IC del 95 %: 0,86-1,00; valor de p 0,054) no mostró una diferencia significativa en la SSP para pacientes con LLC de alto riesgo. Conclusión: El tratamiento de primera línea con inhibidores de BTK (ibrutinib y acalabrutinib) y el inhibidor de BCL-2 (venetoclax), asociados con agentes monoclonales anti-CD20, especialmente obinutuzumab, se ha propuesto como estándar para la mayoría de los pacientes con LLC. Sin embargo, según los resultados de esta revisión con metaanálisis en red, no fue posible confirmar esta recomendación

Comparative efficacy and safety of anti-infective drugs for patients with mild to severe COVID-19: A systematic review and network meta-analysis of randomized controlled trials

Different anti-infecthe drugs have been proposedfor the treatment ofpatients with COVID-19. We carried out a network meta-analysis to assess their relath'e efficacy and safety. Methods: We searched relevant databases for all randomized controlled trials that reported the efficacy and or safety ofany anti-infective drugs published up to April 30, 2022 for different outcomes. We did both painvise and network meta-analysis with 95% confidence intervals using afixed-effect model. We assessed studies for quality of evidence using an extension of the standard Grading ofRecommendations, Assessment, Development and Evaluation approach considering P

Chemoprevention of colorectal cancer in general population and high-risk population: a systematic review and network meta-analysis / 中华医学杂志(英文版)

BACKGROUND@#Many nutritional supplements and pharmacological agents have been reported to show preventive effects on colorectal adenoma and colorectal cancer (CRC). We performed a network meta-analysis to summarize such evidence and assess the efficacy and safety of these agents.@*METHODS@#We searched PubMed, Embase, and the Cochrane Library for studies published in English until October 31, 2021 that fit our inclusion criteria. We performed a systematic review and network meta-analysis to assess the comparative efficacy and safety of candidate agents (low-dose aspirin [Asp], high-dose Asp, cyclooxygenase-2 inhibitors [coxibs], calcium, vitamin D, folic acid, ursodeoxycholic acid [UDCA], estrogen, and progesterone, alone or in combination) for preventing colorectal adenoma and CRC. Cochrane risk-of-bias assessment tool was employed to evaluate the quality of each included study.@*RESULTS@#Thirty-two randomized controlled trials (278,694 participants) comparing 13 different interventions were included. Coxibs significantly reduced the risk of colorectal adenoma (risk ratio [RR]: 0.59, 95% confidence interval [CI]: 0.44-0.79, six trials involving 5486 participants), advanced adenoma (RR: 0.63, 95% CI: 0.43-0.92, four trials involving 4723 participants), and metachronous adenoma (RR: 0.58, 95% CI: 0.43-0.79, five trials involving 5258 participants) compared with placebo. Coxibs also significantly increased the risk of severe adverse events (RR: 1.29, 95% CI: 1.13-1.47, six trials involving 7109 participants). Other interventions, including Asp, folic acid, UDCA, vitamin D, and calcium, did not reduce the risk of colorectal adenoma in the general and high-risk populations compared with placebo.@*CONCLUSIONS@#Considering the balance between benefits and harms, regular use of coxibs for prevention of colorectal adenoma was not supported by the current evidence. Benefit of low-dose Asp for chemoprevention of colorectal adenoma still requires further evidence.@*REGISTRATION@#PROSPERO, No. CRD42022296376.

Acupuncture and moxibustion in treatment of chronic obstructive pulmonary disease at stable stage: a network Meta-analysis / 中国针灸

The efficacy on chronic obstructive pulmonary disease (COPD) at stable stage treated with different methods of acupuncture and moxibustion was evaluated using network Meta-analysis method. The articles of the randomized controlled trial (RCT) on stable COPD treated with acupuncture and moxibustion were searched electronically in CNKI, Wanfang, VIP, SinoMed, PubMed, EMbase, Web of Science and Cochrane library. The search was conducted from the inception of the databases to March 20th, 2022. Data analysis was performed using R4.1.1, Stata16.0 and RevMan5.3 softwares. A total of 48 RCTs were included, involving 15 kinds of acupuncture and moxibustion interventions and a sample size of 3 900 cases. The results of network Meta-analysis showed that: ① For the forced expiratory volume in one second predicted (FEV1%), both the governor vessel moxibustion combined with conventional treatment (G+C therapy) and the yang-supplementing moxibustion combined with conventional treatment (Y+C therapy) obtained the better effect than that of the conventional treatment (P<0.05), and the G+C therapy was more effective compared with the thread-embedding therapy combined with conventional treatment (E+C therapy) and warm needling (P<0.05). ② Concerning to COPD assessment test (CAT) score, the results indicated that the Y+C therapy, and the mild moxibustion combined with conventional treatment (M+C therapy) were more effective when compared with the conventional treatment (P<0.05), and the effect of the Y+C therapy was better than that of the E+C therapy (P<0.05). ③ Regarding six-minute walking distance (6MWD), the effect of acupuncture combined with conventional treatment (A+C therapy) was better than that of either the E+C therapy or the conventional treatment (P<0.05). The effect of the G+C therapy was optimal for improving FEV1%, the Y+C therapy obtained the best effect for improving CAT score, and A+C therapy was the most effective for improving 6MWD. Due to the limitation of the quality and quantity of included studies, this conclusion needs to be further verified through high-quality RCT.

Network meta-analysis comparing the clinical outcomes and safety of robotic, laparoscopic, and transanal total rectal mesenteric resection for rectal cancer / 中华胃肠外科杂志

Objective: To methodically assess the clinical effectiveness and safety of robot-assisted total rectal mesenteric resection (RTME), laparoscopic-assisted total rectal mesenteric resection (laTME), and transanal total rectal mesenteric resection (taTME). Methods: A computer search was conducted on PubMed, Embase, Cochrane Library, and Ovid databases to identify English-language reports published between January 2017 and January 2022 that compared the clinical efficacy of the three surgical procedures of RTME, laTME, and taTME. The quality of the studies was evaluated using the NOS and JADAD scales for retrospective cohort studies and randomized controlled trials, respectively. Direct meta-analysis and reticulated meta-analysis were performed using Review Manager software and R software, respectively. Results: Twenty-nine publications comprising 8,339 patients with rectal cancer were ultimately included. The direct meta-analysis indicated that the length of hospital stay was longer after RTME than after taTME, whereas according to the reticulated meta-analysis the length of hospital stay was shorter after taTME than after laTME (MD=-0.86, 95%CI: -1.70 to -0.096, P=0.036). Moreover, the incidence of anastomotic leak was lower after taTME than after RTME (OR=0.60, 95%CI: 0.39 to 0.91, P=0.018). The incidence of intestinal obstruction was also lower after taTME than after RTME (OR=0.55, 95%CI: 0.31 to 0.94, P=0.037). All of these differences were statistically significant (all P<0.05). There were no statistically significant differences between the three surgical procedures regarding the number of lymph nodes cleared, length of the inferior rectal margin, or rate of positive circumferential margins (all P>0.05). An inconsistency test using nodal analysis revealed no statistically significant differences between the results of direct and indirect comparisons of the six outcome indicators (all P>0.05). Furthermore, we detected no significant overall inconsistency between direct and indirect evidence. Conclusion: taTME has advantages over RTME and laTME, in terms of radical and surgical short-term outcomes in patients with rectal cancer.

Network Meta-analysis of Chinese medicine injection combined with conventional western medicine in treatment of stable angina pectoris / 中国中药杂志

This study aimed to systematically evaluate the efficacy and safety of different Chinese medicine injections combined with conventional western medicine for stable angina pectoris. PubMed, Cochrane Library, EMbase, Web of Science, CNKI, Wanfang, VIP, and SinoMed were searched to collect randomized controlled trial(RCT) of Chinese medicine injection combined with conventio-nal western medicine in the treatment of stable angina pectoris from the inception of the databases to July 8, 2022. Two researchers independently screened the literature, extracted the data, and evaluated the risk of bias of the included studies. Stata 15.1 was used for network Meta-analysis. A total of 52 RCTs were included, involving 4 828 patients treated by 9 Chinese medicine injections(Danhong Injection, Salvia Miltiorrhiza Polyphenol Hydrochloride Injection, Tanshinone Sodium Ⅱ_A Sulfonate Injection, Salvia Miltiorrhiza Ligustrazine Injection, Dazhu Hongjingtian Injection, Puerarin Injection, Safflower Yellow Pigment Injection, Shenmai Injection and Xuesaitong Injection). The network Meta-analysis showed that:(1)in terms of improving the efficacy of angina pectoris, the surface under the cumulative ranking curve(SUCRA) followed the order of conventional western medicine combined with Salvia Miltiorrhiza Ligustrazine Injection>Tanshinone Sodium Ⅱ_A Sulfonate Injection>Danhong Injection>Salvia Miltiorrhiza Polyphenol Hydrochloride Injection>Xuesaitong Injection>Shenmai Injection>Puerarin Injection>Safflower Yellow Pigment Injection>Dazhu Hongjingtian Injection;(2)in terms of improving the efficacy of electrocardiogram(ECG), SUCRA followed the order of conventional western medicine combined with Salvia Miltiorrhiza Ligustrazine Injection>Puerarin Injection>Danhong Injection>Salvia Miltiorrhiza Polyphenol Hydrochloride Injection>Shenmai Injection>Xuesaitong Injection>Safflower Yellow Pigment Injection>Tanshinone Sodium Ⅱ_A Sulfonate Injection>Dazhu Hongjingtian Injection;(3)in terms of increasing high-density lipoprotein cholesterol(HDL-C), SUCRA followed the order of conventional western medicine combined with Danhong Injection>Shenmai Injection>Safflower Yellow Pigment Injection>Xuesaitong Injection>Tanshinone Sodium Ⅱ_A Sulfonate Injection>Dazhu Hongjingtian Injection;(4)in terms of lowering low-density lipoprotein cholesterol(LDL-C), SUCRA followed the order of conventional western medicine combined with Safflower Yellow Pigment Injection>Danhong Injection>Shenmai Injection>Tanshinone Sodium Ⅱ_A Sulfonate Injection>Dazhu Hongjingtian Injection>Xuesaitong Injection;(5)in terms of safety, the overall adverse reactions of Chinese medicine injection combined with conventional western medicine were less than those of the control group. Current evidence indicated that Chinese medicine injection combined with conventional western medicine could improve the curative effect of stable angina pectoris with higher safety. Limited by the number and quality of included studies, the above conclusion needed to be verified by more high-quality studies.

Network Meta-analysis of single Hirudo prescriptions in treatment of ischemic cerebrovascular disease / 中国中药杂志

This study intended to evaluate the efficacy and safety of single Hirudo prescriptions in the treatment of ischemic cerebrovascular disease(ICVD) by frequency network Meta-analysis and traditional Meta-analysis. CNKI, Wanfang, VIP, SinoMed, PubMed, EMbase, and Cochrane Library databases were searched to collect the randomized controlled trial(RCT) of single Hirudo prescriptions for ICVD from the inception of the databases to May 2022. The quality of the included literature was evaluated by Cochrane risk of bias tool. Finally, 54 RCTs and 3 single Hirudo prescriptions were included. Statistical analysis was conducted by RevMan 5.3 and Stata SE 15. Network Meta-analysis showed that in terms of the clinical effective rate, the surface under the cumulative ranking curve(SUCRA) of intervention measures was as follows: Huoxue Tongmai Capsules+conventional treatment>Maixuekang Capsules+conventional treatment>Naoxuekang Capsules+conventional treatment>conventional treatment. Traditional Meta-analysis revealed that in terms of the safety of ICVD treatment, Maixuekang Capsules+conventional treatment had higher safety than conventional treatment alone. According to the network Meta-analysis and traditional Meta-analysis, it was found that conventional treatment combined with single Hirudo prescriptions improved the clinical efficacy of ICVD patients, and compared with that of conventional treatment alone, the incidence of adverse reactions of combined treatment was low and the safety was high. However, the methodological quality of the articles included in this study was generally low and there were large differences in the number of articles on the three combined medication. Therefore, the conclusion of this study needed to be confirmed by subsequent RCT.

Network Meta-analysis of Chinese patent medicine containing Hirudo in treatment of atherosclerosis / 中国中药杂志

This study aimed to evaluate the efficacy and safety of Chinese patent medicines containing Hirudo in the treatment of atherosclerosis(AS) by network Meta-analysis, and to provide evidence-based reference for clinical treatment of AS. The clinical randomized controlled trial(RCT) on the treatment of atherosclerosis with Chinese patent medicines containing Hirudo were searched in CNKI, Wanfang, VIP, SinoMed, PubMed and EMbase from the establishment of the databases to July 1, 2022. And data extraction and quality assessment of the included RCT was performed according to the Cochrane standards. Stata 17 and ADDIS 1.16.5 were then used for Bayesian model network Meta-analysis. Finally, 67 RCTs with a total sample size of 6 826 cases were included, 3 569 cases in the experimental group and 3 257 cases in the control group, involving three oral Chinese patent medicines. Network Meta-analysis showed that in terms of reducing intima-media thickness(IMT), the top three Chinese patent medicines were Tongxinluo Capsules+sta-tins>Maixuekang Capsules+statins>Maixuekang Capsules. In terms of reducing plaque area, the top one was Maixuekang Capsules+sta-tins, and the other Chinese patent medicines had similar efficacy. For lowering AS Crouse scores, the top three were Maixuekang Capsules>Tongxinluo Capsules+statins>Naoxintong Capsules. For decreasing plaque number, the top three were Naoxintong Capsules+sta-tins>Tongxinluo Capsules+statins>Tongxinluo Capsules. With regard to adverse reactions/events, Naoxintong Capsules+statins had the lo-west incidence. In conclusion, in Chinese patent medicines containing Hirudo for the treatment of AS, Tongxinluo Capsules+statins, Maixuekang Capsules, Maixuekang Capsules+statins, and Naoxintong Capsules+statins were the primary choices to reduce IMT, AS Crouse scores, plaque area, and plaque number, respectively. The efficacy of Chinese patent medicines containing Hirudo with or without statins was more significant than that of statins alone in the four outcome indexes. Additionally, the treatment of AS should be evaluated comprehensively, and attention should be paid to Chinese patent medicines or their combination with western medicine, to optimize the treatment effect and minimize adverse reactions as the benchmark.

Immunogenicity and reactogenicity of heterologous immunization schedules with COVID-19 vaccines: a systematic review and network meta-analysis / 中华医学杂志(英文版)

BACKGROUND@#Data on the immunogenicity and safety of heterologous immunization schedules are inconsistent. This study aimed to evaluate the immunogenicity and safety of homologous and heterologous immunization schedules.@*METHODS@#Multiple databases with relevant studies were searched with an end date of October 31, 2021, and a website including a series of Coronavirus disease 2019 studies was examined for studies before March 31, 2022. Randomized controlled trials (RCTs) that compared different heterologous and homologous regimens among adults that reported immunogenicity and safety outcomes were reviewed. Primary outcomes included neutralizing antibodies against the original strain and serious adverse events (SAEs). A network meta-analysis (NMA) was conducted using a random-effects model.@*RESULTS@#In all, 11 RCTs were included in the systematic review, and nine were ultimately included in the NMA. Among participants who received two doses of CoronaVac, another dose of mRNA or a non-replicating viral vector vaccine resulted in a significantly higher level of neutralizing antibody than a third CoronaVac 600 sino unit (SU); a dose of BNT162b2 induced the highest geometric mean ratio (GMR) of 15.24, 95% confidence interval [CI]: 9.53-24.39. Following one dose of BNT162b2 vaccination, a dose of mRNA-1273 generated a significantly higher level of neutralizing antibody than BNT162b2 alone (GMR = 1.32; 95% CI: 1.06-1.64), NVX-CoV2373 (GMR = 1.60; 95% CI: 1.16-2.21), or ChAdOx1 (GMR = 1.80; 95% CI: 1.25-2.59). Following one dose of ChAdOx1, a dose of mRNA-1273 was also more effective for improving antibody levels than ChAdOx1 (GMR = 11.09; 95% CI: 8.36-14.71) or NVX-CoV2373 (GMR = 2.87; 95% CI: 1.08-3.91). No significant difference in the risk for SAEs was found in any comparisons.@*CONCLUSIONS@#Relative to vaccination with two doses of CoronaVac, a dose of BNT162b2 as a booster substantially enhances immunogenicity reactions and has a relatively acceptable risk for SAEs relative to other vaccines. For primary vaccination, schedules including mRNA vaccines induce a greater immune response. However, the comparatively higher risk for local and systemic adverse events introduced by mRNA vaccines should be noted.@*REGISTRATION@#PROSPERO; https://www.crd.york.ac.uk/PROSPERO/ ; No. CRD42021278149.

Ablation therapies for paroxysmal atrial fibrillation: A systematic review and patient-level network meta-analysis

INTRODUCTION@#Despite promising trials, catheter ablation is still regarded as an adjunct to antiarrhythmic drugs (AADs) in the treatment of paroxysmal atrial fibrillation (PAF). This study aimed to compare the effectiveness of various ablation therapies and AADs.@*METHOD@#Randomised controlled trials or propensity score-matched studies comparing atrial tachyarrhythmia recurrence among any combination of ablation modalities or AAD were retrieved. Kaplan-Meier curves and risk tables for this outcome were graphically reconstructed to extract patient-level data. Frequentist network meta-analysis (NMA) using derived hazard ratios (HRs), as well as 2 restricted mean survival time (RMST) NMAs, were conducted. Treatment strategies were ranked using P-scores.@*RESULTS@#Across 24 studies comparing 6 ablation therapies (5,132 patients), Frequentist NMA-derived HRs of atrial fibrillation recurrence compared to AAD were 0.35 (95% confidence interval [CI]=0.25-0.48) for cryoballoon ablation (CBA), 0.34 (95% CI=0.25-0.47) for radiofrequency ablation (RFA), 0.14 (95% CI=0.07-0.30) for combined CBA and RFA, 0.20 (95% CI=0.10-0.41) for hot-balloon ablation, 0.43 (95% CI=0.15-1.26) for laser-balloon ablation (LBA), and 0.33 (95% CI=0.18-0.62) for pulmonary vein ablation catheter. RMST-based NMAs similarly showed significant benefit of all ablation therapies over AAD. The combination of CBA + RFA showed promising long-term superiority over CBA and RFA, while LBA showed favourable short-term efficacy.@*CONCLUSION@#The advantage of ablation therapies over AAD in preventing atrial tachyarrhythmia recurrence suggests that ablation should be considered as the first-line treatment for PAF in patients fit for the procedure. The promising nature of several specific therapies warrants further trials to elicit their long-term efficacy and perform a cost-benefit analysis.

Network Meta-analysis of Qi-supplementing and Yin-nourishing Chinese patent medicines in treatment of early diabetic nephropathy / 中国中药杂志

This study aimed to evaluate the efficacy of Qi-supplementing and Yin-nourishing Chinese patent medicine in the treatment of early diabetic nephropathy(DN) by network Meta-analysis to explore the Chinese patent medicine with optimal efficacy and provide references for preventing renal deterioration and delaying the progression of early DN. Eight databases, including CNKI, Wanfang, VIP, SinoMed, PubMed, EMbase, Cochrane Library, and Web of Science, were searched for clinical randomized controlled trial(RCT) of Qi-supplementing and Yin-nourishing Chinese patent medicines in the treatment of early DN. After the literature mee-ting the inclusion criteria was screened, the quality of the literature was evaluated using the Cochrane risk-of-bias tool, and network Meta-analysis was performed using the BUGSnet package in R 4.2.1. Seventy-two research articles with a sample size of 6 344 cases were included, involving eight Chinese patent medicines and seven outcome indicators. The results of the network Meta-analysis showed that(1)in terms of improving urinary albumin excretion rate(UAER), Chinese patent medicines combined with conventional treatment were superior to conventional treatment, and Qiyao Xiaoke Capsules + conventional treatment was optimal.(2)In terms of reducing serum crea-tinine(Scr), Bailing Capsules + conventional treatment had superior efficacy.(3)In terms of reducing 24-hour urine total protein(24hUTP), Shenyan Kangfu Tablets + conventional treatment and Jinshuibao Capsules + conventional treatment had equivalent efficacy, and Shenyan Kangfu Tablets + conventional treatment was superior.(4)In terms of improving fasting blood glucose(FBG), Shenyan Kangfu Tablets + conventional treatment had superior efficacy.(5)In terms of improving total cholesterol(TC), Qiyao Xiaoke Capsules +conventional treatment had superior efficacy.(6)In terms of reducing triglyceride(TG), Bailing Capsules + conventional treatment had superior efficacy.(7)In terms of safety, the occurrence of adverse reactions was reported in seven interventions, but due to the large clinical heterogeneity, the quantitative analysis could not be performed. Overall, Qi-supplementing and Yin-nourishing Chinese patent medicines combined with conventional treatment were superior to conventional treatment alone in the treatment of early DN. The results showed that Qi-supplementing and Yin-nourishing Chinese patent medicines combined with conventional treatment had good clinical efficacy, and they could significantly reduce renal function indicators such as UAER, Scr, and 24hUTP, and reduce blood sugar and blood lipid, which can provide evidence-based support for the treatment of early DN. However, due to the differences in the quantity and quality of the included research articles, large-sample, multi-center, high-quality studies are still needed for further verification.

Network Meta-analysis of oral Chinese patent medicine in adjuvant treatment of rotavirus gastroenteritis in children / 中国中药杂志

This study aimed to evaluate the efficacy and safety of various oral Chinese patent medicines in the adjuvant treatment of rotavirus gastroenteritis(RVGE) in children based on network Meta-analysis. Randomized controlled trial(RCT) of oral Chinese patent medicine in the adjuvant treatment of RVGE in children was retrieved from the databases such as CNKI, Wanfang, VIP, SinoMed, PubMed, Cochrane Library, EMbase, and Web of Science from database inception to October 22, 2022. The quality of the included RCT was evaluated according to the Cochrane risk-of-bias tool, and the data were analyzed by RevMan 5.4 and Stata 16 software. Sixty-three RCTs were included, with 11 oral Chinese patent medicines involved, including Xingpi Yanger Granules, Weichang'an Pills, Qiuxieling Mixture, Erxieting Granules, and Changyanning Granules/Syrup. The results of the network Meta-analysis showed that in terms of clinical total effective rate, the top 3 optimal interventions were Changyanning Granules/Syrup, Xiaoer Guangpo Zhixie Oral Liquid, and Xiaoer Shuangjie Zhixie Granules combined with conventional western medicine. In terms of the anti-diarrheal time, the top 3 optimal interventions were Shenling Baizhu Granules, Qiuxieling Mixture, and Shuangling Zhixie Oral Liquid combined with conventional western medicine. In terms of the antiemetic time, the top 3 optimal interventions were Changyanning Granules/Syrup, Xingpi Yanger Granules, and Xiaoer Shuangjie Zhixie Granules combined with conventional western medicine. In terms of the antipyretic time, the top 3 optimal interventions were Shenling Baizhu Granules, Xiaoer Shuangjie Zhixie Granules, and Qiuxieling Mixture combined with conventional western medicine. In terms of the negative conversion rate of rotavirus, the top 3 optimal interventions were Xingpi Yanger Granules, Erxieting Granules, and Cangling Zhixie Oral Liquid combined with conventional western medicine. In terms of reducing creatine kinase isoenzyme MB(CK-MB) level, the top 3 optimal interventions were Weichang'an Pills, Xingpi Yanger Granules, and Xiaoer Shuangjie Zhixie Granules combined with conventional western medicine. In terms of adverse reactions, no se-rious adverse reactions were reported in all studies. Oral Chinese patent medicines in the adjuvant treatment of children with RVGE have their own advantages, Specifically, Changyanning Granules/Syrup + conventional western medicine focuses on improving the clinical total effective rate and shortening the antiemetic time, Shenling Baizhu Granules + conventional western medicine on shortening the anti-diarrheal time and antipyretic time, Xingpi Yanger Granules + conventional western medicine on improving the negative conversion rate of rotavirus, and Weichang'an Pills + conventional western medicine on reducing the CK-MB level. Limited by the quantity and quality of literature included in this study, the results need to be verified by high-quality RCT with a larger sample size.

Network Meta-analysis of Chinese patent medicines in treatment of idiopathic membranous nephropathy / 中国中药杂志

This study aimed to systematically evaluate the efficacy and safety of different Chinese patent medicines in the treatment of idiopathic membranous nephropathy. The relevant randomized controlled trial(RCT) was retrieved from PubMed, EMbase, Cochrane Library, CNKI, SinoMed, Wanfang, and VIP with the time interval from database inception to December 2022. The Cochrane risk of bias assessment tool was employed to evaluate the quality of the included RCT, and Stata 15.0 and GEMTC to perform the Bayesian network Meta-analysis. Finally, 51 RCTs were included, involving 9 Chinese patent medicines and 3 591 patients. The results of network Meta-analysis showed that in terms of the total effective rate and the increase in plasma albumin, the top three interventions were Zhengqing Fengtongning Sustained Release Tablets + conventional western medicine, Bailing Capsules + conventional western medicine, and Tripterygium Glycosides Tablets + conventional western medicine. In terms of reducing 24-hour urine total protein, the top three interventions were Zhengqing Fengtongning Sustained Release Tablets + conventional western medicine, Shenfukang Capsules +conventional western medicine, and Huangkui Capsules + conventional western medicine. In terms of reducing serum creatinine, the top three interventions were Shenfukang Capsules + conventional western medicine, Bailing Capsules + conventional western medicine, and Zhengqing Fengtongning Sustained Release Tablets + conventional western medicine. In terms of safety, Chinese patent medicines combined with conventional western medicine had fewer adverse reactions than the control group. The results suggest that Chinese patent medicines combined with conventional western medicine can improve the therapeutic effect on idiopathic membranous nephropathy, and differentiated medications can be adopted according to the specific symptoms of patients in clinical treatment. Further validation needs to be carried out in the future with multi-center, large-sample, and high-quality RCT.

Network Meta-analysis of efficacy of Chinese patent medicine in treatment of inflammatory response in diabetic nephropathy / 中国中药杂志

This study aimed to evaluate the efficacy and safety of various Chinese patent medicines in the treatment of inflammatory response in diabetic nephropathy(DN) based on network Meta-analysis. Randomized controlled trial(RCT) of oral Chinese patent medicines for improving inflammatory response in patients with DN was retrieved from CNKI, Wanfang, VIP, SinoMed, PubMed, Cochrane Library, EMbase, Web of Science, and other databases from database inception to October 2022. All investigators independently screened the literature, extracted data, and evaluated the quality. Stata 16.0 software and RevMan 5.4.1 were used to analyze the data of the literature that met the quality standards. Finally, 53 RCTs were included, involving 6 Chinese patent medicines. The total sample size was 4 891 cases, including 2 449 cases in the test group and 2 442 cases in the control group. The network Meta-analysis showed that(1) in terms of reducing TNF-α, the top 3 optimal interventions according to the surface under the cumulative ranking curve(SUCRA) were Shenshuaining Capsules/Granules/Tablets + conventional western medicine, Jinshuibao Capsules + conventional western medicine, and Niaoduqing Granules + conventional western medicine.(2) In terms of reducing hs-CRP, the top 3 optimal interventions according to SUCRA were Bailing Capsules + conventional western medicine, Tripterygium Glycosides Tablets + conventional western medicine, and Shenshuaining Capsules/Granules/Tablets + conventional western medicine.(3) In terms of reducing IL-6, the top 3 optimal interventions according to SUCRA were Bailing Capsules + conventional western medicine, Tripterygium Glycosides Tablets + conventional western medicine, and Jinshuibao Capsules + conventional western medicine.(4) In terms of reducing UAER, the top 3 optimal interventions according to SUCRA were Shenshuaining Capsules/Granules/Tablets + conventional western medicine, Huangkui Capsules + conventional western medicine, and Jinshuibao Capsules + conventional western medicine.(5) In terms of reducing Scr, the top 3 optimal interventions according to SUCRA were Jinshuibao Capsules + conventional western medicine, Niaoduqing Granules + conventional wes-tern medicine, and Tripterygium Glycosides Tablets + conventional western medicine.(6) In terms of reducing BUN, the first 3 optimal interventions according to SUCRA were Niaoduqing Granules + conventional western medicine, Tripterygium Glycosides Tablets + conventional western medicine, and Huangkui Capsules + conventional western medicine.(7) In terms of improving the clinical total effective rate, the first 3 optimal interventions according to SUCRA were Jinshuibao Capsules + conventional western medicine, Niaoduqing Granu-les + conventional western medicine, and Huangkui Capsules + conventional western medicine. The results showed that the combination of western medicine and Chinese patent medicine could reduce the expression of serum inflammatory factors TNF-α, hs-CRP, and IL-6 and inhibit the inflammatory response. The combination of western medicine and Chinese patent medicine was superior to western medicine alone in reducing Scr, BUN, and UAER, and improving the total effective rate of treatment. Due to the limitation of the quantity and quality of literature included, the above conclusions need to be validated by more high-quality studies.

Network Meta-analysis of oral Chinese patent medicines in treatment of acute exacerbation of chronic obstructive pulmonary disease / 中国中药杂志

This study aimed to evaluate the effectiveness and safety of eight oral Chinese patent medicines in the treatment of acute exacerbation of chronic obstructive pulmonary disease(AECOPD) by network Meta-analysis. Randomized controlled trial(RCT) on the treatment of AECOPD with eight oral Chinese patent medicines was retrieved from databases including CNKI, Wanfang, VIP, SinoMed, PubMed, Web of Science, EMbase, and Cochrane Library from database inception to August 6, 2022. The information was extracted from the included literature and the quality of the included studies was evaluated using the Cochrane risk of bias assessment tool. The data were analyzed using Stata SE 15.1 and ADDIS 1.16.8 software. Finally, 53 RCTs were included, with 5 289 patients involved, including 2 652 patients in the experimental group and 2 637 patients in the control group. Network Meta-analysis showed that Lianhua Qingwen Capsules+conventional western medicine were optimal in improving clinical effective rate, Shufeng Jiedu Capsules+conventional western medicine in improving FEV1/FVC, Qingqi Huatan Pills+conventional western medicine in improving FEV1%pred, Feilike Mixture(Capsules)+conventional western medicine in improving PaO_2, Lianhua Qingwen Capsules+conventional western medicine in reducing PaCO_2, and Qingqi Huatan Pills+conventional western medicine in reducing C-reactive protein(CRP). In terms of safety, most of them were gastrointestinal symptoms, and no serious adverse reactions were reported. When the clinical effective rate was taken as the comprehensive index of efficacy evaluation, Lianhua Qingwen Capsules+conventional western medicine were the most likely to be the best treatment for AECOPD. There are some limitations in the conclusion of this study. It only provides references for clinical medication.

Network Meta-analysis of Qi-benefiting and blood-activating Chinese patent medicines against ischemic stroke / 中国中药杂志

This study aimed to compare the efficacy of Qi-benefiting and blood-activating Chinese patent medicines in the treatment of ischemic stroke with network Meta-analysis. CNKI, Wanfang, VIP, SinoMed, PubMed, EMbase, and Cochrane Library were searched from database inception to October 2022 for randomized controlled trial(RCT) on 11 Qi-benefiting and blood-activating Chinese patent medicines in the treatment of ischemic stroke. The risk of bias plot was made by RevMan 5.3, and network Meta-analysis and efficacy ranking were performed by Stata 17. Ninety-two RCTs were included, involving 10 608 patients. According to the network Meta-analysis, in terms of the clinical total effective rate, surface under the cumulative ranking curve(SUCRA) as followed: Qilong Capsules+conventional western medicine>Zhishe Tongluo Capsules+conventional western medicine>Longshengzhi Capsules+conventional western medicine>Naoxintong Capsules+conventional western medicine>Tongsaimai Tablets+conventional western medicine>Naoan Capsules+conventional western medicine>Naoluotong Capsules+conventional western medicine>Xiaoshuan Changrong Capsules+conventional western medicine>Dengzhan Shengmai Capsules+conventional western medicine=Tongxinluo Capsules+conventional western medicine>Naomaitai Capsules+conventional western medicine. In terms of the improvement in National Institute of Health stroke scale(NIHSS) score, SUCRA as followed: Longshengzhi Capsules+conventional western medicine>Naomaitai Capsules+conventional western medicine>Naoxintong Capsules+conventional western medicine>Dengzhan Shengmai Capsules+conventional western medicine>Xiaoshuan Changrong Capsules+conventional western medicine>Naoluotong Capsules+conventional western medi-cine>Tongxinluo Capsules+conventional western medicine>Naoan Capsules+conventional western medicine>Qilong Capsules+conventional western medicine. In terms of safety, the overall adverse reactions/events of Qi-benefiting and blood-activating Chinese patent medicines + conventional western medicine were less than those of the control group. Since Qilong Capsules+conventional western medicine and Zhishe Tongluo Capsules+conventional western medicine were preferred to improve the clinical total effective rate. In the aspect of improving NIHSS score, Longshengzhi Capsules+conventional western medicine and Naomaitai Capsules+conventional western medicine were first options. Due to the lack of direct comparisons between drugs, the overall quality of RCT was not high, so more studies are needed to verify the strength of the evidence.

Walkability and physical activity: a protocol for systematic review and meta-analysis / Associação entre walkability e atividade física: um protocolo para revisão sistemática e meta-análise

The appropriate area for walking, related to the flow of walking, on the sidewalks and crossing (walka-bility) influences the practice of physical activity. However, there is no evidence of meta-analyses that have evaluated this association. Therefore, this study presents a protocol to assess the association be-tween walkability and physical activity. The systematic review protocol was conducted following the PRISMA 2020 guidelines and will includes a search in the following databases: PubMed, SPORT-Discus, LILACS, Web of Science, Scopus, Embase, and Cochrane. It will include observational studies, cross-sectional and longitudinal, that assessed the association between walkability in the neighborhood and physical activity. The process of study selection will be conducted independently by two reviewers. The process will start by reading the titles and abstracts of interest, followed by the full reading of the articles through the Rayyan platform. We will assess the methodological and indi-vidual quality across the studies utilizing the Newcastle Ottawa Scale (NOS) and the Chi-Squared test (I2). To test the influence of variables in the meta-analysis results, we will use, whenever possible, the meta-regression technique. The meta-analysis results will be presented as Odds Ratio (OR) with 95% confidence interval, through a random or fixed-effects model, according to estimate of clinical, statistical, and methodological heterogeneity. If possible, stratifications will be performed according to age group, sex, and physical activity levels.With the expected results, we hope that the knowledge will be useful to encourage the implementation of public policies for walkability in the neighborhood to increase physical activity levels

A área adequada para caminhada, relacionada ao fluxo de caminhada, nas calçadas e travessias (walkability) influencia na prática de atividade física. No entanto, não há evidências de meta-análises que tenham avaliado essa associação. Portanto, este estudo apresenta um protocolo para avaliar a as-sociação entre walkability e atividade física. O protocolo de revisão sistemática será realizado seguin-do as recomendações do PRISMA 2020 e incluirá uma busca nas seguintes bases de dados: PubMed, SPORTDiscus, LILACS, Web of Science, Scopus, Embase e Cochrane. Serão incluídos estudos observacionais, transversais e longitudinais, que avaliaram a associação entre walkability na vizinhan-ça e atividade física. O processo de seleção dos estudos será conduzido de forma independente por dois revisores. O processo terá início pela leitura dos títulos e resumos de interesse, seguido da leitura completa dos artigos por meio da plataforma Rayyan. Avaliaremos a qualidade metodológica e in-dividual entre os estudos utilizando a Escala de Newcastle Ottawa (NOS) e o teste Qui-Quadrado (I2). Para testar a influência das variáveis nos resultados da meta-análise, utilizaremos, sempre que possível, a técnica de meta-regressão. Os resultados da meta-análise serão apresentados como Odds Ratio (OR) com intervalo de confiança de 95%, por meio de um modelo de efeitos aleatórios ou fixos, de acordo com a estimativa clínica, estatística e metodológica da heterogeneidade. Se possível, serão realizadas estratificações de acordo com faixa etária, sexo e níveis de atividade física. Com os resulta-dos do estudo, esperamos que o conhecimento seja útil para incentivar a implementação de políticas públicas de walkability no bairro para aumentar os níveis de atividade física

Network Meta-analysis of efficacy and safety of oral Chinese patent medicines combined with conventional western medicine in treatment of hypertension / 中国中药杂志

This study aims to systematically evaluate the effect of oral Chinese patent medicines on hypertension with network Meta-analysis. Randomized controlled trials on the treatment of hypertension with oral Chinese patent medicine combined with conventional western medicine were retrieved from China National Knowledge Infrastructure(CNKI), Wanfang, VIP, SinoMed, PubMed, EMbase, and Cochrane Library(from establishment of the database to August 2021). Two researchers independently screened the articles, extracted the data, and evaluated article quality. Then R 4.1.0 was employed for data analysis. Finally, 195 eligible articles were screened out, involving 22 546 patients and 18 oral Chinese patent medicines. The results of the network Meta-analysis are as follows. In terms of reducing systolic blood pressure(SBP) and diastolic blood pressure(DBP), Xuesaitong, Qiangli Dingxuan Tablets, Songling Xuemaikang Capsules combined with conventional western medicine are superior. In improving blood lipids, the overall effects of Xinmaitong Capsules, Compound Xueshuantong Capsules, Ginkgo Folium preparations, Yindan Xinnaotong Soft Capsules, and Naoxintong Capsules combined with conventional western medicine are outstanding. In terms of regulating endothelial function, Yindan Xinnaotong Soft Capsules, Xinmaitong Capsules, Zhenju Jiangya Tablets, Compound Danshen Dripping Pills, Xuesaitong with conventional western medicine have certain advantages. As for the safety, the incidence of adverse reactions of conventional western medicine combined with oral Chinese patent medicines is lower than that of conventional western medicine alone. In summary, compared with conventional western medicine alone, the 18 oral Chinese patent medicines combined with conventional western medicine in the treatment of hypertension show advantages in improving blood pressure, blood lipids, and endothelial function. Among them, Xuesaitong, Qiangli Dingxuan Tablets, and Songling Xuemaikang Capsules may be the best oral Chinese patent medicines for lowering blood pressure. The conclusion needs to be further verified by more high-quality studies.

Network Meta-analysis of efficacy and safety of Chinese patent medicines in treatment of ankylosing spondylitis / 中国中药杂志

To evaluate the efficacy and safety of Chinese patent medicines in the treatment of ankylosing spondylitis(AS) by frequency network Meta-analysis. Randomized controlled trials(RCTs)of Chinese patent medicines for AS were retrieved from CNKI, Wanfang, VIP, CBM, PubMed, EMbase and Cochrane Library databases from the time of database establishment to January 2021. The quality of the included RCTs was evaluated according to the Cochrane bias risk standard, and the data was analyzed by RevMan 5.3 and Stata/MP 15.1. A total of 12 kinds of Chinese patent medicines in 55 RCTs were included. According to Meta-analysis, in term of the effectiveness, the top three optimal medication regimens were Biqi Capsules, Yishen Juanbi Pills and Yaobitong Capsules combined with western medicine. The top three interventions to reduce the erythrocyte sedimentation rate(ESR)were Yishen Juanbi Pills, Xianling Gubao Capsules and Fufang Xuanju Capsules combined with western medicine. The top three interventions to reduce the C-reactive protein(CRP)were Biqi Capsules, Xianling Gubao Capsules and Fufang Xuanju Capsules combined with western medicine. In terms of the safety, top three optimal medication regimens were Total Glucosides of Paeony Capsules, Yishen Juanbi Pills, and Wangbi Tablets combined with western medicine. This network Meta-analysis suggests that Chinese patent medicines combined with conventional western medicine can effectively improve the joint pain symptoms of AS patients and reduce the acute inflammatory indicators, with high safety. However, the literature included in this study is generally of low methodological quality, and the conclusion needs to be verified by high-quality research.

Network Meta-analysis of oral blood-activating and stasis-removing Chinese patent medicines in treatment of hypertensive left ventricular hypertrophy / 中国中药杂志

This study was designed to assess the clinical efficacy of oral blood-activating and stasis-removing Chinese patent medicines in treating hypertensive left ventricular hypertrophy(LVH) based on network Meta-analysis. The clinical randomized controlled trials(RCTs) concerning the treatment of hypertensive LVH with oral blood-activating and stasis-removing Chinese patent medicines were retrieved from CNKI, Wanfang, VIP, SinoMed, PubMed, Web of Science, and Cochrane Library from their inception to September 2021. Two researchers independently completed the literature screening, data extraction, and quality evaluation. The data were then analyzed by RevMan 5.3, Stata 15.1, and ADDIS 1.16.8. Finally, a total of 31 RCTs were included, involving 3 001 patients and four oral blood-activating and stasis-removing Chinese patent medicines. In terms of the alleviation of heart damage, the Chinese patent medicines combined with conventional western medicine groups were superior to the conventional western medicine groups in lo-wering the left ventricular mass index(LVMI). There was no significant difference in LVMI, left ventricular ejection fraction(LVEF), or the ratio of early diastolic peak flow velocity to late diastolic peak flow velocity(E/A) between different Chinese patent medicines combined with conventional western medicine groups. Xinnao Shutong Capsules/Tablets combined with conventional western medicine had the best efficacy in reducing LVMI and elevating LVEF, while Xinkeshu Capsules/Tablets combined with conventional western medicine had the best effect in improving E/A. In the control of blood pressure, when all Chinese patent medicines except for Xinnao Shutong Capsules/Tablets were combined with conventional western medicine, the resulting systolic blood pressure(SBP) and diastolic blood pressure(DBP) were significantly lower than those in the conventional western medicine group. Xinkeshu Capsules/Tablets combined with conventional western medicine produced the best effect in reducing SBP and DBP, followed by Xinnao Shutong Capsules/Tablets. In terms of safety, no serious adverse reactions occurred in all trials. The four oral blood-activating and stasis-removing Chinese patent medicines included in this study exhibited obvious advantages in the treatment of hypertensive LVH when they were combined with conventional western medicine, with the best effects observed in the Xinnao Shutong Capsules/Tablets combined with conventional western medicine group. However, due to the limitation of the quantity and quality of the included articles, the conclusion of this study still needs to be verified by more high-quality, multi-center, and large-sample RCTs.