Prophylaxis regimens for GVHD: systematic review and meta-analysis

Opinions are divided regarding the best prophylactic regimen for GVHD. The aim of this study was to evaluate potential survival benefit of different prophylactic regimens for acute GVHD (aGVHD). We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) including patients undergoing Allo-SCT. We included trials that assessed the addition of MTX, compared CsA and tacrolimus and evaluated the addition of steroids. Outcomes assessed were all-cause mortality (ACM) at the longest follow-up, aGVHD, chronic GVHD, TRM, relapse rate and regimen-specific adverse events. Relative risks (RRs) with 95% confidence intervals (CIs) were estimated and pooled. The regimen of MTX-CsA vs CsA alone (four trials) yielded no statistically significant difference in ACM (RR=0.84 (0.61-1.14)), but a significant decrease in aGVHD (RR=0.52 (0.39-0.7)). There was no difference in ACM for the comparison of MTX-CsA and MTX-tacrolimus (three trials); however, MTX-tacrolimus was superior to MTX-CsA in the reduction of aGVHD (RR=0.62 (0.52-0.75)) and severe aGVHD (RR=0.67 (0.47-0.95)). The addition of steroids did not affect the outcomes (four trials). We conclude that MTX-CsA and MTX-tacrolimus are both acceptable alternatives for GVHD prophylaxis, although MTX-tacrolimus may be superior in terms of aGVHD reduction.     

Comparative cost-effectiveness of antiviral therapies in patients with chronic hepatitis B: a systematic review of economic evidence

BACKGROUND AND AIM: Economic efficiency of the alternative antiviral therapies for chronic hepatitis B has not been systematically investigated and their quality remains unknown. The aim of the present study was to systematically overview economic evidence of antiviral therapies for chronic hepatitis B. METHODS: We searched six databases and eight major journals supplemented with screening references of eligible studies. Full economic evaluations comparing alternative antiviral therapies in patients with chronic hepatitis B virus infection were included. Two investigators assessed the study quality and transferability, independently. Data were analyzed qualitatively with adjustment when appropriate. RESULTS: Fourteen studies (six modeling vs eight trials and database analyses) were included. Quality was high in five studies, moderate in one US and five Chinese studies, and low in three Chinese studies. The major problems of quality are costing methods and analysis and the presentation of results. In Australia and Poland, lamivudine-preferred strategies dominated interferon (IFN)-alpha and its related strategy from the health-care sector perspective. In the US, adefovir salvage produced US$8446 per additional quality-adjusted life years (QALY) compared with IFN-alpha. In Spain, the cost of adefovir was US$34,840 for additional virological response. In Taiwan, the use of pegylated IFN-alpha (pegIFN-alpha) produced US$11,711.4 per additional QALY, compared with lamivudine. In China, the incremental cost-effectiveness ratios of combination therapy lamivudine ranged from US$2860 to US$22,160 per additional loss of hepatitis B e antigen (HBeAg), and IFN-alpha versus lamivudine ranged from US$2490 to US$8890 per additional loss of HBeAg. CONCLUSION: The cost-effectiveness frontiers of treatment alternatives vary and are influenced by the comparators and socioeconomic conditions of countries. Lamivudine-containing therapy is cost-effective when newer antiviral agents (e.g. adefovir/pegIFN-alpha) were not available. Economic methods should be further improved in studies, particularly in China.     

Hepatitis B reactivation in patients receiving direct-acting antiviral therapy or interferon-based therapy for hepatitis C:A systematic review and meta-analysis

AIM To assess the incidence of hepatitis B virus(HBV) reactivation in patients receiving direct-acting antiviral agent(DAA)-based therapy or interferon(IFN)-based therapy for hepatitis C and the effectiveness of preemptive antiHBV therapy for preventing HBV reactivation.METHODS The Pub Med, MEDLINE and EMBASE databases were searched, and 39 studies that reported HBV reactivation in HBV/hepatitis C virus coinfected patients receiving DAAbased therapy or IFN-based therapy were included. The primary outcome was the rate of HBV reactivation. The secondary outcomes included HBV reactivation-related hepatitis and the effectiveness of preemptive anti-HBV treatment with nucleos(t)ide analogues. The pooled effects were assessed using a random effects model. RESULTS The rate of HBV reactivation was 21.1% in hepatitis Bsurface antigen(HBs Ag)-positive patients receiving DAAbased therapy and 11.9% in those receiving IFN-based therapy. The incidence of hepatitis was lower in HBs Agpositive patients with undetectable HBV DNA compared to patients with detectable HBV DNA receiving DAA therapy(RR = 0.20, 95%CI: 0.06-0.64, P = 0.007). The pooled HBV reactivation rate in patients with previous HBV infection was 0.6% for those receiving DAA-based therapy and 0 for those receiving IFN-based therapy, and none of the patients experienced a hepatitis flare related to HBV reactivation. Preemptive anti-HBV treatment significantly reduced the potential risk of HBV reactivation in HBs Agpositive patients undergoing DAA-based therapy(RR = 0.31, 95%CI: 0.1-0.96, P = 0.042).CONCLUSION The rate of HBV reactivation and hepatitis flare occurrence is higher in HBs Ag-positive patients receiving DAA-based therapy than in those receiving IFN-based therapy, but these events occur less frequently in patients with previous HBV infection. Preemptive anti-HBV treatment is effective in preventing HBV reactivation.     

替比夫定治疗慢性乙型肝炎疗效的系统评价

目的:系统评价替比夫定(LDT)治疗慢性乙型肝炎(CHB)的治疗效果.方法:应用Cochrane系统评价方法计算机检索Cochrane Library(2009年第3期)、PubMed(1966-2009.9)、EMBASE(1974-2009.9)、中国生物医学数据库(CBM,1978-2009.9)、中国期刊全文数据库(CNKI,1979-2009.9)和维普数据库(VIP,1989-2009.9),同时在临床试验注册网站及Google搜索引擎进行检索,并追查纳入研究参考文献,收集以LDT治疗CHB的所有随机对照试验(RCT)和交叉试验.根据Cochrane协作网推荐的风险评估工具进行风险偏倚评估,用RevMan5.0软件进行统计学分析.结果:最终纳入10个RCTs,共4037例患者.7篇LDT对比拉米夫定(LAM)的研究结果显示,对于HBeAg阳性患者,LDT组较LAM组更有效提高血清HBVDNA检测不到率(RR=1.50,95%CI:1.38-1.64)、ALT复常率(RR=1.10,95%CI:1.05-1.16)、HBeAg转阴率(RR=1.23,95%CI:1.08-1.40)和HBeAg血清转...     

Efficacy of sound therapy interventions for tinnitus management: A protocol for systematic review and network meta-analysis

Background:Tinnitus is a common otological symptom and can be debilitating. Sound therapy has increased in popularity due to its potential for increased efficacy and fewer and milder side effects, but the available evidence is limited by the lack of randomized controlled trials comparing different sound therapies for tinnitus. Network meta-analysis (NMA) is a useful tool to compare multiple treatments when there is limited or no direct evidence available. The aim of this paper is to evaluate the efficacy and acceptability of different sound therapies for tinnitus.Methods and analysis:A literature search was conducted to identify articles in EMBASE, PubMed/MEDLINE, Web of Science, Cochrane Library, China National Knowledge Infrastructure, Chinese Biomedical Literature, and Wanfang and Weipu from inception to April 1, 2021. The Tinnitus Handicap Inventory, Tinnitus Questionnaire, and effective rate were used to assess perceived tinnitus suppression after treatment. We used Review Manager 5.4 for the standard meta-analysis; R 4.0.4 and Stata 15.1 were used for the NMA and the publication bias and sensitivity analyses.Results:The effect estimates of the direct comparisons (when available) were very similar to those of the NMA. Overall, sound stimulation alone performed better than medication alone, educational consultation alone, and no treatment. Combination therapy, such as sound stimulation plus educational consultation and sound stimulation plus drug therapy, yielded significantly better outcomes with regard to the alleviation of tinnitus than individual treatments.Conclusion:This is the first NMA to evaluate and compare the effectiveness of different sound therapies for the management of tinnitus. It may help inform the selection of sound therapy and the development of guidelines in clinical practice. Future studies of sound therapy with larger sample sizes involving multiple medical centers are needed to improve the current evidence.     

Treatment of children with HBeAg-positive chronic hepatitis B: A systematic review and meta-analysis

BackgroundEffective management of children with chronic hepatitis B is still an unresolved issue.AimTo assess the outcome of different therapeutic regimens among children with HBeAg-positive chronic hepatitis B.MethodsElectronic database searches identified clinical trials that completed specific periods of treatment and follow-up. Sustained response rates were defined by the loss of HBV DNA and HBeAg, and by the normalization of liver enzymes. The loss of HBsAg and seroconversion to anti-HBs were also listed.ResultsOur searches found 20 eligible articles (1112 enrolled patients, 2–18 years old). Interferon-alpha therapy showed significantly higher sustained response rate and loss of HBsAg than no therapy (Odd's ratio 3.0, 95% confidence interval 1.6–5.4; and 2.3, 1.1–11.3, respectively). The sustained response rate was not significantly different between interferon and interferon plus lamivudine, or plus prednisone, or plus hepatitis B vaccine; this rate was significantly higher for interferon compared with combined interferon plus levamisole or vitamin E.ConclusionInterferon-alpha is still the most effective treatment option for children with HBeAg-positive chronic hepatitis B. Randomized trials are warranted for further comparing interferon to newer antiviral agents in terms of efficacy, safety, emergence of mutant variants, and cost/benefit ratio.     

Efficacy and safety of Chinese herbal for carotid atherosclerosis: A protocol for systematic review and network meta-analysis

Background:Carotid atherosclerosis (CAS) can cause acute events such as myocardial infarction and stroke, seriously injuring human health. There are some shortcomings for statins and surgical in the treatment of CAS. Research has proved that Chinese herbal shows its unique advantages with the multichannel and multitarget treatment strategy. As a result, we propose this study to evaluate the efficacy and safety of Chinese herbal in the treatment of CAS.Method:We will retrieve the relevant databases to collect the studies of Chinese herbal treatment of CAS up to July 2021. The retrieval language is limited to Chinese and English. Researchers will be responsible for screening studies and extracting data, and use STATA16.0 and WinBUGS1.4.3 for data analysis. We will conduct a bias risk assessment based on the Cochrane Collaboration''s bias risk assessment tool and use the grading of recommendations assessment development and evaluation tool to assess the confidence of cumulative evidence.Results:The study will evaluate the efficacy and safety of Chinese herbal in the treatment of carotid atherosclerosis.Conclusion:The study will offer more evidence for the treatment of CAS with Chinese herbal and expand the selection range of clinicians.Protocol registration number:INPLASY2021100112.     

Patient adherence to antiviral treatment for chronic hepatitis B and C: a systematic review

Introduction. Poor adherence to treatment for various chronic diseases is a frequent phenomenon. Current guidelines for the treatment of chronic hepatitis B (HBV) and hepatitis C (HCV) recommend optimal adherence, since it has been suggested that poor adherence is associated with an increased risk of virological failure. We aimed to give an overview of studies exploring adherence to combination treatment (PEG-interferon plus ribavirin) for HCV and nucleos(t)ide analogues for HBV.Material and methods. A systematic review was conducted using the databases PubMed, Embase, Cochrane Library and Web of Knowledge. Search terms included “adherence” or “compliance” combined with “hepatitis B”, “hepatitis C” or “viral hepatitis”.Results. The final selection included 19 studies (13 HCV, 6 HBV). Large differences in patient numbers and adherence assessment methods were found between the various studies. For HCV mean adherence varied from 27 to 97%, whereas the proportion of patients with ≥ 80% adherence varied from 27 to 96%. Mean adherence reported in HBV studies ranged from 81 to 99%, with 66 to 92% of patients being 100% adherent. For both HCV and HBV studies, the highest adherence rates were reported in studies using self-report whereas lower adherence rates were reported in studies using pharmacy claims. Poor adherence to treatment was associated with an increased risk of virological failure.Conclusion. Non-adherence to treatment in chronic viral hepatitis is not a frequent phenomenon. However, given the increased risk of virological failure in poorly adherent patients, clinicians should routinely address adherence issues in all patients treated for chronic viral hepatitis.     

Efficacy of acupuncture for melasma: A protocol of systematic review and meta-analysis

Background:Melasma is a common acquired hyperpigmentation of the skin. The clinical manifestations are light brown or dark brown patches symmetrically distributed on the cheeks, forehead, and mandibular with different shades and unclear borders. The treatment of melasma is extremely challenging due to its easy relapse and hard to cure. As a classical method of traditional Chinese medicine, acupuncture has been used to treat melasma in clinical practice. However, there is no systematic review and meta-analysis of acupuncture on melasma. This study aims to assess the efficacy of acupuncture for melasma.Methods:We will perform a comprehensive retrieval in the following electronic databases: PubMed, EMBASE, the Cochrane Central Register of Controlled Trials, China National Knowledge Infrastructure (CNKI), Wan Fang Database, VIP database, Chinese Biomedical Literature Service System (SinoMed), Chinese Biomedicine (CBM) database, and TCM Literature Analysis from inception to July 1, 2021, to identify any eligible study. We include all randomized controlled trials (RCTs) without any limitation of blinding or publication language, and exclude cohort studies and case reports. The meta-analyses will be conducted by using the Stata16. We will use the Cochrane risk of bias tool for randomized trials to assess the risk of bias of included studies. The X² and I² tests will be utilized to assess the statistical heterogeneity of evidence. We will conduct a meta-analysis if the studies can be combined. Otherwise, a narrative synthesis will be performed. Article screening and data extraction will be independently evaluated by 2 reviewers trained in methodology according to the established selection criteria. Any disagreements between the 2 reviewers will be resolved by reaching a consensus with the other authors (the third reviewer).Results:This study will systematically evaluate the clinical efficacy of acupuncture for melasma.Conclusion:The conclusion of this study will provide evidence to ensure the efficacy of acupuncture for melasma, so as to provide an objective and scientific basis for clinical practice.Ethics and dissemination:No ethical approval will be required because the data used are not linked to individual patient. The results of this review will be published in a peer-reviewed journal.Registration number:INPLASY2021110097.     

Efficacy of pancreatoscopy for pancreatic duct stones: A systematic review and meta-analysis

BACKGROUND Pancreatic duct stones can lead to significant abdominal pain for patients. Per oral pancreatoscopy(POP)-guided intracorporal lithotripsy is being increasingly used for the management of main pancreatic duct calculi(PDC) in chronic pancreatitis. POP uses two techniques: Electrohydraulic lithotripsy(EHL) and laser lithotripsy(LL). Data on the safety and efficacy are limited for this procedure. We performed a systematic review and meta-analysis with a primary aim to calculate the pooled technical and clinical success rates of POP. The secondary aim was to assess pooled rates of technical success, clinical success for the two individual techniques, and adverse event rates.AIM To perform a systematic review and meta-analysis of POP, EHL and LL for management of PDC in chronic pancreatitis.METHODS We conducted a comprehensive search of multiple electronic databases and conference proceedings including PubMed, EMBASE, Cochrane, Google Scholar and Web of Science databases(from 1999 to October 2019) to identify studies with patient age greater than 17 and any gender that reported on outcomes of POP, EHL and LL. The primary outcome assessed involved the pooled technical success and clinical success rate of POP. The secondary outcome included the pooled technical success and clinical success rate for EHL and LL. We also assessed the pooled rate of adverse events for POP, EHL and LL including a subgroup analysis for the rate of adverse event subtypes for POP: Hemorrhage, post-endoscopic retrograde cholangiopancreatography pancreatitis(PEP), perforation, abdominal pain, fever and infections. Technical success was defined as the rate of clearing pancreatic duct stones and clinical success as the improvement in pain. Randomeffects model was used for analysis. Heterogeneity between study-specific estimates was calculated using the Cochran Q statistical test and I~2 statistics. Publication bias was ascertained, qualitatively by visual inspection of funnel plot and quantitatively by the Egger test.RESULTS A total of 16 studies including 383 patients met the inclusion criteria. The technical success rate of POP was 76.4%(95%CI: 65.9-84.5; I~2 = 64%) and clinical success rate was 76.8%(95%CI: 65.2-85.4; I~2 = 66%). The technical success rate of EHL was 70.3%(95%CI: 57.8-80.3; I~2 = 36%) and clinical success rate of EHL was 66.5%(95%CI: 55.2-76.2; I~2 = 19%). The technical success rate of LL was 89.3%(95%CI: 70.5-96.7; I~2 = 70%) and clinical success rate of LL was 88.2%(95%CI: 66.4-96.6; I~2 = 77%). The incidence of pooled adverse events for POP was 14.9%(95%CI: 9.2-23.2; I~2 = 49%), for EHL was 11.2%(95%CI: 5.9-20.3; I~2 = 15%) and for LL was 13.1%(95%CI: 6.3-25.4; I~2 = 31%). Subgroup analysis of adverse events showed rates of PEP at 7%(95%CI: 3.5-13.6; I~2 = 38%), fever at 3.7%(95%CI: 2-6.9; I~2 = 0), abdominal pain at 4.7%(95%CI: 2.7-7.8; I~2 = 0), perforation at 4.3%(95%CI: 2.1-8.4; I~2 = 0), hemorrhage at 3.4%(95%CI: 1.7-6.6; I~2 = 0) and no mortality. There was evidence of publication bias based on funnel plot analysis and Egger's test.CONCLUSION Our study highlights the high technical and clinical success rates for POP, EHL and LL. POP-guided lithotripsy could be a viable option for management of chronic pancreatitis with PDC.     

乙酰左卡尼汀治疗成人糖尿病周围神经病变的有效性:系统评价和网状Meta分析

目的应用网状Meta分析,比较乙酰左卡尼汀(ALC)与其他常用口服药物治疗糖尿病周围神经病变(DPN)患者的疗效。方法检索中英文电子数据库从建库至2020年2月的文献,纳入包含以下1种或多种药物,包括ALC、α-硫辛酸(ALA)、依帕司他、甲钴胺、胰激肽原酶(口服单药疗法),治疗成人DPN的已发表随机对照试验(RCT)。以神经传导速度(NCV)为主要结局指标,次要结局指标包括波幅、神经症状和体征、疼痛等。采用贝叶斯方法(随机效应模型)对纳入的研究进行网状Meta分析,同时估计各个药物疗效的排序概率,计算其累积排序概率图下面积(SUCRA)。结果最终55项RCT纳入网状Meta分析,包括6473例患者。所有纳入研究均含2个对比组,包括4种治疗药物(ALC、ALA、依帕司他、甲钴胺),其中,涉及ALC的研究为3项(2项对比安慰剂、1项对比甲钴胺)。与甲钴胺相比,ALC可改善正中感觉神经NCV[MD为4.0(95%CI为0.1~7.9)m/s];而在其他神经相关的NCV改善上,尽管从排序结果看,相对于其他常用口服阳性药物,ALC可能在改善正中感觉神经(SUCRA为91.6%)、尺运动神经(SUCRA为69.3%)和尺感觉神经(SUCRA为77.8%)NCV更优;但相对效应值并未发现ALC与其他药物单药治疗有明显差异。结论在DPN治疗中,ALC可能具有改善感觉神经和疼痛的疗效优势,在其他结局上与其他常用口服药物疗效相似。     

Efficacy of acupuncture for whiplash injury: A protocol for systematic review and meta-analysis

Background:Studies in both Eastern & Western countries such as the United States and Europe have evaluated the efficacy of acupuncture for whiplash injury or whiplash-associated disorder (WAD). However, no systematic reviews on the effectiveness of acupuncture on WAD have been conducted since 2014. Therefore, we are planning an updated systematic review of studies published since 2014 to overcome the limitations of existing evidence.Methods:Literature will be identified from searches of relevant databases, including international databases such as PubMed, Ovid-Medline, Embase, The Cochrane Library, and China National Knowledge Infrastructure and Korean databases such as Korea Med, Korean Studies Information Service System, Oriental Medicine Advanced Searching Integrated System, and National Digital Science Library. Only randomized controlled trials using acupuncture or electro-acupuncture for whiplash injury will be included. The primary outcomes will be the visual analog scale or numerical rating scale of the neck pain, while the secondary outcome is the range of motion of the neck. The risk of bias for individual papers will be assessed by two independent investigators using the Cochrane “Risk of Bias” assessment tool.Dissemination:We plan to report the results of the study in a peer-reviewed journal after completing the research. In addition, we expect this study to provide invaluable information to clinicians treating patients with WAD with acupuncture or electro-acupuncture.Trial registration number:PROSPERO 2021: CRD42021261595. Registered on 18 July 2021. https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=261595