Traditional Pairwise Meta-analysis Research Articles

EBNEO Commentary: A network meta-analysis of postnatal corticosteroids for bronchopulmonary dysplasia: Has the most appropriate treatment been revealed?

Ramaswamy VV, Bandyopadhyay T, Nanda D, Bandiya P, Ahmed J, Garg A, Roehr CC, Nangia S. Assessment of Postnatal Corticosteroids for the Prevention of Bronchopulmonary Dysplasia in Preterm Neonates: A Systematic Review and Network Meta-analysis. JAMA Pediatr 2021; 175(6): e206826. PMID 33720274. Systemic postnatal corticosteroids (PNCs) reduce the risk of bronchopulmonary dysplasia (BPD) in preterm infants but may contribute to long-term neurodevelopmental harm. The need to identify a treatment regimen with a reassuring risk-benefit balance remains.1 In an extraordinary feat of data aggregation, Ramaswamy and colleagues include 62 randomised clinical trials (RCTs) enrolling 5559 neonates in a systematic review and network meta-analysis (NMA) to determine which of 14 distinct PNC exposures (Table) may be most appropriate.2 The authors suggest moderately early-initiated medium cumulative dose systemic dexamethasone is the best regimen. Unlike traditional pairwise meta-analyses, NMAs compare multiple interventions, adding relevance to clinical scenarios with various alternative treatment options. NMAs also allow indirect comparisons between interventions, linking them through a common comparator.3 For example, no RCTs have compared early systemic hydrocortisone (EHC) to late-initiated low-cumulative dose systemic dexamethasone (LaLdDx), but a shared comparison to placebo in separate RCTs allows a relative risk estimation. The validity of NMA results relies on specific assumptions. A critical one is that the data linked to produce indirect evidence display ‘transitivity’.3 In essence, that aggregation may be justified by similarities in key population characteristics. Tools that guide this subjective judgement include assessment of whether the populations are similar on important effect modifiers and whether the indirect comparisons could be assessed in head-to-head trials. Extending the example above, we consider the tools against the PREMILOC (EHC) and DART (LaLdDx) trials.4, 5 A meta-regression identified the baseline risk of developing BPD as an important effect modifier for the effect of PNCs on death or cerebral palsy.6 The rates of death or BPD in the control groups of PREMILOC and DART were 49% and 91%, respectively, questioning their similarity.4, 5 In turn, a hypothetical trial of EHC versus LaLdDx would presumably compare prophylactic EHC to LaLdDx only amongst infants remaining on mechanical ventilation at 14 days. Exposing subjects to LaLdDx irrespective of respiratory status would raise ethical concerns. However, the indirect comparison generated by the NMA is not of prophylactic EHC versus expectant management with rescue LaLdDx. Though we focus on EHC versus LaLdDx as an example, these concerns extend to various comparisons. One could argue that transitivity is generally violated when comparing interventions applied in distinct stages of disease progression, and that use of PNCs as prophylaxis versus treatment of evolving severe BPD are distinct indications best suited to distinct comparisons.3 Lastly, we should avoid labelling the PNC regimen most effective against BPD as ‘most appropriate’. Although a reduction in BPD with various PNC regimens is probable, the avoidance of risk for adverse long-term neurodevelopmental outcomes is uncertain, and the latter will guide appropriateness. Further, as the authors acknowledge, the quality of evidence supporting the conclusion is low. Despite these points of caution, Ramaswamy and colleagues add a rich contribution to the literature, shining a helpful light on the path forward. Conclusively arriving at best practice will require additional high-quality research, followed by cautious data synthesis that prioritises long-term outcomes of importance to patients and their families. URL: https://ebneo.org/postnatal-corticosteroids-meta-analysis. None.

Role of maintenance strategies in advanced epithelial ovarian cancer: a systematic review, network meta-analysis and cost-effectiveness analysis protocol

IntroductionDifferent maintenance strategies have shown efficacy in patients with advanced ovarian cancer, but without drawing any conclusion on which strategy is preferred. Therefore, we will conduct a network meta-analysis and...

The effect of prophylactic balloon occlusion in patients with placenta accreta spectrum: a Bayesian network meta-analysis.

Placenta accreta spectrum (PAS) can induce severe life-threatening obstetric hemorrhage. Herein, we conducted a Bayesian network meta-analysis of previous studies to evaluate the relative benefits of different prophylactic balloon occlusion (PBO) procedures. PubMed, Embase, Cochrane Library, and Web of Science were searched from inception to July 2021. Blood loss volume, blood transfusion volume, and hysterectomy rate were regarded as the primary endpoints. The data were pooled using a Bayesian network and traditional pairwise meta-analysis. Fifty-nine articles with a total sample size of 5150 patients were included. Compared with no PBO (non-PBO) intervention, PBO of the abdominal aorta (PBOAA, mean difference(MD) - 1.02, 95% credible interval (CrI) - 1.4 to - 0.67), common iliac artery (PBOCIA, MD - 0.84; 95%CrI - 1.36 to - 0.06) and internal iliac artery (PBOIIA, MD - 0.42; 95%CrI - 0.72 to - 0.13) significantly lowered blood loss volume, with PBOAA being more effective than PBOIIA (MD - 0.60; 95%CrI - 1.05 to - 0.17). PBOAA and PBOIIA also significantly decreased blood loss volume (MD - 2.33; 95%CrI - 3.74 to - 0.94, MD - 1.57; 95%CrI - 2.77 to - 0.47 respectively) and hysterectomy rate (OR 0.31; 95%CrI 0.16 to 0.54, OR 0.53; 95%CrI 0.29 to 0.92 respectively). PBOAA has the highest probability of being more effective in reducing the blood loss volume, blood transfusion volume, and hysterectomy rate. Performing PBOAA, PBOCIA, or PBOIIA in PAS patients is an effective way to minimize blood loss volume, while PBOAA and PBOIIA also reduce blood transfusion volume and hysterectomy rate. PBOAA is a notably more effective strategy to reduce blood loss volume than PBOIIA. • PBOAA, PBOCIA, and PBOIIA procedures can significantly reduce the blood loss volume compared to non-PBO intervention in PAS patients, of which PBOAA was more effective than the PBOIIA procedure. • PBOAA and PBOIIA could significantly reduce the blood transfusion volume and hysterectomy rate in contrast to the non-PBO intervention in patients with PAS. • According to our statistical treatment ranking, PBOAA was statistically superior in reducing blood transfusion volume, blood transfusion volume, and hysterectomy rate than other PBO procedures.

Comparison of Five Prophylactically Intravenous Drugs in Preventing Opioid-Induced Cough: A Bayesian Network Meta-Analysis of Randomized Controlled Trials.

Background: Due to the absence of direct comparisons of different therapeutic drugs in preventing opioid-induced cough (OIC) during the induction of general anesthesia, clinicians often faced difficulties in choosing the optimal drug for these patients. Hence, this network meta-analysis was conducted to solve this problem. Methods: Online databases, including Pubmed, Embase, Web of Science, Cochrane, and Google Scholar, were searched comprehensively to identify eligible randomized controlled trials (RCTs), up to March 15th, 2021. Within a Bayesian framework, network meta-analysis was performed by the “gemtc” version 0.8.2 package of R-3.4.0 software, and a pooled risk ratio (RR) associated with 95% credible interval (CrI) was calculated. Results: A total of 20 RCTs were finally enrolled, and the overall heterogeneity for this study was low to moderate. Traditional pair-wise meta-analysis results indicated that all of the five drugs, namely, lidocaine, ketamine, dezocine, butorphanol, and dexmedetomidine could prevent OIC for four clinical outcomes, compared with the placebo (all p-values < 0.05). Moreover, dezocine had the best effect, compared with that of the other drugs (all p-values < 0.05). Network meta-analysis results suggested that the top three rank probabilities for four clinical outcomes from best to worst were dezocine, butorphanol, and ketamine based on individual/cumulative rank plots and surface under the cumulative ranking curve (SUCRA) probabilities. The node-splitting method indicated the consistency of the direct and indirect evidence. Conclusions: Our results indicated that all of these five drugs could prevent OIC compared with the placebo. Moreover, the top three rank probabilities for four clinical outcomes from best to worst were dezocine, butorphanol, and ketamine. Our results were anticipated to provide references for guiding clinical research, and further high-quality RCTs were required to verify our findings. Systematic Review Registration: [https://www.crd.york.ac.uk/prospero/], identifier [CRD42021243358].

Strategies to Prevent Acute Kidney Injury after Pediatric Cardiac Surgery: A Network Meta-Analysis.

AKI is a common complication after pediatric cardiac surgery and has been associated with higher morbidity and mortality. We aimed to compare the efficacy of available pharmacologic and nonpharmacologic strategies to prevent AKI after pediatric cardiac surgery. PubMed/MEDLINE, Embase, Cochrane Controlled Trials Register, and reference lists of relevant articles were searched for randomized controlled trials from inception until August 2020. Random effects traditional pairwise, Bayesian network meta-analyses, and trial sequential analyses were performed. Twenty randomized controlled trials including 2339 patients and 11 preventive strategies met the eligibility criteria. No overall significant differences were observed compared with control for corticosteroids, fenoldopam, hydroxyethyl starch, or remote ischemic preconditioning in traditional pairwise meta-analysis. In contrast, trial sequential analysis suggested a 80% relative risk reduction with dexmedetomidine and evidence of <57% relative risk reduction with remote ischemic preconditioning. Nonetheless, the network meta-analysis was unable to demonstrate any significant differences among the examined treatments, including also acetaminophen, aminophylline, levosimendan, milrinone, and normothermic cardiopulmonary bypass. Surface under the cumulative ranking curve probabilities showed that milrinone (76%) was most likely to result in the lowest risk of AKI, followed by dexmedetomidine (70%), levosimendan (70%), aminophylline (59%), normothermic cardiopulmonary bypass (57%), and remote ischemic preconditioning (55%), although all showing important overlap. Current evidence from randomized controlled trials does not support the efficacy of most strategies to prevent AKI in the pediatric population, apart from limited evidence for dexmedetomidine and remote ischemic preconditioning.

Efficacy of Intrawound Treatments to Prevent Surgical Site Infection after Spine Surgery: A Systematic Review and Network Meta-analysis

Intrawound treatments have been reported to have favorable efficacy for preventing surgical site infection (SSI); however, the best strategy remains unknown. The aim of this systematic review and network meta-analysis was to evaluate the efficacy of intrawound treatments to prevent SSI after spine surgery. A systematic review and network meta-analysis. We searched the Cochrane Library, EMbase, PubMed, Chinese Science and Technology Periodical Database (VIP), China National Knowledge Infrastructure (CNKI), and Wanfang Data from the date of inception to March 2, 2020. The randomized controlled trials (RCTs) and cohort studies were identified and extracted by 2 reviewers independently. We performed a traditional pairwise meta-analysis to evaluate overall efficacy of intrawound treatments. Meanwhile, a network meta-analysis was performed to compare and rank the treatment efficacy using frequentist approach. Thirty-three publications (6 RCTs and 27 retrospective cohort studies) were included, involving 22,763 patients. For pairwise meta-analysis, the combined results showed that the intrawound treatment had a significantly lower SSI rate than the control group (CG) (odds ratio [OR] = 0.41; 95% confidence interval [CI], 0.31-0.55). For network meta-analysis, the treatment of vancomycin (VA) (OR = 0.53; 95% CI, 0.39-0.71), povidone-iodine (PI) (OR = 0.10; 95% CI, 0.04 - 0.23), and vancomycin + povidone-iodine (VA+PI) (OR = 0.25; 95% CI, 0.11-0.58) were found to be significantly more efficacious than CG on reduction of SSI rate. PI ranked first on reducing SSI, followed by PI+HP, VA+PI, gentamicin (GM), VA, and hydrogen peroxide (HP); CG ranked last. Firstly, only 6 RCTs are included in this systematic review. Retrospective cohort studies tend to exaggerate the real results, although most of them are high-quality according to the Newcastle-Ottawa Quality Assessment Scale (NOQAS). More high-quality RCTs need to be included to obtain convincing conclusions. Secondly, the population of this study involves both adult and pediatric cohorts, patients with tumor, congenital disease, or degenerative disease. There is no subgroup analysis for ages and type of diseases, which might have influence on the overall pooled analysis. Thirdly, we define the application of saline solution and no intrawound treatment as the control group, which might ignore their heterogeneity. Fourthly, follow-up periods are variable and the sample size of HP is small. Finally, additional research is needed to compare the complications of different treatments and the benefits of various dosages. We found that VA and PI show promising results on reducing SSI. PI is recommended as the most efficacious intrawound treatment to prevent SSI after spine surgery.

Tuberculosis preventive therapy for people living with HIV: A systematic review and network meta-analysis.

Tuberculosis (TB) preventive therapy (TPT) is an essential component of care for people living with HIV (PLHIV). We compared efficacy, safety, completion, and drug-resistant TB risk for currently recommended TPT regimens through a systematic review and network meta-analysis (NMA) of randomized trials. We searched MEDLINE, Embase, and the Cochrane Library from inception through June 9, 2020 for randomized controlled trials (RCTs) comparing 2 or more TPT regimens (or placebo/no treatment) in PLHIV. Two independent reviewers evaluated eligibility, extracted data, and assessed the risk of bias. We grouped TPT strategies as follows: placebo/no treatment, 6 to 12 months of isoniazid, 24 to 72 months of isoniazid, and rifamycin-containing regimens. A frequentist NMA (using graph theory) was carried out for the outcomes of development of TB disease, all-cause mortality, and grade 3 or worse hepatotoxicity. For other outcomes, graphical descriptions or traditional pairwise meta-analyses were carried out as appropriate. The potential role of confounding variables for TB disease and all-cause mortality was assessed through stratified analyses. A total of 6,466 unique studies were screened, and 157 full texts were assessed for eligibility. Of these, 20 studies (reporting 16 randomized trials) were included. The median sample size was 616 (interquartile range [IQR], 317 to 1,892). Eight were conducted in Africa, 3 in Europe, 3 in the Americas, and 2 included sites in multiple continents. According to the NMA, 6 to 12 months of isoniazid were no more efficacious in preventing microbiologically confirmed TB than rifamycin-containing regimens (incidence rate ratio [IRR] 1.0, 95% CI 0.8 to 1.4, p = 0.8); however, 6 to 12 months of isoniazid were associated with a higher incidence of all-cause mortality (IRR 1.6, 95% CI 1.2 to 2.0, p = 0.02) and a higher risk of grade 3 or higher hepatotoxicity (risk difference [RD] 8.9, 95% CI 2.8 to 14.9, p = 0.004). Finally, shorter regimens were associated with higher completion rates relative to longer regimens, and we did not find statistically significant differences in the risk of drug-resistant TB between regimens. Study limitations include potential confounding due to differences in posttreatment follow-up time and TB incidence in the study setting on the estimates of incidence of TB or all-cause mortality, as well as an underrepresentation of pregnant women and children. Rifamycin-containing regimens appear safer and at least as effective as isoniazid regimens in preventing TB and death and should be considered part of routine care in PLHIV. Knowledge gaps remain as to which specific rifamycin-containing regimen provides the optimal balance of efficacy, completion, and safety.

Comparing Nonoperative Treatment, MPFL Repair, and MPFL Reconstruction for Patients With Patellar Dislocation: A Systematic Review and Network Meta-analysis.

Background:Medial patellofemoral ligament (MPFL) reconstruction, MPFL repair, and nonoperative treatment are important treatments for patients with patellar dislocation. However, it is unclear which treatment leads to better outcomes.Purpose:To determine the efficacy and safety of the 3 treatments in the treatment of patellar dislocation and compare the effect of MPFL reconstruction with MPFL repair, MPFL reconstruction with nonoperative treatment, and MPFL repair with nonoperative treatment.Study Design:Systematic review; Level of evidence, 3.Methods:The PubMed, Web of Science, Cochrane Library, Embase, CNKI (China National Knowledge Infrastructure), and Wanfang databases were searched from inception to December 2020. Included were clinical studies that described the efficacy and safety of 2 of the 3 treatments, studies directly comparing the clinical effects of the 2 operative techniques, or studies comparing the effects of reconstruction or repair with nonoperative treatment. Two reviewers independently extracted data and assessed the quality of the included studies with the Cochrane risk-of-bias tools. The outcomes evaluated were postoperative redislocation rate, revision rate, complications, and Kujala score. We used traditional direct pairwise meta-analysis as well as network meta-analysis for comprehensive efficacy of all 3 treatment measures.Results:Twelve studies were included: 5 compared MPFL reconstruction with MPFL repair, 2 compared MPFL reconstruction with nonoperative treatment, and 5 compared MPFL repair with nonoperative treatment. The risk of bias was serious in 4, moderate in 4 and low in 4 articles. MPFL reconstruction led to significantly reduced redislocation and improved Kujala scores compared with MPFL repair and nonoperative treatment. MPFL repair led to reduced redislocation rates compared with nonoperative treatment but did not show an obvious benefit in primary dislocations. There was no significant difference among the 3 treatments in terms of revision rate and incidence of complications, although we found that treatment-related complications were least likely to occur in nonoperative treatment.Conclusion:The results of this review indicate that MPFL reconstruction decreases recurrent dislocation compared with MPFL repair or nonoperative treatment, but it has a higher possibility of complications. MPFL repair resulted in less postoperative redislocation than nonoperative treatment but did not show an obvious benefit in primary dislocation.

Network Meta-Analysis Techniques for Synthesizing Prevention Science Evidence.

Network meta-analysis is a popular statistical technique for synthesizing evidence from studies comparing multiple interventions. Benefits of network meta-analysis, over more traditional pairwise meta-analysis approaches, include evaluating efficacy/safety of interventions within a single framework, increased precision, comparing pairs of interventions that have never been directly compared in a trial, and providing a hierarchy of interventions in terms of their effectiveness. Network meta-analysis is relatively underutilized in prevention science. This paper therefore presents a primer of network meta-analysis for prevention scientists who wish to apply this method or to critically appraise evidence from publications using the method. We introduce the key concepts and assumptions of network meta-analysis, namely, transitivity and consistency, and demonstrate their applicability to the field of prevention science. We then illustrate the method using a network meta-analysis examining the comparative effectiveness of brief alcohol interventions for preventing hazardous drinking among college students. We provide data and code for all examples. Finally, we discuss considerations that are particularly relevant in network meta-analyses in the field of prevention, such as including non-randomized evidence.

Comparison of Different Operative Approaches for Lumbar Disc Herniation: A Network Meta- Analysis and Systematic Review

New approaches and technologies can be beneficial for patients but also bring corresponding complications. Traditional pairwise meta-analyses cannot be used to comprehensively rank all surgical approaches. The purpose of this systematic review and network meta-analysis (NMA) was to compare the outcomes of different surgical approaches for lumbar disc herniation (LDH). NMA of randomized controlled trials (RCTs) for multiple treatment comparisons of LDH. The PubMed, Embase, MEDLINE, Ovid, and Cochrane Library databases were searched for RCTs comparing different surgical approaches for patients with LDH from inception to February 10, 2020. The Markov chain Monte Carlo methods were used to perform a hierarchical Bayesian NMA in WinBUGS version 1.4.3 using a random effects consistency model. The primary outcomes were disability and pain intensity. The secondary outcomes were complications and reoperation. The PROSPERO number was CRD42020179406. A total of 22 trials including 2529 patients and all 5 different approaches (open discectomy or microdiscectomy [OD/MD], microendoscopic discectomy [MED], percutaneous endoscopic discectomy [PED], percutaneous discectomy [PD], and tubular discectomy [TD]) were retrospectively retrieved. PED had the best efficacy in improving patients' dysfunction with no statistical significance (probability = 50%). PD was significantly worse than OD/MD, MED, and PED in relieving patients' pain (standardized mean differences: 0.87 [0.03, 1.76], 0.94 [0.06, 1.88], and 1.02 [0.13, 1.94], respectively). There was no statistically significant difference between any 2 surgical approaches in dural tear; intraoperative, postoperative, and overall complications; or reoperation rate. PED had the lowest dural tear rate and the lowest intraoperative and overall complication rates (probability = 51%, 67%, and 33%, respectively). TD had the lowest postoperative complication and reoperation rates (probability = 35% and 39%, respectively). The limitations of this NMA include the inconsistent follow-up times, the criteria for complications, and the reasons for reoperation. Compared with other approaches used to treat LDH, PED had the best safety and efficacy in general, and TD had the lowest reoperation rate. Finally, we recommended PED for LDH.

Phosphodiesterase type-5 inhibitors for erectile dysfunction following nerve-sparing radical prostatectomy: A network meta-analysis.

To verify which phosphodiesterase type 5 inhibitors (PDE5is) strategy is better for erectile dysfunction (ED) following nerve-sparing radical prostatectomy (NSRP). This systematic literature search was conducted in MEDLINE, Web of Science and Cochrane Central Register of Controlled Trials database to identify eligible studies from the startup of these databases to 1 November, 2019. The ED recovery rate was the main outcome. Traditional pair-wise meta-analysis and multivariate random-effects network meta-analysis (NMA) were performed to explore direct and indirect comparisons, respectively. The surface under the cumulative ranking (SUCRA) probabilities was used to evaluate the efficacy of treatments. A total of 14 randomized controlled trials with four kinds of PDE5is were included. Further pooled evidence suggested that PDE5is followed by NSRP had a benefit for penile rehabilitation compared to placebo using traditional pair-wise meta-analyses. Our NMA showed that Avanafil 200 mg on demand might be most likely to be the best treatment option according to the first rank of SUCRA both in NMA (SUCRA 83.5) and sensitivity analysis (SUCRA 90.2). Avanafil 200 mg on demand has the highest probability of being the best intervention among PDE5is in treating ED following NSRP. However, more randomized controlled trials are needed to validate this in consideration of the published data regarding Avanafil is relatively small scale.

Controlled ovarian hyperstimulation for poor ovarian responders undergoing in vitro fertilisation/intracytoplasmic sperm injection: a protocol for systematic review and Bayesian network meta-analysis

IntroductionControlled ovarian hyperstimulation (COH) is the routine regimen used to generate a sufficient number of follicles during in vitro fertilisation (IVF) or intracytoplasmic sperm injection (ICSI) treatment. Poor ovarian response...

Unveiling the comparative efficacy and tolerability of comprehensive treatments for migraine: A protocol of systematic review and Bayesian network meta-analysis.

Background:Migraine is a chronic paroxysmal incapacitating neurological disorder, which endangers the health of human worldwide ranking as the third most prevalent medical condition. There are no comprehensive estimates of treatments for migraine. We will conduct this systematic review and Bayesian network meta-analysis (NMA) to synthesis quantitative and comparative evidence on the efficacy and tolerability of all the known pharmacological and non-pharmacological interventions for migraine.Method:We will perform the systematic electronic search of the literature utilizing MEDLINE, Embase, Cochrane Central Register of Controlled Trials (CENTRAL), Cumulative Index to Nursing & Allied Health (CINAHL), and PsycINFO. We will only include randomized controlled trials (RCTs) of high quality which appraise the efficacy or safety of any potential pharmacological or non-pharmacological interventions in the treatment of patients with migraine. The traditional pairwise meta-analyses will be performed to anticipate the heterogeneities and publication bias and the NMA will be conducted within a Bayesian hierarchical model framework to obtain estimates for all valuable treatments for migraine. The entire heterogeneity will be quantified by Q statistic and I2 index. Other analyses included sensitivity analyses, meta-regression, and subgroup analyses will also be conducted. The whole process will be conducted using in R-3.6.0 software.Results:This study will obtain the efficacy and tolerability of all potential treatments for migraine, aiming at providing consolidated evidence to help make the best choice of interventions. The results will be published in a peer-reviewed journal.Discussion:This Bayesian network meta-analysis may be the first attempt to quantitatively synthesize the efficacy and tolerability of all potential treatments for migraine. And this method can ensure us to fully utilize both the direct and indirect evidence as well as gain the comparative estimates displayed in the derived hierarchies. Besides, we have registered this protocol on the international prospective register of systematic review (PROSPERO) (CRD42020157278).

Non-pharmacological interventions for depressive disorder in patients after traumatic brain injury

Background:Depressive disorder has gradually become one of the most commonly reported disabling psychiatric complication that occurs after traumatic brain injury (TBI). Currently classical antidepressant medications may not have the same effectiveness in patients with TBI as in patients without TBI. Non-pharmacological interventions have been considered to be effective for managing depressive symptoms or treating depressive disorder. But to date the comparative effectiveness of various types of non-pharmacological interventions has been synthesized in few studies, the evidence remains inconclusive. Thus, the purpose of this systematic review and network meta-analyses is to summarize high-quality evidence and identify the most effective non-pharmacological intervention when applied to treat the depressive disorder in patients after TBI.Methods:The comprehensive literature search in electronic database including PubMed, Ovid Medline, Cochrane Library, Web of Science database, Embase Database, China National Knowledge Infrastructure (CNKI), and Wanfang Data Chinese database from inception to the search date. Only high-quality randomized controlled trials (RCTs) that have used non-pharmacological interventions to treat depressive disorder after TBI will be considered. Two independent reviewers will identify eligible studies, extract and manage data information, and then determine methodical quality of included studies. Overall efficacy will be assessed as primary outcome. Secondary outcomes involved treatment response, remission rate, overall acceptability, tolerability of treatment, social functioning, occurrence of adverse events, and suicide-related outcome. Cochrane risk of bias assessment tool will be adopted to assess the risk of bias. Study heterogeneity will be measured by the I2 statistic. Traditional pairwise meta-analyses will be performed using STATA, while WinBUGS with GeMTC package of R software will be used to carry out network meta-analysis.Results:This systematic review will examine the relative efficacy, effectiveness, safety, tolerability and acceptability of non-pharmacological interventions, and then to identify the most effective non-pharmacological intervention for depressive disorder after TBI.Expected conclusion:Our work could be used to give clinical recommendations for practice guideline developers, psychiatrist, neurologist, policymakers, researchers as well as individual with depressive disorder after TBI, and will also identify gaps in knowledge that could be the subject of future research.Ethics and dissemination:Neither ethics approval nor patient informed consent is necessary since this protocol was designed based on the existing literature. The results will be disseminated electronically or in print through publications in peer-reviewed scientific journal.INPLASY registration:INPLASY202080022.

A variance shrinkage method improves arm-based Bayesian network meta-analysis.

Network meta-analysis is a commonly used tool to combine direct and indirect evidence in systematic reviews of multiple treatments to improve estimation compared to traditional pairwise meta-analysis. Unlike the contrast-based network meta-analysis approach, which focuses on estimating relative effects such as odds ratios, the arm-based network meta-analysis approach can estimate absolute risks and other effects, which are arguably more informative in medicine and public health. However, the number of clinical studies involving each treatment is often small in a network meta-analysis, leading to unstable treatment-specific variance estimates in the arm-based network meta-analysis approach when using non- or weakly informative priors under an unequal variance assumption. Additional assumptions, such as equal (i.e. homogeneous) variances for all treatments, may be used to remedy this problem, but such assumptions may be inappropriately strong. This article introduces a variance shrinkage method for an arm-based network meta-analysis. Specifically, we assume different treatment variances share a common prior with unknown hyperparameters. This assumption is weaker than the homogeneous variance assumption and improves estimation by shrinking the variances in a data-dependent way. We illustrate the advantages of the variance shrinkage method by reanalyzing a network meta-analysis of organized inpatient care interventions for stroke. Finally, comprehensive simulations investigate the impact of different variance assumptions on statistical inference, and simulation results show that the variance shrinkage method provides better estimation for log odds ratios and absolute risks.

Comparative Efficacy and Safety of Duration of Dual Antiplatelet Therapy in Patients with CAD Undergoing Drug-eluting Stent Implantation: A Systematic Review and Network Meta-analysis.

The aim was to evaluate the efficacy and safety of duration of dual antiplatelet therapy (DAPT) for patients who received percutaneous coronary intervention (PCI) with a drug-eluting stent. The optimal duration of DAPT to balance the risk of ischemia and bleeding in CAD patients undergoing drug-eluting stent (DES) implantation remains controversial. PubMed, Cochrane Library, Web of Science, Clinicaltrials.gov, CNKI and Wanfang Databases were searched for randomized controlled trials of comparing different durations of DAPT after DES implantation. Primary outcomes were major adverse cardiac and cerebrovascular events (MACCE), and major bleeding, and were pooled by Bayes network meta-analysis. Net adverse clinical and cerebral events were used to estimate the surface under the cumulative ranking (SUCRA) curves. The subgroup analysis based on clinical status, follow-up and area was conducted using traditional pairwise meta-analysis. A total of nineteen trials (n=51,035) were included, involving six duration strategies. The network metaanalysis showed that T2 (<6-month DAPT followed by aspirin, HR:1.51, 95%CI:1.02-2.22), T3 (standard 6-month DAPT, HR:1.47, 95%CI:1.14-1.91), T4 (standard 12-month DAPT, HR:1.41, 95%CI:1.15-1.75) and T5 (18-24 months DAPT, HR:1.47, 95%CI:1.09-1.97) was associated with significantly increased risk of MACCE compared to T6 (>24-month DAPT). However, no significant difference was found in MACCE risk between T1 (<6-month DAPT followed by P2Y12 monotherapy) and T6. Moreover, T5 was associated with significantly increased risk of bleeding compared to T1(RR:3.94, 95%CI:1.66-10.60), T2(RR:3.65, 95%CI:1.32-9.97), T3(RR:1.93, 95%CI:1.21-3.50) and T4(RR:1.89, 95%CI:1.15-3.30). The cumulative probabilities showed that T6(85.0%), T1(78.3%) and T4(44.5%) were the most efficacious treatment compared to the other durations. In the ACS (<50%) subgroup, T1 was observed to significantly reduce the risk of major bleeding compared to T4, but not in the ACS (≥50%) subgroup. Compared with other durations, short DAPT followed by P2Y12 inhibitor monotherapy showed non-inferiority, with a lower risk of bleeding and not associated with an increased MACCE. In addition, the risk of major bleeding increased significantly, starting with DAPT for 18-month. Compared with the short-term treatment, patients with ACS with the standard 12-month treatment have a better prognosis, including lower bleeding rate and the decreased risk of MACCE. Due to study's limitations, the results should be verified in different risk populations.

Comparative efficacy and safety of probiotics for the treatment of irritable bowel syndrome: a systematic review and network meta-analysis protocol

IntroductionIrritable bowel syndrome (IBS) is a common chronic functional gastrointestinal disorder affecting approximately 10% to 25% of the adult population. A large number of clinical trials have been conducted to...

A Meta-Analysis Comparing Aspirin Alone Versus Dual Antiplatelet Therapy for the Prevention of Venous Graft Failure Following Coronary Artery Bypass Surgery

BackgroundAspirin (ASA) monotherapy is the current standard of care after coronary artery bypass grafting (CABG) to prevent saphenous vein graft (SVG) failure. Several small, randomized clinical trials (RCTs) have suggested that dual antiplatelet therapy (DAPT) may be more effective at preventing SVG failure than ASA alone; however, it is unclear whether some P2Y12 inhibitors are more effective than others for the prevention of SVG failure. MethodsScientific databases and websites were searched to find RCTs. Both traditional pairwise meta-analysis using random-effect model and network meta-analysis using mixed-treatment comparison models were performed to compare the efficacy of various anti-platelet strategies for the prevention of SVG failure. ResultsNine RCTs, which included a total of 1677 patients, were analyzed. Compared to ASA alone, DAPT decreased the risk of graft failure by 37% (RR: 0.63, 95% CI: 0.47–0.86; p = 0.003). In the moderator analysis, the decreased risk of graft failure with DAPT was not significantly different in the ASA + clopidogrel group than in the ASA + ticagrelor group (P-interaction = 0.17). The results of the network meta-analysis were consistent with those from pairwise analyses. The risk of major bleeding was not statistically significantly different between DAPT and ASA alone (RR: 1.35, 95% CI: 0.62–2.94; p = 0.45). ConclusionIn post-CABG patients, DAPT seems to be more effective at preventing graft failure than ASA alone. This strategy does not seem to significantly increase major bleeding risk. Clopidogrel- and ticagrelor-based DAPT seem to be equally effective for this indication.

Perspective: Network Meta-analysis Reaches Nutrition Research: Current Status, Scientific Concepts, and Future Directions

Traditional pairwise meta-analysis (PMA) is a very useful method that pools evidence from one study design type if appropriate; its widespread use in nutrition research is an important phenomenon. Recently, a promising method for more advanced evidence-synthesis, called network meta-analysis (NMA), was introduced. NMA is an extension of PMA that enables simultaneous comparison of multiple interventions. NMA combines direct evidence (i.e., trials comparing 2 interventions directly) and indirect evidence (i.e., from a connected route via ≥1 comparators, e.g. placebo) in a network of studies. NMAs have the potential to advance knowledge in the field of nutrition as they provide insights that cannot be obtained by individual 2-arm randomized controlled trials or PMA. Thus, in this perspective paper, we aim to summarize the current (methodologic) status of published NMAs in nutrition research and emphasize advances and strengths in comparison with traditional PMA through specific examples, and highlight potential pitfalls and limitations. NMA is an emerging methodology in the field of nutrition research. A PubMed search identified only 23 nutrition research-related NMAs published since the inception of journals up to January 8, 2019 (61% of them published since 2017), compared with >5000 published PMAs. Moreover, we aim to highlight the scientific concepts and standards through the use of the following NMA example: "Which type of oils/solid fats offers the greatest impact on blood lipids?" In this regard, we discuss intervention definitions, transitivity/similarity, statistical methods, description and visualization of results, inconsistency, ranking, dissemination bias, assessing the certainty of evidence by Grading of Recommendations Assessment, Development and Evaluation, and reporting guidelines. We expect that rigorously conducted NMAs based on high-quality systematic reviews will become the new evidence synthesis benchmark in nutrition research. However, caution is warranted because abuse and misinterpretations of PMA and NMA findings could hamper the scientific field and possibly decision-making regarding public policy.

Relative effectiveness of different forms of exercises for treatment of chronic low back pain: protocol for a systematic review incorporating Bayesian network meta-analysis

IntroductionExercise is considered as an effective intervention in the management of patients with chronic low back pain (cLBP). However, the relative effectiveness as well as the hierarchy of exercise interventions...