Effect of electronic alerts on the care and outcomes in patients with acute kidney injury: a meta-analysis and trial sequential analysis.

BACKGROUND: Although electronic alerts are being increasingly implemented in patients with acute kidney injury (AKI), their effect remains unclear. Therefore, we conducted this meta-analysis aiming at investigating their impact on the care and outcomes of AKI patients. METHODS: PubMed, Embase, Cochrane Library, and Clinical Trial Registries databases were systematically searched for relevant studies from inception to March 2024. Randomized controlled trials comparing electronic alerts with usual care in patients with AKI were selected. RESULTS: Six studies including 40,146 patients met the inclusion criteria. The pooled results showed that electronic alerts did not improve mortality rates (relative risk (RR) = 1.02, 95% confidence interval (CI) = 0.97-1.08, P = 0.44) or reduce creatinine levels (mean difference (MD) = - 0.21, 95% CI = - 1.60-1.18, P = 0.77) and AKI progression (RR = 0.97, 95% CI = 0.90-1.04, P = 0.40). Instead, electronic alerts increased the odds of dialysis and AKI documentation (RR = 1.14, 95% CI = 1.05-1.25, P = 0.002; RR = 1.21, 95% CI = 1.01-1.44, P = 0.04, respectively), but the trial sequential analysis (TSA) could not confirm these results. No differences were observed in other care-centered outcomes including renal consults and investigations between the alert and usual care groups. CONCLUSIONS: Electronic alerts increased the incidence of AKI and dialysis in AKI patients, which likely reflected improved recognition and early intervention. However, these changes did not improve the survival or kidney function of AKI patients. The findings warrant further research to comprehensively evaluate the impact of electronic alerts.

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

OBJECTIVE: To investigate the efficacy and safety of collagen derivatives for osteoarthritis. DESIGN: 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. RESULTS: 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. CONCLUSIONS: Strong evidence supports the efficacy and safety of collagen derivatives for osteoarthritis treatment.

B vitamins and bone health: a meta-analysis with trial sequential analysis of randomized controlled trials.

Our study showed that B vitamins did not have significant effect on fracture incidence, bone mineral density, and bone turnover markers. However, the research data of B vitamins on bone mineral density and bone turnover markers are limited, and more clinical trials are needed to draw sufficient conclusions. PURPOSE: The objective of this study was to identify the efficacy of B vitamin (VB) (folate, B6, and B12) supplements on fracture incidence, bone mineral density (BMD), and bone turnover markers (BTMs). METHODS: A comprehensive search was performed in PubMed, MEDLINE, EMBASE, Cochrane databases, and ClinicalTrials.gov up to September 4, 2023. The risk of bias was assessed according to Cochrane Handbook and the quality of evidence was assessed according to the GRADE system. We used trial sequential analysis (TSA) to assess risk of random errors and Stata 14 to conduct sensitivity and publication bias analyses. RESULTS: Data from 14 RCTs with 34,700 patients were extracted and analyzed. The results showed that VBs did not significantly reduce the fracture incidence (RR, 1.06; 95% CI, 0.95 - 1.18; p = 0.33; I2 = 40%) and did not affect BMD in lumbar spine and femur neck. VBs had no significant effect on bone specific alkaline phase (a biomarker for bone formation), but could increase the serum carboxy-terminal peptide (a biomarker for bone resorption) (p = 0.009; I2 = 0%). The TSA showed the results of VBs on BMD and BTMs may not be enough to draw sufficient conclusions due to the small number of sample data included and needed to be demonstrated in more clinical trials. The inability of VBs to reduce fracture incidence has been verified by TSA as sufficient. Sensitivity analysis and publication bias assessment proved that our meta-analysis results were stable and reliable, with no significant publication bias. CONCLUSIONS: Available evidence from RCTs does not support VBs can effectively influence osteoporotic fracture risk, BMD, and BTMs. TRIAL REGISTRATION: PROSPERO registration number: CRD42023427508.

Efficacy of hemostatic powder monotherapy versus conventional endoscopic treatment for nonvariceal gastrointestinal bleeding: a meta-analysis and trial sequential analysis.

BACKGROUND AND AIMS: Hemostatic powder (HP) is a novel hemostasis modality for nonvariceal gastrointestinal (GI) bleeding. The meta-analysis was performed to evaluate the efficacy of HP monotherapy versus conventional endoscopic treatment (CET) for nonvariceal GI bleeding. METHODS: PubMed, Embase, and Cochrane Library databases were systematically searched from inception to October 16, 2023. The primary outcomes were the initial hemostatic rate and the 30-day rebleeding rate. After the meta-analysis, the trial sequential analysis (TSA) was also conducted to decrease the risk of random errors and validate the result. RESULTS: The meta-analysis included eight studies, incorporating 653 patients in total. Given significant heterogeneity, all analyses were segregated into malignancy-related and non-malignancy-related GI bleeding lesions. For the former, HP monotherapy significantly improved the initial hemostasis rate and 30-day rebleeding rate compared to CET (Relative risk [RR] 1.50, 95% confidence interval [CI] 1.28 - 1.75, P < .001; RR .32, 95% CI .12 - .86, P = .02), and TSA supported the above results. For non-malignancy-related GI bleeding, HP monotherapy and CET have similar initial hemostasis and 30-day rebleeding rates (RR 1.08, 95% CI .98 - 1.19, P = .11; RR 1.15, 95% CI .46 - 2.90, P = .76), but the TSA failed to confirm the above results. CONCLUSIONS: In conclusion, HP monotherapy surpassed CET in terms of the initial hemostasis rate and 30-day rebleeding rate for patients with malignancy-related GI bleeding. However, their relative efficacy for non-malignancy-related GI bleeding remains unresolved.

Effects and safety of hyaluronic acid gel on intrauterine adhesion and fertility after intrauterine surgery: a systematic review and meta-analysis with trial sequential analysis of randomized controlled trials.

OBJECTIVE: This study aimed to determine the efficacy and safety of hyaluronic acid gel for the prevention of intrauterine adhesions and improved fertility after intrauterine surgery. DATA SOURCES: PubMed, EMBASE, Cochrane Library, Web of science, and ClinicalTrials.gov were searched up to November 1, 2023. STUDY ELIGIBILITY CRITERIA: Randomized controlled trials that reported intrauterine adhesion and fertility outcomes among women who used hyaluronic acid after intrauterine surgery. METHODS: The risk of bias was assessed using criteria of the Cochrane Handbook, and the quality of the evidence was evaluated using the Grades of Recommendation, Assessment, Development, and Evaluation system. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines were followed. A trial sequential analysis was conducted to assess the outcomes, and Stata 14 was used for sensitivity analyses and publication bias analyses. RESULTS: Data from 16 randomized controlled trials involving 2359 patients were extracted and analyzed. The analysis revealed that hyaluronic acid reduced the incidence of intrauterine adhesion (risk ratio, 0.53; 95% confidence interval, 0.42-0.67; I2=48%) and improve pregnancy rates (risk ratio, 1.24; 95% confidence interval, 1.02-1.50; I2=0%). A subgroup analysis was conducted to evaluate factors that influence the effect of hyaluronic acid on the incidence of intrauterine adhesion. It was found that a small volume of hyaluronic acid reduced the incidence of intrauterine adhesions. Hyaluronic acid exhibited a protective effect among patients who underwent various intrauterine surgeries and who had different gynecologic medical histories. The protective effect was statistically significant after a follow-up of 6 to 12 weeks. The results of the trial sequential analysis indicated that the effect of hyaluronic acid on the incidence of mild intrauterine adhesions, pregnancy rates, live birth rates, and miscarriage rates after intrauterine surgery may be inconclusive and thus further evaluation is required in the form of additional clinical trials. However, the remaining effects were found to be verifiable and did not require more clinical trials for confirmation. CONCLUSION: Hyaluronic acid can safely and effectively reduce the incidence of intrauterine adhesions and may improve fertility outcomes.

Dendritic cell vaccine for glioblastoma: an updated meta-analysis and trial sequential analysis.

BACKGROUND: Dendritic cell (DC) vaccine is an emerging immunotherapy that could potentially improve glioblastoma survival. The first phase III clinical trial of DC vaccine was recently published. This meta-analysis aims to update and reappraise existing evidence on the efficacy of DC vaccine in patients with glioblastoma. METHODS: We searched PubMed, Embase, and Cochrane Library for clinical trials of DC vaccine for glioblastoma. The quality of the studies was assessed using the RoB 2.0 and ROBINS-I tools. The results of overall survival (OS) and progression-free survival (PFS) were pooled using hazard ratios (HRs) with corresponding 95% confidence intervals (CI). Summary effects were evaluated using random effects models. Trial sequential analysis (TSA) was performed. RESULTS: Seven clinical trials involving 3,619 patients were included. DC vaccine plus standard care was associated with significantly improved OS (HR = 0.71; 95% CI, 0.57 - 0.88) and PFS (HR = 0.65; 95% CI, 0.43 - 0.98). In the subgroup of newly diagnosed glioblastoma, DC vaccine was associated with improved PFS (HR = 0.59; 95% CI, 0.39 - 0.90). TSA of OS showed that the cumulative z-score line for the DC vaccine crossed the benefit boundary and reached the required sample size. TSA of PFS and subgroup analysis of newly diagnosed glioblastoma showed that the required sample size was not reached. CONCLUSIONS: This updated meta-analysis, which included the first phase III trial of a DC vaccine for glioblastoma, demonstrated that the DC vaccine was associated with improved OS. Moreover, TSA showed that the required sample size was reached, indicating a true-positive result. Future studies are required for patient subgroups with newly diagnosed and recurrent glioblastoma.

Nirmatrelvir/Ritonavir Regimen for Mild/Moderately Severe COVID-19: A Rapid Review With Meta-Analysis and Trial Sequential Analysis.

BACKGROUND: The efficacy, effectiveness, and safety of the approved nirmatrelvir/ritonavir regimen for treatment of laboratory-confirmed mild/moderately severe COVID-19 remains unclear. METHODS: We systematically identified randomized controlled trials (RCTs) and real-world studies (RWS; observational studies) of the efficacy/effectiveness and/or safety of the approved nirmatrelvir/ritonavir regimen for COVID-19. We pooled appropriate data (adjusted estimates for RWS) using an inverse variance, random-effects model. We calculated statistical heterogeneity using the I 2 statistic. Results are presented as relative risk (RR) with associated 95% CI. We further assessed risk of bias/study quality and conducted trial sequential analysis of the evidence from RCTs. RESULTS: We included 4 RCTs (4,070 persons) and 16 RWS (1,925,047 persons) of adults (aged ≥18 years). One and 3 RCTs were of low and unclear risk of bias, respectively. The RWS were of good quality. Nirmatrelvir/ritonavir significantly decreased COVID-19 hospitalization compared with placebo/no treatment (RR = 0.17; 95% CI, 0.10-0.31; I 2 = 77.2%; 2 RCTs, 3,542 persons), but there was no significant difference for decrease of worsening severity (RR = 0.82; 95% CI, 0.66-1.01; I 2 = 47.5%; 3 RCTs, 1,824 persons), viral clearance (RR = 1.19; 95% CI, 0.93-1.51; I 2 = 82%; 2 RCTs, 528 persons), adverse events (RR = 1.41; 95% CI, 0.92-2.14; I 2 = 70.6%; 4 RCTs, 4,070 persons), serious adverse events (RR = 0.82; 95% CI, 0.41-1.62; I 2 = 0%; 3 RCTs, 3,806 persons), and all-cause mortality (RR = 0.27; 95% CI, 0.04-1.70; I 2 = 49.9%; 3 RCTs, 3,806 persons), although trial sequential analysis suggested that the current total sample sizes for these outcomes were not large enough for conclusions to be drawn. Real-world studies also showed significantly decreased COVID-19 hospitalization (RR = 0.48; 95% CI, 0.37-0.60; I 2 = 95.0%; 11 RWS, 1,421,398 persons) and all-cause mortality (RR = 0.24; 95% CI, 0.14-0.34; I 2 = 65%; 7 RWS, 286,131 persons) for nirmatrelvir/ritonavir compared with no treatment. CONCLUSIONS: Nirmatrelvir/ritonavir appears to be promising for preventing hospitalization and potentially decreasing all-cause mortality for persons with mild/moderately severe COVID-19, but the evidence is weak. More studies are needed.

Major mistakes or errors in the use of trial sequential analysis in systematic reviews or meta-analyses - the METSA systematic review.

BACKGROUND: Systematic reviews and data synthesis of randomised clinical trials play a crucial role in clinical practice, research, and health policy. Trial sequential analysis can be used in systematic reviews to control type I and type II errors, but methodological errors including lack of protocols and transparency are cause for concern. We assessed the reporting of trial sequential analysis. METHODS: We searched Medline and the Cochrane Database of Systematic Reviews from 1 January 2018 to 31 December 2021 for systematic reviews and meta-analysis reports that include a trial sequential analysis. Only studies with at least two randomised clinical trials analysed in a forest plot and a trial sequential analysis were included. Two independent investigators assessed the studies. We evaluated protocolisation, reporting, and interpretation of the analyses, including their effect on any GRADE evaluation of imprecision. RESULTS: We included 270 systematic reviews and 274 meta-analysis reports and extracted data from 624 trial sequential analyses. Only 134/270 (50%) systematic reviews planned the trial sequential analysis in the protocol. For analyses on dichotomous outcomes, the proportion of events in the control group was missing in 181/439 (41%), relative risk reduction in 105/439 (24%), alpha in 30/439 (7%), beta in 128/439 (29%), and heterogeneity in 232/439 (53%). For analyses on continuous outcomes, the minimally relevant difference was missing in 125/185 (68%), variance (or standard deviation) in 144/185 (78%), alpha in 23/185 (12%), beta in 63/185 (34%), and heterogeneity in 105/185 (57%). Graphical illustration of the trial sequential analysis was present in 93% of the analyses, however, the Z-curve was wrongly displayed in 135/624 (22%) and 227/624 (36%) did not include futility boundaries. The overall transparency of all 624 analyses was very poor in 236 (38%) and poor in 173 (28%). CONCLUSIONS: The majority of trial sequential analyses are not transparent when preparing or presenting the required parameters, partly due to missing or poorly conducted protocols. This hampers interpretation, reproducibility, and validity. STUDY REGISTRATION: PROSPERO CRD42021273811.

Bidirectional associations between periodontitis and inflammatory bowel disease: A systematic review of longitudinal studies with meta-analysis and trial sequential analysis.

The bidirectional associations between periodontitis and inflammatory bowel disease (IBD) with temporal directionality remain inconclusive. This study aims to evaluate the bidirectional associations between periodontitis and IBD through a systematic review and meta-analysis. Five databases (PubMed, Embase, Web of Science, Scopus and Cochrane Library) were systematically searched from inception to 27 February 2024. Two independent reviewers performed a review of the retrieved studies. Longitudinal studies, including cohort and nested case-control studies, were considered eligible for the study design. The pooled risk ratio (RR) and hazard ratio (HR) derived from the meta-analysis were used to assess whether periodontitis (or IBD) was a risk factor for IBD (or periodontitis). Trial sequential analysis (TSA) was performed to evaluate the reliability of the results. Four studies (n = 10 270 912) on the risk of IBD in patients with periodontitis and two (n = 33 420) on the risk of periodontitis in patients with IBD were included. The result suggested that periodontitis did not increase the risk of IBD (pooled RR = 1.04, 95% confidence interval [CI]: 0.99-1.09; p = .164; I-squared statistic [I2] = 27%). For subtypes of IBD, periodontitis was associated with the occurrence of ulcerative colitis (UC) (pooled RR = 1.12, 95% CI: 1.04-1.21; p = .003; I2 = 38%), but not with Crohn's disease (CD) (pooled RR = 0.98, 95% CI: 0.92-1.04; p = .475; I2 = 0%). Specifically, the risk of UC was higher among men (pooled HR = 1.11, 95% CI: 1.01-1.22; p = .025; I2 = 0%) and smokers (pooled HR = 1.23, 95% CI: 1.07-1.42; p = .004; I2 = 0%) with periodontitis than their counterparts without periodontitis. Patients with IBD may have a higher risk of developing periodontitis (pooled HR = 1.37, 95% CI: 1.26-1.49; p < .001; I2 = 18%); however, whether IBD subtypes increased the occurrence of periodontitis remained uncertain. The TSA results confirmed the reliability of the primary findings. Based on limited longitudinal evidence, patients with periodontitis do not exhibit an increased risk of developing IBD overall, but they are at increased risk of UC (not CD). On the contrary, patients with IBD have a higher risk of developing periodontitis over time. More high-quality longitudinal studies are needed to determine the effect of specific subtypes of IBD on periodontitis.

Prophylactic dexamethasone for rebound pain after peripheral nerve block in adult surgical patients: systematic review, meta-analysis, and trial sequential analysis of randomised controlled trials.

BACKGROUND: Rebound pain occurs after the resolution of peripheral nerve block and hampers patient recovery in the postoperative period. We sought to synthesise available data from randomised controlled trials (RCTs) evaluating the efficacy of prophylactic dexamethasone for rebound pain in adult patients undergoing surgery with a peripheral nerve block. METHODS: In this systematic review and meta-analysis, RCTs reporting rebound pain and use of dexamethasone in the context of a peripheral nerve block were searched in various databases and updated in May 2023. The primary outcome was the incidence of rebound pain; secondary outcomes included the severity and time to onset of rebound pain, patient satisfaction with pain control, sleep disturbance because of pain, and adverse effects of dexamethasone. Subgroup analysis was conducted based on the effect of route of administration (intravenous or perineural) on the incidence of rebound pain. Trial sequential analysis was performed to rule out the possibility of a false positive result. RESULTS: Seven RCTs comprising 574 patients were included in this review. The dexamethasone group was associated with a reduction in the incidence of rebound pain with an odds ratio of 0.16 (95% confidence interval 0.10-0.27, P=0.00, I2=0%) compared with the control group. Trial sequential analysis confirmed the adequate information size for the beneficial effect of dexamethasone. Subgroup analysis showed that both intravenous and perineural administration were associated with a significant reduction in the incidence of rebound pain. CONCLUSIONS: Current evidence suggests that both intravenous and perineural dexamethasone reduce the incidence of rebound pain after a peripheral nerve block provided for postoperative analgesia. SYSTEMATIC REVIEW PROTOCOL: PROSPERO CRD42023424031.

Association of Molar Incisor Hypomineralization with Hypomineralized Second Primary Molars: An Updated Systematic Review with a Meta-Analysis and Trial Sequential Analysis.

INTRODUCTION: There is a correlation between molar incisor hypomineralization (MIH) and hypomineralized second primary molars (HSPM), but this relationship has not been definitively confirmed. The purpose of this systematic review and meta-analysis was to reevaluate whether children with HSPM are more affected by MIH than non-HSPM children. METHODS: A systematic search was conducted in four databases (PubMed, Embase, Web of Science, and the Cochrane Library) for literature, published up to December 2022. Two independent reviewers conducted the study search and screening, quality assessment, and data extraction according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. The risk-of-bias assessment of all included cohort studies and case-control studies was assessed by the Newcastle-Ottawa Scale (NOS), and cross-sectional studies were assessed using the Agency for Healthcare Research Quality (AHRQ) scale. RevMan 5.4 software was used for all data analyses, with odds ratios (ORs) and 95% confidence intervals (CIs) as the effect measures. Sensitivity and subgroup analyses were conducted to identify the potential sources of heterogeneity among the studies. Publication bias was tested and corrected by funnel plots and Egger's test. Trial sequential analysis (TSA) was performed using TSA 0.9.5.10 Beta software to control for type-1 and type-2 errors. RESULTS: A total of 12 studies involving 8,944 children were included in this meta-analysis. Compared with the non-HSPM group, the HSPM group had an increased likelihood of MIH (OR = 10.90, 95% CI = 4.59-25.89, p < 0.05). All the included studies were of moderate-to-high quality. TSA and sensitivity analyses suggested the robustness of this outcome. CONCLUSION: This systematic review demonstrated a certain correlation between HSPM and MIH, suggesting that HSPM can play a predictive role in the occurrence of MIH. Further high-quality, multicenter, and large-sample longitudinal studies are highly recommended.

Association of Toll-Like Receptor 7 (TLR7) Polymorphisms with Predisposition to Systemic Lupus Erythematosus (SLE): A Meta and Trial Sequential Analysis.

Systemic Lupus Erythematosus (SLE) is an autoimmune disorder characterized by autoantibody production and organ involvement. The role of toll-like receptor-7 in SLE is well established. Although genetic variations in the TLR-7 gene have been associated with an increased risk of developing SLE, the findings are not consistent. We performed a meta-analysis of previously published articles on four important single nucleotide polymorphisms in the TLR-7 gene (rs3853839, rs179008, rs179019, and rs179010) to reach a valid conclusion. Various literature databases, including PubMed, Science Direct, and Scopus, were scoured for eligible reports until May 10, 2023. GPower software v.3 was used to assess the power of individual reports included in the meta-analysis. Comprehensive Meta-analysis v3 software was used to perform all statistics. The publication biases in each genetic comparison model were investigated using funnel plots and Egger's regression test. To test heterogeneity, Cochrane Q statistics, probability value and I2 were used. Considering the predefined inclusion and exclusion criteria, the current study included a total of 10 eligible studies that included 15,472 SLE cases and 16,721 healthy controls. The meta-analysis revealed a significant association between TLR7 polymorphisms (rs179019 and rs179010) and susceptibility to SLE development. Other TLR7 polymorphisms (rs3853839 and rs179008), on the other hand, showed no significant association. Furthermore, the trial sequential analysis identified the need for additional case control studies for TLR-7 polymorphisms (rs3853839, rs179008, and rs179019) other than the rs179010 polymorphism. TLR7 variants for rs179010 and rs179019 are risk factor for the development of SLE. Further investigations are required to reach a valid conclusion.

Association of Four VEGFA Gene Variants with Rheumatoid Arthritis Risk: A Meta-analysis and Trial Sequential Analysis.

The association between rheumatoid arthritis (RA) risk and specific variants of the Vascular Endothelial Growth Factor A (VEGFA) gene remains contentious. This study sought to elucidate the correlations between RA risk and several VEGFA gene variants, including VEGFA-634 (rs2010963), VEGFA-C936 (rs3025039), VEGFA-2578 (rs699947), VEGFA-1154 (rs1570360), through a comprehensive meta-analysis. We systematically reviewed literature from the Cochrane Library database, Embase, PubMed, Web of Science, China National Knowledge Infrastructure, and the Wanfang Data Information Service platform to gather relevant case-control studies. Using odds ratio (OR) and 95% confidence interval (95% CI), we analyzed the data to assess potential correlations. Sensitivity analysis and the Egger's test were employed to ensure the results stability and to evaluate potential publication bias. Additionally, trial sequential analysis (TSA) was conducted to validate the findings. Our meta-analysis incorporated ten studies involving 2817 patients and 2855 controls. Results indicated that the AA genotype of VEGFA-1154 (rs1570360) is associated with a reduced risk of RA in the overall population (AG + GG vs AA: P = 0.032 OR = 1.932 95% CI 1.059-3.523). However, no significant association is found for VEGFA-634 (rs2010963), VEGFA-C936 (rs3025039), and VEGFA-2578 (rs699947) variants with RA risk. Subgroup analysis revealed a significant association between the VEGF rs3025039(C936) variant and RA risk in the PCR-RFLP group under the TC vs. CC model. TSA confirmed the sufficiency of the sample size for robust conclusions. These findings suggest that the G allele of VEGFA-1154 (rs1570360) may increase RA risk, whereas the A allele appears to confer a protective effect. This study enhances our understanding of the genetic predispositions to RA and underscores the potential role of VEGFA gene variants in its pathogenesis.

Superiority of kinematic alignment over mechanical alignment in total knee arthroplasty during medium- to long-term follow-up: A meta-analysis and trial sequential analysis.

PURPOSE: To compare and determine the reliability and conclusiveness of the medium- and long-term efficacy in terms of patient-reported outcome measures and the risk of revisions or reoperations (RRRs) of kinematic alignment (KA) and mechanical alignment (MA) in total knee arthroplasty. METHODS: A comprehensive search was conducted in Medline, EMBASE, Web of Science and Cochrane Database Library to identify relevant literature. Only randomised clinical trials (RCTs) published before July 2023 were included. The Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), Oxford Knee Score (OKS), Forgotten Joint Score (FJS) and RRR were compared. Additionally, OKS and RRR were subjected to a trial sequential analysis. RESULTS: Seven RCTs involving 572 knees were identified. The pooled analysis of the included studies demonstrated that KA showed better medium-term WOMAC and OKS (mean difference [MD] = -6.3, 95% confidence interval [CI]: -9.52 to -2.99, p < 0.05 and MD = 1.1, 95% CI: 0.05-2.15, p < 0.05), respectively), but no significant differences were observed in the long-term follow-up (MD = 2.1, 95% CI: -3.21 to 7.31, not significant [n.s.] and MD = 0.01, 95% CI: -2.43 to 2.46, n.s., respectively). FJS (standardised MD = -0.03, 95% CI: -0.25 to 0.19, n.s.) and RRR (risk ratio = 1.0, 95% CI: 0.57 to 1.74, n.s.) showed no significant intergroup differences (n.s.). The evidence quality ranged from moderate to high, and the trial sequential analysis indicated the need for additional high-quality RCTs to draw more conclusive results. CONCLUSIONS: KA showed better medium-term WOMAC and OKS, while KA and MA had similar FJS without increasing the RRR in medium- and long-term follow-up. Further research is needed for more conclusive results. LEVEL OF EVIDENCE: Level II (meta-analyses).

Is EIT-guided positive end-expiratory pressure titration for optimizing PEEP in ARDS the white elephant in the room? A systematic review with meta-analysis and trial sequential analysis.

Electrical Impedance Tomography (EIT) is a novel real-time lung imaging technology for personalized ventilation adjustments, indicating promising results in animals and humans. The present study aimed to assess its clinical utility for improved ventilation and oxygenation compared to traditional protocols. Comprehensive electronic database screening was done until 30th November, 2023. Randomized controlled trials, controlled clinical trials, comparative cohort studies, and assessments of EIT-guided PEEP titration and conventional methods in adult ARDS patients regarding outcome, ventilatory parameters, and P/F ratio were included. Our search retrieved five controlled cohort studies and two RCTs with 515 patients and overall reduced risk of mortality [RR = 0.68; 95% CI: 0.49 to 0.95; I2 = 0%], better dynamic compliance [MD = 3.46; 95% CI: 1.59 to 5.34; I2 = 0%] with no significant difference in PaO2/FiO2 ratio [MD = 6.5; 95%CI -13.86 to 26.76; I2 = 74%]. The required information size except PaO2/FiO2 was achieved for a power of 95% based on the 50% reduction in risk of mortality, 10% improved compliance as the cumulative Z-score of the said outcomes crossed the alpha spending boundary and did not dip below the inner wedge of futility. EIT-guided individualized PEEP titration is a novel modality; further well-designed studies are needed to substantiate its utility.

Further Studies are Needed for Testing the Effects of Topical Conditioned Medium of Stem Cells in Facial Skin Nonsurgical Resurfacing Modalities for Antiaging.

We would like to respond to the commentary with further understanding of the issue of potential statistical power in the analysis of our original finding. This further analysis has been planned to be carried out using the data from the wrinkle outcome because it has been contributed by the largest sample size with a dramatic effect size among all outcomes. Sequential analysis in this letter has been down with alpha 0.05 (type I error) and power of 0.80 (1-type II error) based on the O'Brien Fleming method. In addition to the common settings abovementioned, we chose a small effect size (SMD = 0.2) for avoiding underestimation in the optimal information size calculation and power analysis. The analysis was conducted using R via RStudio. The figure of sequential analysis shows that the cumulative effect of topical CM of stem cells on wrinkle outcome reaches statistical significance (z score of the end of blue line > 2), which is consistent with our original finding. Nevertheless, the information size of the outcome is insufficient (n = 118), which is lower than the required sample size (n = 1419). The observed power of the effects of topical CM of stem cells on the wrinkle outcome is only about 0.64, which is lower than the pre-defined or expected power of 0.80. Based on the fraction of information, although the observed z score of 3.232 for the cumulative effect surpasses 2, it does not surpass the monitoring boundary of 6.795 at the fraction (8.3%).Level of Evidence V This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Trial sequential analysis: A simple guide for judging the conclusiveness of the effect.

Meta-analysis is a statistical method used in systematic reviews to provide a quantitative estimate of the effect. However, including very few studies and participants may increase the risk of spurious findings. Trial sequential analysis (TSA) has been introduced to enhance the robustness of meta-analysis. TSA is a cumulative meta-analysis method that weighs type I and II errors while estimating the effect. The application of TSA can lead to a more accurate estimation of the clinical effectiveness of the intervention. The aim of the present paper was to introduce the TSA to orthodontic clinicians and researchers using continuous data from an orthodontic systematic review.

Relationship between CCL2 gene 2518A/G (rs1024611) polymorphism and age-related macular degeneration susceptibility: meta-analysis and trial sequential analysis.

PURPOSE: This study aimed to investigate the association between the CC-cytokine ligand-2 (CCL2) 2518A/G (rs1024611) single nucleotide polymorphism (SNP) and susceptibility to age-related macular degeneration (AMD). METHODS: PubMed, Embase, Web of Science, and other databases were searched for articles published before August 24, 2023. After searching, data extraction, and quality assessment, meta-analysis and trial sequential analysis were conducted using RevMan 5.4, Stata 17.0, and TSA 0.9.5.10 Beta software. Combined OR, P values, and 95% confidence intervals (CIs) were calculated. Sensitivity analysis, subgroup analysis and publication bias assessment were also performed. RESULTS: Six articles, comprising 1186 cases and 1124 controls, were included. No significant statistical difference was found in six main outcomes. However, due to observed heterogeneity and high sensitivity, subgroup analysis was performed, revealing statistically significant differences across different regions. No significant publication bias was observed. Trial sequential analysis suggested the need for additional follow-up case-control studies to further validate the findings. CONCLUSION: The CCL2 gene 2518A/G (rs1024611) polymorphism is associated with AMD susceptibility. Among Caucasian populations in West Asia and Europe, the G allele is protective against AMD, whereas in East and South Asia, it poses a risk factor.

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

Vitamin D receptor (VDR) is one of the most widely studied genes for the Tuberculosis (TB) susceptibility. Several studies have been conducted to establish some association between them but most of the time they are contradictory and underpowered. So, a trial sequential meta-analysis between VDR gene polymorphisms and TB susceptibility can provide a better understanding of the relationship. A meta-analysis was carried out using a total of 17 case-control studies which includes Fok1 (14 Studies), Bsm1 (8 Studies), Apa1 (8 Studies) and Taq1 (12 Studies) polymorphisms in the VDR gene searched from Pubmed and Google Scholar. Pooled Odds Ratio (OR) and 95% Confidence Interval (CI) were calculated using StatsDirect Version 3, using random effects model. Trial sequential analysis (TSA) was also performed to assess if the statistical significance of the meta-analysis was within monitoring boundaries. It was found that the individuals with BB genotype of Bsm1 polymorphism with OR = 0.713 (95%CI = 0.521, 0.974; p value < 0.05) and FF genotype of Fok1 polymorphism with pooled OR = 0.716 (95%CI = 0.523, 0.979; p value < 0.05) had decreased incidence of TB. Also, the aa genotype of Apa1 gene polymorphism increases susceptibility to TB with pooled OR = 1.997 (95%CI = 1.121, 3.558; p value < 0.05). All these analyses reached the required information size through TSA analysis. No statistically significant result was found for Taq1 polymorphisms and TB susceptibility. VDR polymorphisms in Fok1 and Bsm1 played protective roles against development of TB infection, while Apa1 appeared to have a significant association to TB susceptibility. Supplementary Information: The online version contains supplementary material available at 10.1007/s12291-022-01091-3.

[Meta-analysis and trial sequential analysis of Tanreqing Injection in treatment of severe pneumonia in elderly].

This study aimed to systematically evaluate the effectiveness and safety of Tanreqing Injection in the treatment of severe pneumonia in the elderly. Eighteen randomized controlled trials(RCTs) involving 1 457 elderly patients with severe pneumonia were included in the study after conducting searches in both Chinese and English databases as well as clinical trial registration platforms. The quality of the included studies was assessed using the Cochrane risk of bias assessment tool. Meta-analysis were conducted using RevMan 5.4 and Stata 17 software, and trial sequential analysis(TSA) was performed using TSA 0.9.5.10 beta software. Meta-analysis results showed that compared with conventional western medicine treatment, Tanreqing Injection + conventional western medical significantly improved the clinical effectiveness in elderly patients with severe pneumonia(RR=1.26, 95%CI[1.20, 1.32], P<0.000 01), arterial oxygen partial pressure(SMD=6.23, 95%CI[3.29, 9.18], P<0.000 1), oxygenation index(SMD=11.72, 95%CI[4.41, 19.04], P=0.002), reduce procalcitonin(SMD=-6.16, 95%CI[-8.10,-4.21], P<0.000 01), C-reactive protein(SMD=-8.50, 95%CI[-11.05,-5.96], P<0.000 01), white blood cell count(SMD=-4.56, 95%CI[-5.73,-3.39], P<0.000 01), and shortened the duration of fever(SMD=-3.12, 95%CI[-4.61,-1.63], P<0.000 1), cough(SMD=-4.84, 95%CI[-6.90,-2.79], P<0.000 01), lung rales(SMD=-0.99, 95%CI[-1.54,-0.44], P=0.000 4), and mechanical ventilation time(SMD=-3.26, 95%CI[-5.03,-1.50], P=0.000 3), increase CD4~+ T-cell levels(SMD=6.73, 95%CI[5.23, 8.23], P<0.000 01) and CD8~+ T-cell levels(SMD=7.47, 95% CI[5.32, 9.61], P<0.000 01) with no significant adverse reactions. TSA confirmed the stability and reliability of the results related to clinical effectiveness. This study suggests that Tanreqing Injection, as a Chinese medicinal preparation, has a significant therapeutic effect and good safety profile in the treatment of severe pneumonia in elderly patients. Due to the limited quality of the included studies, high-quality RCT is still needed to provide evidence support for the above conclusions.