ABSTRACT

The number of meta-analyses of aggregate data has dramatically increased due to the facility of obtaining data from publications and the development of free, easy-to-use, and specialised statistical software. Even when meta-analyses include the same studies, their results may vary owing to different methodological choices. Assessment of the replication of meta-analysis provides an example of the variation of effect 'naturally' observed between multiple research projects. Reproducibility of results has mostly been reported using graphical descriptive representations. A quantitative analysis of such results would enable (i) breakdown of the total observed variability with quantification of the variability generated by the replication process and (ii) identification of which variables account for this variability, such as methodological quality or the statistical analysis procedures used. These variables might explain systematic mean differences between results and dispersion of the results. To quantitatively characterise the reproducibility of meta-analysis results, a bivariate linear mixed-effects model was developed to simulate both mean results and their corresponding uncertainty. Results were assigned to several replication groups, those assessing the same studies, outcomes, treatment indication and comparisons classified in the same replication group. A nested random effect structure was used to break down the total variability within each replication group and between these groups to enable calculation of an intragroup correlation coefficient and quantification of reproducibility. Determinants of variability were investigated by modelling both mean and variance parameters using covariates. The proposed model was applied to the example of meta-analyses evaluating direct oral anticoagulants in the acute treatment of venous thromboembolism.

PMID:37846195 | DOI:10.1002/jrsm.1676

20:12

PubMed articles on: Cancer & VTE/PE

Associations Between Immune-Related Venous Thromboembolism and Efficacy of Immune Checkpoint Inhibitors: A Systematic Review and Meta-Analysis

Clin Appl Thromb Hemost. 2023 Jan-Dec;29:10760296231206799. doi: 10.1177/10760296231206799.

ABSTRACT

This study aims to summarize the available data and determine if the presence of venous thromboembolism (VTE) immune-related adverse event (irAE) in patients with immune checkpoint inhibitor (ICI) therapy is associated with improved treatment efficacy and clinical outcomes, which in turn was used to help optimize patient selection for anticoagulation therapy and inform rational treatment strategies for overcoming the mechanisms of ICI resistance. PubMed, Embase, Web of Science, and Cochrane Library were searched up to March 18, 2023, for studies assessing the relationship between VTE irAE development during ICI therapy and cancer outcomes. Seven primary articles with a total of 4437 patients were included in the overall survival (OS) meta-analysis. Patients with VTE had a significant increase in overall mortality compared to patients without VTE in adjusted hazard ratios (HRs 1.36, 95% confidence interval [CI] 1.06-1.75, P = .02). In the studies where immortal time bias (ITB) was accounted for, patients with VTE irAE also had poor OS than those without. HR and the corresponding 95% CI values in the non-ITB group were 2.53 (1.75-3.66, P < .00001) with low heterogeneity (P = .17, I2 = 48%) and 1.21 (1.06-1.37, P = .004) in the ITB group with no heterogeneity (P = .95, I2 = 0%), respectively. Despite the heterogeneity identified, the evidence does suggest that VTE irAE occurrence could be served as a prognostic indicator, with higher frequencies of occurrence associated with poorer OS. However, the fundamental role of this association with clinical consequences should be further investigated in large cohorts and clinical trials.

PMID:37844585 | PMC:PMC10586005 | DOI:10.1177/10760296231206799

20:13

PubMed articles on: Cancer & VTE/PE

Pulmonary Embolism Treatment Evolution: A Comparative Analysis of Pulmonary Embolism Response Team Management at a Single Institution

Am J Cardiol. 2023 Oct 14;208:171-172. doi: 10.1016/j.amjcard.2023.09.003. Online ahead of print.

NO ABSTRACT

PMID:37844520 | DOI:10.1016/j.amjcard.2023.09.003

20:13

PubMed articles on: Cancer & VTE/PE

Causal effect of atrial fibrillation on pulmonary embolism: a mendelian randomization study

J Thromb Thrombolysis. 2023 Oct 15. doi: 10.1007/s11239-023-02903-w. Online ahead of print.

ABSTRACT

Atrial fibrillation (AF) can increase thrombosis, especially arterial thrombosis, and some studies show that AF patients have a higher risk of developing pulmonary embolism (PE). The objective of our study is to investigate whether there is a direct causal effect of AF on PE. A two-sample Mendelian randomization (MR) approach was utilized to determine whether there is a causal relationship between AF and PE. European population-based consortia provided statistical data on the associations between Single Nucleotide Polymorphisms (SNPs) and relevant traits. The AF dataset was obtained from genome-wide association studies (GWAS) comprising 60,620 cases and 970,216 controls, while a GWAS of 1846 cases and 461,164 controls identified genetic variations associated with PE. Estimation of the causal effect was mainly performed using the random effects inverse-variance weighted method (IVW). Additionally, other tests such as MR-Egger intercept, MR-PRESSO, Cochran's Q test, "Leave-one-out," and funnel plots were conducted to assess the extent of pleiotropy and heterogeneity. Using 70 SNPs, there was no evidence to suggest an association between genetically predicted AF and risk of PE with multiplicative random-effects IVW MR analysis (odds ratio = 1.0003, 95% confidence interval: 0.9998-1.0008, P = 0.20). A null association was also observed in other methods. MR-Egger regression and MR-PRESSO respectively showed no evidence of directional (intercept, - 2.25; P = 0.94) and horizontal(P-value in the global heterogeneity test = 0.99) pleiotropic effect across the genetic variants. No substantial evidence was found to support the causal role of AF in the development of PE. Causal effect of atrial fibrillation on pulmonary embolism: a Mendelian randomization study. AF atrial fibrillation, PE pulmonary embolism, GWAS genome-wide association studies, SNPs single nucleotide polymorphisms, OR odds ratio, CI confidence interval.

PMID:37839022 | DOI:10.1007/s11239-023-02903-w

20:13

PubMed articles on: Cancer & VTE/PE

Intensify Standardized Anticoagulation for Cancer-Associated Pulmonary Embolism: From Single-Center Real-World Data

Clin Ther. 2023 Oct 12:S0149-2918(23)00378-8. doi: 10.1016/j.clinthera.2023.09.014. Online ahead of print.