Sequential Meta-analysis Research Articles

Antenatal Physical Activity Interventions and Pregnancy Outcomes: A Systematic Review and Meta-Analysis With a Focus on Trial Quality.

Guidelines recommending regular physical activity in pregnancy for improving pregnancy outcomes are informed by published meta-analyses. Inclusion of randomised trials of poor methodological quality may bias effect estimates. To assess the validity of these recommendations by focusing on trial quality. Systematic search of PubMed, PubMed Central, Ovid Medline, Embase, Cochrane Central Register of Controlled Trials, and CINAHL from inception to 14 December 2023. Randomised trials evaluating an antenatal physical activity intervention alone, compared with no such intervention. Trial quality was assessed using the Cochrane Risk of Bias tool. Independent of this, studies were grouped based on degree of deviation from the intention to treat principle. Sequential meta-analysis was performed in which greater degrees of potential bias were allowed. Between intervention group comparisons used, relative risks or mean differences with 95% confidence intervals for dichotomous outcomes and continuous outcomes, respectively. Overall, the quality of trial reporting was low. Only 5 trials (12.5%) were performed and analysed in keeping with the intention to treat principle. When considering only those trials performed rigorously, there was no evidence that antenatal physical activity improves pregnancy outcomes or limits gestational weight gain (WMD -0.60 kg; 95% CI -2.17, 0.98 WMD -0.60 kg; 95% CI -2.17, 0.98). When considering only trials at no/negligible risk of bias, antenatal physical activity interventions were not associated with improved pregnancy outcomes. Most trials were not methodologically rigorous. Incorporation of such meta-analyses into pregnancy care guidelines may result in inaccurate recommendations.

Perioperative administration of sub-anesthetic ketamine/esketamine for preventing postpartum depression symptoms: A trial sequential meta-analysis

Objective Postpartum depression (PPD) is a major mental health issue affecting 10%–15% of women globally. This meta-analysis synthesized updated evidence on sub-anesthetic ketamine/esketamine’s efficacy in preventing PPD. Methods Randomized controlled trials (RCTs) comparing ketamine/esketamine to a placebo for PPD prevention were searched without language restriction. Primary outcomes were PPD risk at 1- and 4–6-week postpartum. Secondary outcomes included the difference in depression scores and risk of adverse events. Trial sequential analysis (TSA) was conducted to validate the reliability. Results A meta-analysis of 22 RCTs (n = 3,463) showed that ketamine/esketamine significantly decreased PPD risk at 1- (risk ratio [RR], 0.41; 95% confidence interval [CI], 0.3–0.57) and 4–6-week (RR, 0.47; 95%CI, 0.35–0.63) follow-ups. Consistently, participants receiving ketamine/esketamine had lower depression-related scores at 1- (standardized mean difference [SMD], −0.94; 95%CI, −1.26 to −0.62) and 4–6-week (SMD, −0.89; 95%CI, −1.25 to −0.53) follow-ups. Despite potential publication bias, TSA confirmed the evidence’s reliability. Subgroup analysis showed that ketamine/esketamine’s preventive effect on 1-week PPD was consistent, regardless of administration timing, type of agents, or total dosage (<0.5 vs. ≥0.5 mg/kg). For the 4–6-week period, PPD risk was favorably reduced only with postoperative administration or the use of esketamine, with the total dosage having no observed influence. Participants on ketamine/esketamine experienced more frequency of hallucinations (RR, 4.77; 95%CI, 1.39–16.44) and dizziness (RR, 1.36; 95%CI, 1.02–1.81). Conclusion Our findings advocate for the postoperative administration of low-dose ketamine/esketamine to avert PPD, which needed additional research for confirmation.

Comparison of efficacy of ultrasound-guided erector spinae plane block versus thoracolumbar interfascial plane block in patients undergoing lumbar spine surgeries: A systematic review and trial sequential meta-analysis.

Existing literature does not establish the superiority of the erector spinae plane (ESP) block or the thoracolumbar interfascial plane (TLIP) block in pain relief and reducing opioid consumption in lumbar spine surgeries. This systematic review and meta-analysis was aimed to discern their relative efficacy and safety. This meta-analysis included randomised controlled trials (RCTs) comparing ESP and TLIP blocks in lumbar spine surgeries. The primary outcome was 24-h opioid consumption, and secondary outcomes were visual analogue scale (VAS) scores at 1 h and 24 h and various complications. PubMed, Central Register of Controlled Trials, SCOPUS, EMBASE databases and cross-references were electronically searched. Two authors extracted data independently, cross-checked, and analysed them using RevMan 5.4. Binary outcomes were reported as odds ratios (OR), while continuous outcomes were presented as standardised mean differences (SMDs) accompanied by 95% confidence intervals (95% CIs). Among 1107 articles, six RCTs (492 patients) were finally included. The ESP block demonstrated lower 24-h opioid consumption compared to TLIP [SMD -0.32 (95% CI: -0.50, -0.14); P < 0.001, I 2 = 83%]. At 1 and 24 h, ESPB yielded significantly lower VAS scores compared to TLIP [1 h: SMD -0.38 (95% CI: -0.57, -0.18); P < 0.001, I 2 = 83%; 24 h: SMD -0.57 (95% CI: -0.76, -0.37); P < 0.001, I 2 = 73%]. No significant difference was noted in adverse events. In comparison to the TLIP block, the ESP block has significantly lower 24-h opioid consumption and VAS scores at 1 and 24 h in patients undergoing lumbar spine surgery.

Critical appraisal and trial sequential meta-analysis for the association of CCND1 G870A gene polymorphism with the risk for colorectal cancer in Asian population

Critical appraisal and trial sequential meta-analysis for the association of CCND1 G870A gene polymorphism with the risk for colorectal cancer in Asian population

Trial Sequential Analysis and Meta-Analysis of Olanzapine in Pediatric Patients for Chemotherapy-Induced Nausea and Vomiting (CINV).

Background and Objective: Olanzapine (OLZ) containing regimens are approved in adults for chemotherapy-induced nausea and vomiting (CINV) receiving highly emetogenic chemotherapy (HEC) or moderately emetogenic chemotherapy (MEC), and the same has not been approved in the pediatric population. In order to generate data regarding the efficacy and safety of OLZ as an adjunct to the standard of care (SoC) for CINV in pediatric patients receiving HEC/MEC, the review authors performed this systematic review and meta-analysis. Methods: A systematic literature search was performed through the databases Cochrane Library, Pub Med, and clinicaltrials.gov, from inception to September 2023, using keywords: "chemotherapy" and "olanzapine," "nausea" and "vomiting." Randomized clinical trials published in English that analyzed the efficacy and safety of olanzapine as an adjunct to SoC were included. The essential outcomes included in this study were the proportion of patients with no emesis in the acute and delayed phase, patients with no nausea in the acute and delayed phase, the proportion of patients requiring rescue medication, and the proportion of patients with reduced CNS arousal. Results: In the OLZ group, a greater number of patients had no emesis both in the acute and delayed phase (RR = 1.22; 95% CI = 1.09-1.37; P = .0004); and (RR = 1.23; 95% CI = 0.92-1.63; P = .16) respectively. Similarly, a higher number of patients showed no nausea both in the acute and delayed phase (RR = 1.08; 95% CI = 0.78-1.48; P = .66) and (RR = 1.12; 95% CI = 0.79-1.61; P = .52) respectively. The use of rescue medication was significantly less in the OLZ group (RR = 0.62; 95% CI = 0.42-0.91; P = .01). More patients experienced reduced CNS arousal in the OLZ group (RR = 2.97; 95% CI = 2.02-4.38; P < .0001). Conclusions: Olanzapine as an adjunct to the SoC may be effective in acute emesis, which may also reduce the use of rescue medication. Reduced CNS alertness was the significant adverse effect observed. For other endpoints, more studies are required to substantiate its role in CINV.

Efficacy of permissive underfeeding for critically ill patients: an updated systematic review and trial sequential meta-analysis

BackgroundOur previous study in 2011 concluded that permissive underfeeding may improve outcomes in patients receiving parenteral nutrition therapy. This conclusion was tentative, given the small sample size. We conducted the present systematic review and trial sequential meta-analysis to update the status of permissive underfeeding in patients who were admitted to the intensive care unit (ICU).MethodsSeven databases were searched: PubMed, Embase, Web of Science, China National Knowledge Infrastructure, Wanfang, Chinese Biomedical Literature Database, and Cochrane Library. Randomized controlled trials (RCTs) were included. The Revised Cochrane risk-of-bias tool (ROB 2) was used to assess the risk of bias in the enrolled trials. RevMan software was used for data synthesis. Trial sequential analyses (TSA) of overall and ICU mortalities were performed.ResultsTwenty-three RCTs involving 11,444 critically ill patients were included. There were no significant differences in overall mortality, hospital mortality, length of hospital stays, and incidence of overall infection. Compared with the control group, permissive underfeeding significantly reduced ICU mortality (risk ratio [RR] = 0.90; 95% confidence interval [CI], [0.81, 0.99]; P = 0.02; I2 = 0%), and the incidence of gastrointestinal adverse events decreased (RR = 0.79; 95% CI, [0.69, 0.90]; P = 0.0003; I2 = 56%). Furthermore, mechanical ventilation duration was reduced (mean difference (MD) = − 1.85 days; 95% CI, [− 3.44, − 0.27]; P = 0.02; I2 = 0%).ConclusionsPermissive underfeeding may reduce ICU mortality in critically ill patients and help to shorten mechanical ventilation duration, but the overall mortality is not improved. Owing to the sample size and patient heterogeneity, the conclusions still need to be verified by well-designed, large-scale RCTs.Trial Registration The protocol for our meta-analysis and systematic review was registered and recorded in PROSPERO (registration no. CRD42023451308). Registered 14 August 2023

A sequential meta-analysis on the effects of microwave ablation on three-year survival of non-small cell lung cancer

A sequential meta-analysis on the effects of microwave ablation on three-year survival of non-small cell lung cancer

Efficacy and safety of collagen derivatives for osteoarthritis: A trial sequential meta-analysis

To investigate the efficacy and safety of collagen derivatives for osteoarthritis. PubMed, Embase, and Cochrane Library were searched till June 2023 for randomized controlled trials (RCTs) investigating collagen derivatives for treating osteoarthritis. Data were independently extracted by two authors. The risk of bias was assessed using the RoB 2 tool. A random-effects meta-analysis was performed within a frequentist framework. The certainty of evidence was evaluated using the Grading of Recommendations, Assessment, Development, and Evaluations approach. A total of 35 RCTs involving 3165 patients were included. The main analysis of the primary outcome was based on 25 RCTs involving 2856 patients. Collagen derivatives exerted small-to-moderate effects on pain alleviation (standardized mean difference [SMD] -0.35, 95% confidence interval [CI] -0.48 to -0.22, moderate certainty) and function improvement (SMD -0.31, 95%CI -0.41 to -0.22, high certainty) compared with the control. Collagen derivatives were safe; they did not increase the risk of withdrawal or adverse events compared with the control. The trial sequential analyses indicated that this study had sufficient statistical power for deriving definitive conclusions, confirming the robustness of our findings. Strong evidence supports the efficacy and safety of collagen derivatives for osteoarthritis treatment.

Efficacy and safety of videolaryngoscopes for transesophageal echocardiography probe insertion: A trial sequential meta-analysis.

This meta-analysis aimed to compare videolaryngoscope (VL)-assisted transesophageal echocardiography (TEE) probe insertion with conventional methods in terms of efficacy and safety. Several major databases such as Medline and Embase were systematically searched to identified relevant studies from inception to June 2024. The primary outcome was complication rate, defined as the proportion of patients experiencing complications related to TEE probe insertion. Injuries at specific sites (e.g., posterior hypopharyngeal wall) from both groups were also analyzed. The secondary outcomes included the first-attempt success rate and total insertion time of VL and conventional methods. Seven trials involving 716 participants were identified. The use of VL was found to significantly reduce the complication rate (risk ratio[RR]:0.28, 95% confidence interval[CI]:0.17-0.46, P < 0.00001) and increased the first-attempt success rate [FASR] (RR:1.33, 95%CI: 1.10-1.60, P = 0.003) compared with conventional methods. These findings were confirmed by trial sequential analysis. No significant difference was found in the TEE insertion time among the two techniques (mean difference: -2.94s, 95%CI: -10.28-4.4, P = 0.43). VL significantly reduced the risk of trauma to the hypopharyngeal wall but showed no significant benefits in other areas (e.g., pyriform sinus). The certainty of evidence was moderate for the complication rate, very low for the FAS rate, and low for the TEE insertion time. The use of VL for TEE probe insertion is associated with a significantly lower complication rate and higher FAS rate than conventional methods. These findings suggest that VL enhances patient safety and improves the efficiency of TEE probe insertion.

The efficacy of Omega-3 polyunsaturated fatty acids for severe burn patients: A systematic review and trial sequential meta-analysis of randomized controlled trials

Severe burns lead to metabolic changes, systemic inflammatory response syndrome, and multiple organ dysfunction syndrome. Omege-3 polyunsaturated fatty acids (PUFAs) have anti-inflammatory properties. In the absence of substantial evidence for use on major burns, we systematically reviewed the efficacy of omega-3 PUFAs for patients with severe burns. We comprehensively searched MEDLINE, Web of Science, Embase, Cochrane Library, China National Knowledge Internet, Wang Fang Data, Chinese Biomedicine Database, and Science Direct databases to collect randomised controlled trials of omega-3 PUFAs administered to patients with burns from January 2000 to June 2023. Two researchers independently screened the literatures, extracted the data, and assessed the risk of bias in the included studies. The outcomes were mortality, the risk of severe sepsis, septic shock, and multiple organ dysfunction syndrome. Data synthesis was conducted using Review Manager. Trial sequential analyses (TSA) for outcomes were performed. Three randomised controlled trials involving 140 patients were included. Of these, 71 patients received omega-3 PUFAs. The results showed that omega-3 PUFAs significantly reduced the incidence of severe sepsis, septic shock, multiple organ dysfunction syndrome (RR=0.38, 95% CI [0.19, 0.75], P=0.005), C-reactive protein levels (MD=-39.70[-81.63, 2.23], P=0.06), and improved respiratory outcomes. However, there was no difference in 14-day mortality (RR=1.10, 95%CI [0.59, 2.05], P=0.75). TSA showed that the results for the incidence of severe sepsis, septic shock, multiple organ dysfunction syndrome are insufficient and inconclusive. Omega-3 PUFAs may reduce inflammatory response and risk of sepsis, septic shock, and multiple organ dysfunction syndrome in severe burns patients and may shorten hospital stay but cannot reduce risk of death. Due to the limitation of the quantity and quality of the included studies, the evidence level is low, and the conclusions need to be verified by larger scale and higher quality randomised controlled trials.

Epicardial adipose tissue in patients with chronic obstructive pulmonary disease: systematic review with meta‑analysis and trial sequential analysis

BackgroundLimited data suggest that chronic obstructive pulmonary disease (COPD) patients have pathologic elevated epicardial adipose tissue (EAT), which is splanchnic fat tissue with anti-inflammatory properties and regulating free fatty acids functions. Therefore, there is a need for meta-analysis to explore the relationship between EAT and COPD.MethodsOnline databases were systematically searched for studies about EAT in COPD patients published up to October 5th, 2022. The EAT data of the COPD patient group and the control group were included. Trial sequential analysis (TSA) and meta-analysis were applied to assess the difference in EAT between patients with and without COPD. TSA software and Stata 12.0 were used in all statistical analyses.ResultsThe final analysis included 5 studies (n = 596 patients). COPD patients had significantly more EAT than control subjects (SMD: 0.0.802; 95% CI: 0.231, 1.372; P = 0.006; TSA-adjusted 95% CI 1.20, 1.80; P < 0.0001). And higher CRP levels in COPD patients than non-COPD patients, whereas triglycerides and LDL were not significantly different between patients with and without COPD.ConclusionEAT is abnormally elevated in COPD patients, which may be related to systemic inflammatory responses in COPD.PROSPERO numberCRD42021228273.

Clinical outcomes of intravenous iron therapy in patients with heart failure and iron deficiency: Meta-analysis and trial sequential analysis of randomized clinical trials

BackgroundIron deficiency in patients with heart failure (HF) is underdiagnosed and undertreated. The role of intravenous (IV) iron is well-established to improve quality of life measures. Emerging evidence also supports its role in preventing cardiovascular events in patients with HF. MethodologyWe conducted a literature search of multiple electronic databases. Randomized controlled trials that compared IV iron to usual care among patients with HF and reported cardiovascular (CV) outcomes were included. Primary outcome was the composite of first heart failure hospitalization (HFH) or CV death. Secondary outcomes included HFH (first or recurrent), CV death, all-cause mortality, hospitalization for any cause, gastrointestinal (GI) side effects, or any infection. We performed trial sequential and cumulative meta-analyses to evaluate the effect of IV iron on the primary endpoint, and on HFH. ResultsNine trials enrolling 3337 patients were included. Adding IV iron to usual care significantly reduced the risk of first HFH or CV death [risk ratio (RR) 0.84; 95 % confidence interval (CI) 0.75–0.93; I2 = 0 %; number needed to treat (NNT) 18], which was primarily driven by a reduction in the risk of HFH of 25 %. IV iron also reduced the risk of the composite of hospitalization for any cause or death (RR 0.92; 95 % CI 0.85–0.99; I2 = 0 %; NNT 19). There was no significant difference in the risk of CV death, all-cause mortality, adverse GI events, or any infection among patients receiving IV iron compared to usual care. The observed benefits of IV iron were directionally consistent across trials and crossed both the statistical and trial sequential boundaries of benefit. ConclusionIn patients with HF and iron deficiency, the addition of IV iron to usual care reduces the risk of HFH without affecting the risk of CV or all-cause mortality.

Value of immunonutrition in patients undergoing pancreatic resection: a trial sequential meta-analysis

BackgroundThe benefits of immunonutrition (IM) in patients who underwent pancreatic surgery are unclear. MethodsA meta-analysis of randomized clinical trials (RCTs) comparing IM with standard nutrition (SN) in pancreatic surgery was carried out. A random-effects trial sequential meta-analysis was made, reporting Risk Ratio (RR), mean difference (MD), and required information size (RIS). If RIS was reached, false negative (type II error) and positive results (type I error) could be excluded. The endpoints were morbidity, mortality, infectious complication, postoperative pancreatic fistula (POPF) rates, and length of stay (LOS). ResultsThe meta-analysis includes 6 RCTs and 477 patients. Morbidity (RR 0.77; 0.26 to 2.25), mortality (RR 0.90; 0.76 to 1.07), and POPF rates were similar. The RISs were 17,316, 7,417, and 464,006, suggesting a type II error. Infectious complications were lower in the IM group, with a RR of 0.54 (0.36–0.79; 95 CI). The LOS was shorter in IM (MD -0.3 days; −0.6 to −0.1). For both, the RISs were reached, excluding type I error. ConclusionThe IM can reduce infectious complications and LOS The small differences in mortality, morbidity, and POPF make it impossible to exclude type II error due to large RISs.

Protocol for a Systematic Review and Individual Participant Data Meta-Analysis of Randomized Trials of Screening for Atrial Fibrillation to Prevent Stroke.

Atrial fibrillation (AF) is a common cause of stroke. Timely diagnosis of AF and treatment with oral anticoagulation (OAC) can prevent up to two-thirds of AF-related strokes. Ambulatory electrocardiographic (ECG) monitoring can identify undiagnosed AF in at-risk individuals, but the impact of population-based ECG screening on stroke is uncertain, as ongoing and published randomized controlled trials (RCTs) have generally been underpowered for stroke. The AF-SCREEN Collaboration, with support from AFFECT-EU, have begun a systematic review and individual participant data meta-analysis of RCTs evaluating ECG screening for AF. The primary outcome is stroke. Secondary outcomes include AF detection, OAC prescription, hospitalization, mortality, and bleeding.After developing a common data dictionary, anonymized data will be collated from individual trials into a central database. We will assess risk of bias using the Cochrane Collaboration tool, and overall quality of evidence with the Grading of Recommendations Assessment, Development and Evaluation approach.We will pool data using random effects models. Prespecified subgroup and multilevel meta-regression analyses will explore heterogeneity. We will perform prespecified trial sequential meta-analyses of published trials to determine when the optimal information size has been reached, and account for unpublished trials using the SAMURAI approach. Individual participant data meta-analysis will generate adequate power to assess the risks and benefits of AF screening. Meta-regression will permit exploration of the specific patient, screening methodology, and health system factors that influence outcomes. PROSPERO CRD42022310308.

Trial Sequential Analysis and Updated Meta-Analysis of Fluvoxamine on Clinical Deterioration in Adult Patients with Symptomatic COVID-19 Infection

Preliminary meta-analyses suggested that fluvoxamine was effective in treating COVID-19 infection. However, the reliability of this evidence has not yet been examined. MEDLINE, CENTRAL, EMBASE, PsycINFO, and ClinicalTrials.gov were searched to identify any randomized controlled trials (RCTs) from the inception of the databases to 5 February 2023. We used trial sequential analysis (TSA) to examine the reliability of the current existing evidence on the benefits of fluvoxamine on COVID-19 infection. The primary outcome was clinical deterioration, as defined in the original study (reported as odds ratio (OR), with 95% confidence intervals), and the secondary outcome was hospitalization. In the TSA, we used the relative risk reduction thresholds of 10, 20, and 30%. The updated meta-analysis of the five RCTs showed that fluvoxamine was not associated with lower odds of clinical deterioration when compared with a placebo (OR: 0.81; 0.59-1.11). The effect of fluvoxamine lay within the futility boundary (i.e., lack of effect) when using a 30% relative risk reduction threshold. The effect estimates lay between the superiority and futility boundary using the 10% and 20% threshold, and the required size of information was not reached for these two thresholds. The effect of fluvoxamine on the odds of hospitalization was not statistically significant (0.76; 0.56-1.03). In conclusion, there is no reliable evidence that fluvoxamine, when compared to a placebo, reduces the relative risk of clinical deterioration among adult patients with COVID-19 infection by 30%, and a relative risk reduction of 20% or 10% is still uncertain. The role of fluvoxamine as a COVID-19 treatment cannot be justified.

Feedback for Promoting Motor Skill Learning in Physical Education: A Trial Sequential Meta-Analysis.

Feedback can be used as an effective teaching method in physical education (PE) to promote students' learning of motor skills. However, there is no objective synthetic evidence to support the role of feedback in PE. Additionally, the effect of each feedback subtype on students' motor skill learning is still unclear. This study aimed to conduct a meta-analysis and trial sequential analysis (TSA) to evaluate the effects of feedback and feedback subtypes on students' motor skill learning. Nine databases were searched through September 2022 to identify appropriate literature. Meta-analysis was conducted using Review Manager 5.4 software and TSA was performed using TSA version 0.9.5.10 beta software. Fifteen studies were included. Feedback significantly improved students' motor skill learning in PE (SMD 0.47; 95% CI 0.01, 0.93; Z = 2.02; p = 0.04). The TSA confirmed the result of the meta-analysis. Sensitivity analyses showed that the subtypes of feedback, including visual feedback, visual combined verbal feedback, visual self-model, visual expert model, corrective feedback, and teacher-regulated feedback, significantly improved students' learning of motor skills. In contrast, verbal, evaluative, and informational feedback did not produce changes in motor skill learning. Both complex and simple motor skills were improved by feedback. The use of feedback in PE benefits motor skill learning, regardless of whether the motor skills are complex or simple.

Comparative effectiveness and safety of open triple-branched stent graft technique with stented elephant trunk implantation in treating Stanford type A aortic dissection: A trial sequential meta-analysis.

The optimal surgical intervention for Stanford type A aortic dissection is controversial. The aim of this trial sequential meta-analysis was to investigate the comparative effectiveness and safety of open triple-branched stent graft and stent elephant trunk implantation for total aortic arch reconstruction in Sandford type A aortic dissection. PubMed, Embase, Cochrane library, Chinese Biomedical Literature database (CBM), and China National Knowledge Infrastructure (CNKI) were searched for retrieving relevant studies from inception to February 28, 2022. We evaluated 30-day mortality, procedure-related time including cardiopulmonary bypass (CPB), aortic cross-clamp (ACC), and selective cerebral perfusion (SCP),the incidence of postoperative complications including paralysis, cerebral embolism, and acute renal failure, intensive care unit (ICU) time, and medical expenditure. Statistical analysis was performed by RevMan 5.4 and trial sequential analysis (TSA) software. Six studies involving 260 dissection cases were included eventually. Total aortic arch reconstruction with open triple-branched stent graft was comparable to the stented elephant trunk implantation in 30-day mortality, incidence of postoperative complications, ICU time, and medical expenditure, but open triple-branched stent graft was related to shorter procedure-related time including CPB (mean difference [MD] = -46.11, 95% confidence interval [CI] = -67.24 to -24.98, p < .001), ACC (MD = -42.82, 95%CI = -66.74 to -18.90, p < .001), and SCP (MD = -17.88, 95%CI = -33.36 to -2.39, p = .02). TSA confirmed robustness of findings. Our analysis suggested that total aortic arch reconstruction with open triple-branched stent graft may be an effective and simplified procedure than the stented elephant trunk implantation.

Estimating the sample size of sham-controlled randomized controlled trials using existing evidence.

Background: In randomized controlled trials (RCTs), the power is often 'reverse engineered' based on the number of participants that can realistically be achieved. An attractive alternative is planning a new trial conditional on the available evidence; a design of particular interest in RCTs that use a sham control arm (sham-RCTs). Methods: We explore the design of sham-RCTs, the role of sequential meta-analysis and conditional planning in a systematic review of renal sympathetic denervation for patients with arterial hypertension. The main efficacy endpoint was mean change in 24-hour systolic blood pressure. We performed sequential meta-analysis to identify the time point where the null hypothesis would be rejected in a prospective scenario. Evidence-based conditional sample size calculations were performed based on fixed-effect meta-analysis. Results: In total, six sham-RCTs (981 participants) were identified. The first RCT was considerably larger (535 participants) than those subsequently published (median sample size of 80). All trial sample sizes were calculated assuming an unrealistically large intervention effect which resulted in low power when each study is considered as a stand-alone experiment. Sequential meta-analysis provided firm evidence against the null hypothesis with the synthesis of the first four trials (755 patients, cumulative mean difference -2.75 (95%CI -4.93 to -0.58) favoring the active intervention)). Conditional planning resulted in much larger sample sizes compared to those in the original trials, due to overoptimistic expected effects made by the investigators in individual trials, and potentially a time-effect association. Conclusions: Sequential meta-analysis of sham-RCTs can reach conclusive findings earlier and hence avoid exposing patients to sham-related risks. Conditional planning of new sham-RCTs poses important challenges as many surgical/minimally invasive procedures improve over time, the intervention effect is expected to increase in new studies and this violates the underlying assumptions. Unless this is accounted for, conditional planning will not improve the design of sham-RCTs.

An Updated Trial Sequential Meta-analysis of Vitamin D Receptor Gene Polymorphism (Fok1, Bsm1, Taq1 and Apa1) and Risk to Tuberculosis.

The online version contains supplementary material available at 10.1007/s12291-022-01091-3.

Trial sequential meta-analysis of laparoscopic versus open pancreaticoduodenectomy: is it the time to stop the randomization?

BackgroundThe advantages of LPD compared with OPD remain debatable. The study aimed to compare the laparoscopic (LPD) versus open (OPD) for pancreaticoduodenectomy.MethodsA meta-analysis of randomized studies (RCTs) comparing LPD and OPD was made. The results were reported as relative risk (RRs) or mean differences (MDs). The trial sequential analysis was used to test the type I and type II errors defining the required information size (RIS). The primary outcome was mortality, major morbidity, and postoperative pancreatic fistula (POPF). R1 resection, post-pancreatectomy hemorrhage, delayed gastric emptying, biliary fistula, reoperation, readmission, operative time (OT), lymph nodes harvested, and length of stay (LOS) were also studied.ResultsFour RCTs, counting 818 patients, were found. The RRs for mortality, major morbidity, and POPF were 1.16, 1.04, and 0.86, without significant differences. The RISs were 35,672, 16,548, and 8206. To confirm this equivalence, at least 34,854, 15,730, and 7338 should be randomized. OT was significantly longer in LPD than OPD, with an MD of 63.22. The LOS was significantly shorter in LPD than in OPD, with − 1.76 days. The RISs were 1297 and 1273, excluding a false-positive result. No significant differences were observed for the remaining endpoints, and RISs suggested that more than 3000 patients should be randomized to confirm the equivalence.ConclusionThe equivalence of LPD and OPD for mortality, major morbidity, and POPF is affected by type II error. The RISs to demonstrate a superiority of one of the two techniques seem unrealistic to obtain.