Effect of Extracorporeal Blood Purification on Mortality in Sepsis: A Meta-Analysis and Trial Sequential Analysis

Objective: The objective of this study was to conduct a meta-analysis and trial sequential analysis (TSA) of published randomized controlled trials (RCTs) to determine whether mortality benefit exists for extracorporeal blood purification techniques in sepsis. Data Sources: A systematic search on MEDLINE, Embase, and the Cochrane Central Register of Controlled Trials for RCTs was performed. Study Selection: RCTs investigating the effect of extracorporeal blood purification device use on mortality among critically ill septic patients were selected. Data Extraction: Mortality was assessed using Mantel-Haenszel models, and I2 was used for heterogeneity. Data are presented as odds ratios (OR); 95% confidence intervals (CIs); p values; I2. Using the control event mortality proportion, we performed a TSA and calculated the required information size using an anticipated intervention effect of a 14% relative reduction in mortality. Data Synthesis: Thirty-nine RCTs were identified, with 2,729 patients. Fourteen studies used hemofiltration (n = 789), 17 used endotoxin adsorption devices (n = 1,363), 3 used nonspecific adsorption (n = 110), 2 were cytokine removal devices (n = 117), 2 used coupled plasma filtration adsorption (CPFA) (n = 207), 2 combined hemofiltration and perfusion (n = 40), and 1 used plasma exchange (n = 106). On conventional meta-analysis, hemofiltration (OR 0.56 [0.40–0.79]; p < 0.001; I2 = 0%), endotoxin removal devices (OR 0.40 [0.23–0.67], p < 0.001; I2 = 71%), and nonspecific adsorption devices (OR 0.32 [0.13–0.82]; p = 0.02; I2 = 23%) were associated with mortality benefit, but not cytokine removal (OR 0.99 [0.07–13.42], p = 0.99; I2 = 64%), CPFA (OR 0.50 [0.10–2.47]; p = 0.40; I2 = 64%), or combined hemofiltration and adsorption (OR 0.71 [0.13–3.79]; p = 0.69; I2 = 0%). TSA however revealed that based on the number of existing patients recruited for RCTs, neither hemofiltration (TSA-adjusted CI 0.29–1.10), endotoxin removal devices (CI 0.05–3.40), nor nonspecific adsorption devices (CI 0.01–14.31) were associated with mortality benefit. Conclusion: There are inadequate data at present to conclude that the use of extracorporeal blood purification techniques in sepsis is beneficial. Further adequately powered RCTs are required to confirm any potential mortality benefit, which may be most evident in patients at greatest risk of death.

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Traction Therapy for Cervical Radicular Syndrome is Statistically Significant but not Clinically Relevant for Pain Relief. A Systematic Literature Review with Meta-Analysis and Trial Sequential Analysis

Journal of Clinical Medicine ◽

10.3390/jcm9113389 ◽

2020 ◽

Vol 9 (11) ◽

pp. 3389

Author(s):

Claudio Colombo ◽

Stefano Salvioli ◽

Silvia Gianola ◽

Greta Castellini ◽

Marco Testa

Keyword(s):

Sequential Analysis ◽

Meta Analysis ◽

Risk Of Bias ◽

Treatment Modalities ◽

Trial Sequential Analysis ◽

Controlled Trials ◽

Cochrane Central Register ◽

Quality Of Evidence ◽

Radicular Syndrome

Aim: We aimed to investigate the effectiveness of traction therapy in reducing pain by performing a systematic review with meta-analysis. We also explore the best modality for administering traction to patients with cervical radicular syndrome (CRS). Methods: We searched the Medline, Physiotherapy Evidence Database (PEDro), Cochrane Central Register of Controlled Trials, and Cumulative Index to Nursing and Allied Health Literature (CINAHL) electronic databases. Two reviewers independently selected randomized controlled trials (RCTs) that compared traction in addition to other treatments versus the effectiveness of other treatments alone for pain outcome. We calculated the mean differences (MDs) and 95% confidence intervals (CIs). We used Cochrane’s tool to assess risk of bias and the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system to evaluate the quality of evidence and summarize the study conclusions. Results: A total of seven studies (589 patients), one with low risk of bias, were evaluated. An overall estimate of treatment modalities showed low evidence that adding traction to other treatments is statistically significant (MD −5.93 [95% CI, −11.81 to −0.04] P = 0.05 and I2 = 57%) compared to other treatments alone. The subgroup analyses were still statistically significant only for mechanical and continuous modalities. Conclusions: Overall analysis showed that, compared to controls, reduction in pain intensity after traction therapy was achieved in patients with cervical radiculopathy. However, the quality of evidence was generally low and none of these effects were clinically meaningful.

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Ganglioside-monosialic acid (GM1) for prevention of chemotherapy-induced peripheral neuropathy: a meta-analysis with trial sequential analysis

10.21203/rs.3.rs-431559/v1 ◽

2021 ◽

Author(s):

Shaoyong Wu ◽

Xiaohui Bai ◽

Caixia Guo ◽

Zhimei Huang ◽

Handong Ouyang ◽

...

Keyword(s):

Peripheral Neuropathy ◽

Adverse Events ◽

Sequential Analysis ◽

Meta Analysis ◽

Trial Sequential Analysis ◽

Controlled Trials ◽

Cochrane Central Register ◽

Random Errors ◽

Clinical Issue ◽

Response To Chemotherapy

Abstract Background: Chemotherapy-induced peripheral neuropathy (CIPN) is a dose-limiting side effect that largely remains an unresolved clinical issue, leading to long-term morbidity. This meta-analysis aimed to evaluate the efficacy and safety of Ganglioside-monosialic acid (GM1) in preventing CIPN.Methods: Systematic literature searches of Embase, Web of Science, the Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov were performed to identify randomized controlled trials and cohort studies that evaluated the efficacy of GM1 for preventing CIPN. Ameta-analysis was conducted to calculate odds ratios (ORs) and 95% confidential intervals (CIs) using a random-effects model. Trial sequential analyses (TSA) also were conducted to control for random errors. Results: A total of five studies involving 868 participants were included. The results showed that GM1 did not reduce the overall incidence of grade ≥2 CIPN when the common terminology criteria for adverse events (CTCAE) was used (OR 0.34, 95% CI 0.34-1.11). Subgroup analyses showed that GM1 could not reduce the risk of CTCAE grade ≥2 CIPN (OR 0.63, 95% CI 0.35-1.13) and neurotoxicity criteria of Debiopharm (DEB-NTC) grade ≥2 CIPN (OR 0.25, 95% CI 0.01-7.10) in oxaliplatin-treated patients, although GM1 might reduce the risk of CTCAE grade≥2 CIPN in the taxane subgroup in one study (OR 0.003, 95% CI 0.00-0.05). Besides, TSA suggested that the results in the taxane subgroup were robust, while that of the oxaliplatin subgroup were inconclusive. Furthermore, GM1 did not influence the rate of response to chemotherapy and CTCAE grade ≥2 adverse events such as fatigue, nausea, diarrhea, and rash.Conclusions: GM1 was not associated with a lower risk of oxaliplatin-induced peripheral neuropathy nor could improve the response or safety to chemotherapy; however, it might be able to prevent taxane-induced peripheral neuropathy. Higher-quality trials are required to clarify the preventive effect of GM1 in oxaliplatin-treated patients.

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Exploring the appropriate dose of nebulized hypertonic saline for bronchiolitis: a dose–response meta-analysis

Journal of Investigative Medicine ◽

10.1136/jim-2021-001947 ◽

2021 ◽

pp. jim-2021-001947

Author(s):

Jilei Lin ◽

Yin Zhang ◽

Anchao Song ◽

Linyan Ying ◽

Jihong Dai

Keyword(s):

Hypertonic Saline ◽

Dose Response ◽

Sequential Analysis ◽

Meta Analysis ◽

Trial Sequential Analysis ◽

Controlled Trials ◽

Cochrane Central Register ◽

Eligibility Criteria ◽

Significant Difference ◽

Different Doses

Nebulized hypertonic saline (HS) has gathered increasing attention in bronchiolitis. This study aims to evaluate the relationship between the dose of nebulized HS and the effects on bronchiolitis. Five electronic databases—PubMed, EMBASE, Cochrane Central Register of Controlled Trials, ClinicalTrials.gov, and ISRCTN—were searched until May 2021. Randomized controlled trials (RCTs) that investigated the effect of HS on bronchiolitis were included. A total of 35 RCTs met the eligibility criteria. HS nebulization may shorten the length of stay (LOS) in hospital (mean difference −0.47, 95% CI −0.71 to –0.23) and improve the 24-hour, 48-hour, and 72-hour Clinical Severe Score (CSS) in children with bronchiolitis. The results showed that there was no significant difference between 3% HS and the higher doses (>3%) of HS in LOS and 24-hour CSS. Although the dose–response meta-analysis found that there may be a linear relationship between different doses and effects, the slope of the linear model changed with different included studies. Besides, HS nebulization could reduce the rate of hospitalization of children with bronchiolitis (risk ratio 0.88, 95% CI 0.78 to 0.98), while the trial sequential analysis indicated the evidence may be insufficient and potentially false positive. This study showed that nebulized HS is an effective and safe therapy for bronchiolitis. More studies are necessary to be conducted to evaluate the effects of different doses of HS on bronchiolitis.

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Ganglioside-monosialic acid (GM1) for prevention of chemotherapy-induced peripheral neuropathy: a meta-analysis with trial sequential analysis

BMC Cancer ◽

10.1186/s12885-021-08884-4 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Shaoyong Wu ◽

Xiaohui Bai ◽

Caixia Guo ◽

Zhimei Huang ◽

Handong Ouyang ◽

...

Keyword(s):

Peripheral Neuropathy ◽

Adverse Events ◽

Randomized Controlled Trials ◽

Sequential Analysis ◽

Meta Analysis ◽

Trial Sequential Analysis ◽

Controlled Trials ◽

Cochrane Central Register ◽

Clinical Issue ◽

Randomized Controlled

Abstract Background Chemotherapy-induced peripheral neuropathy (CIPN) is a dose-limiting side effect that largely remains an unresolved clinical issue, leading to long-term morbidity. This meta-analysis aimed to evaluate the efficacy and safety of Ganglioside-monosialic acid (GM1) in preventing CIPN. Methods Systematic literature searches of PubMed, Web of Science, Embase, the Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov were performed to identify randomized controlled trials and cohort studies that evaluated the efficacy of GM1 for preventing CIPN. Conventional meta-analysis with a random-effects model and trial sequential analysis (TSA) were performed. Results A total of five studies involving 868 participants were included. The results showed that GM1 did not reduce the overall incidence of grade ≥ 2 CIPN when the common terminology criteria for adverse events (CTCAE) was used (OR 0.34, 95% CI 0.34–1.11). Subgroup analyses showed that GM1 could not reduce the risk of CTCAE grade ≥ 2 CIPN (OR 0.63, 95% CI 0.35–1.13) and neurotoxicity criteria of Debiopharm (DEB-NTC) grade ≥ 2 CIPN (OR 0.25, 95% CI 0.01–7.10) in oxaliplatin-treated patients, despite that GM1 was associated with a reduced risk of CTCAE grade ≥ 2 CIPN in the taxane subgroup of one study (OR 0.003, 95% CI 0.00–0.05). These results were confirmed by the sub-analysis of randomized controlled trials (RCTs). In TSA, the z-curve for the taxane subgroup crossed the upper trial sequential monitoring boundary (TSMB) but do not reach the required information size (RIS). The z-curves for the oxaliplatin subgroup remained in the nonsignificant area and did not reach the RIS. Further, GM1 did not influence the rate of response to chemotherapy and CTCAE grade ≥ 2 adverse events such as fatigue, nausea, diarrhea, and rash. Conclusions GM1 seemed to be well-tolerated and did not influence the anti-cancer effects of chemotherapeutic agents. Although the data did not confirm the effectiveness of GM1 in preventing oxaliplatin-induced peripheral neuropathy, GM1 might be able to prevent taxane-induced peripheral neuropathy. More studies are required in different ethnic populations receiving taxane-based chemotherapy to confirm these findings.

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Acupuncture for breathlessness in advanced cancer: a protocol for systematic review and meta-analysis with trial sequential analysis

BMJ Open ◽

10.1136/bmjopen-2021-054917 ◽

2021 ◽

Vol 11 (11) ◽

pp. e054917

Author(s):

Zihan Yin ◽

Tao Xu ◽

Mingsheng Sun ◽

Ling Zhao ◽

Fanrong Liang

Keyword(s):

Systematic Review ◽

Advanced Cancer ◽

Sequential Analysis ◽

Meta Analysis ◽

Biomedical Literature ◽

Cochrane Library ◽

Trial Sequential Analysis ◽

Controlled Trials ◽

Cochrane Central Register

IntroductionBreathlessness in advanced cancer, a frequent multicomponent and debilitating disorder, severely reduces function and quality of patients’ life. Multiple studies have shown that non-pharmacological therapies can effectively palliate breathlessness in advanced cancer. However, no systematic review has investigated the application of acupuncture, as a non-pharmacological treatment, for breathlessness in advanced cancer. A systematic review will be conducted to summarise evidence supporting the efficacy and safety of acupuncture as a therapeutic option for breathlessness in advanced cancer based on existing randomised controlled trials (RCTs).MethodsRCTs will be retrieved from nine scientific databases, including the MEDLINE via PubMed, Web of Science via the Web of Knowledge, Embase via Ovid, the Cochrane Central Register of Controlled Trials via the Cochrane Library, and Allied and Complementary Medicine Database via EBSCO, China National Knowledge Infrastructure, Wanfang Database, VIP Database, Chinese Biomedical Literature Database; three clinical registry platforms, including the WHO International Clinical Trials Registry Platform, NIH Clinical trials.gov and Chinese Clinical Trial Registry, as well as from other sources. Studies published since inception of these databases to 1 August 2021 will be retrieved. Search terms will include breathlessness, cancer, acupuncture and RCT. Two investigators will independently select and extract data from RCTs and assess the risk of bias. The primary outcome, which is alleviation of breathlessness, will be assessed. Meta-analysis will be performed using RevMan V.5.4 and STATA V.15.0. The TSA 0.9.5.10 β software will be used to conduct trial sequential analysis. Finally, the quality of evidence from RCTs will be assessed using the Grading of Recommendations Assessment, Development and Evaluation System tool.Ethics and disseminationResults will be disseminated through peer-reviewed journals or conference reports. Since this study involves acquisition of secondary data, ethical approval requirements will be waived.PROSPERO registration numberCRD42021240085.

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Safety and Efficacy of Roxadustat for Anemia in Patients With Chronic Kidney Disease: A Meta-Analysis and Trial Sequential Analysis

Frontiers in Medicine ◽

10.3389/fmed.2021.724456 ◽

2021 ◽

Vol 8 ◽

Author(s):

Chao Liu ◽

Zhangning Fu ◽

Jiawei Jiang ◽

Kun Chi ◽

Xiaodong Geng ◽

...

Keyword(s):

Chronic Kidney Disease ◽

Kidney Disease ◽

Iron Metabolism ◽

Sequential Analysis ◽

Meta Analysis ◽

Hypoxia Inducible Factor ◽

Trial Sequential Analysis ◽

Controlled Trials ◽

Cochrane Central Register ◽

Safety And Efficacy

Background: Roxadustat, a hypoxia-inducible factor prolyl-hydroxylase inhibitor (HIF-PHI), has been used to treat anemia in patients with chronic kidney disease (CKD). However, its safety and efficacy remain controversial.Methods: The PubMed, EMBASE, Science Citation Index, Cochrane Central Register of Controlled Trials, and Clinical Trial Registries databases were searched for relevant studies published up to April 2021. We identified randomized controlled trials (RCTs) comparing roxadustat with placebo or erythropoiesis-stimulating agents (ESAs) in anemia patients with CKD with or without dialysis.Results: Eleven studies including 6,631 patients met the inclusion criteria. In non-dialysis-dependent (NDD-) and dialysis-dependent (DD-) CKD patients, the total adverse events were not significantly different between the roxadustat and control (placebo for NDD-CKD patients and ESA for DD-CKD patients) groups [relative risk (RR) = 1.02, 95% confidence interval (CI) = 1.00, 1.04, P = 0.08, and RR = 1.22, 95% CI = 0.91, 1.64, P = 0.18, respectively], and the trial sequential analysis (TSA) confirmed the result in the NDD-CKD groups. No significant differences in hyperkalemia and infection incidences were found between roxadustat and placebo in the DD-CKD groups. The pooled results showed that roxadustat significantly increased the hemoglobin response rate compared with placebo in the NDD-CKD group and had an effect similar to that of ESA in the DD-CKD group. However, iron metabolism parameters did not seem to be obviously optimized by roxadustat.Conclusion: Roxadustat can be safely used in CKD patients. Oral roxadustat was more effective than placebo as a therapy for anemia in NDD-CKD patients and non-inferior to ESA in correcting anemia in DD-CKD patients. However, additional clinical trials are still needed to further prove whether roxadustat can optimize iron metabolism.

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