The interpretation of systematic reviews with meta-analyses: an objective or subjective process?

<p>Abstract</p> <p>Background</p> <p>Discrepancies between the conclusions of different meta-analyses (quantitative syntheses of systematic reviews) are often ascribed to methodological differences. The objective of this study was to determine the discordance in interpretations when meta-analysts are presented with identical data.</p> <p>Methods</p> <p>We searched the literature for all randomized clinical trials (RCT) and review articles on the efficacy of intravenous magnesium in the early post-myocardial infarction period. We organized the articles chronologically and grouped them in packages. The first package included the first RCT, and a summary of the review articles published prior to first RCT. The second package contained the second and third RCT, a meta-analysis based on the data, and a summary of all review articles published prior to the third RCT. Similar packages were created for the 5^thRCT, 10^thRCT, 20^thRCT and 23^rdRCT (all articles). We presented the packages one at a time to eight different reviewers and asked them to answer three clinical questions after each package based solely on the information provided. The clinical questions included whether 1) they believed magnesium is now proven beneficial, 2) they believed magnesium will eventually be proven to be beneficial, and 3) they would recommend its use at this time.</p> <p>Results</p> <p>There was considerable disagreement among the reviewers for each package, and for each question. The discrepancies increased when the heterogeneity of the data increased. In addition, some reviewers became more sceptical of the effectiveness of magnesium over time, and some reviewers became less sceptical.</p> <p>Conclusion</p> <p>The interpretation of the results of systematic reviews with meta-analyses includes a subjective component that can lead to discordant conclusions that are independent of the methodology used to obtain or analyse the data.</p

Effect of Cytoskeletal Disruption on Mechanotransduction of Hydrostatic Pressure by C3H10T1/2 Murine Fibroblasts

Cyclic hydrostatic pressure of physiological magnitude (< 10 MPa) stimulates chondrogenic differentiation of mesenchymal stem cells, but mechanotransduction mechanisms are not well understood. It was hypothesized that an intact cytoskeleton would be required for uninhibited mechanotransduction of hydrostatic pressure. Therefore we examined the effects of drugs which selectively interfere with actin and tubulin polymerization on pressure-induced upregulation of aggrecan and col2a1 (type II collagen) mRNA expression. C3H10T1/2 cells were cultured as pellets in either 4µM cytochalasin D or 4µM nocodazole and subjected to 3 days of cyclic hydrostatic compression (1 Hz, 5 MPa, 2 h per day). Phalloidin staining and indirect immunostaining with anti α-tubulin antibody confirmed disruption of microfilament and microtubule assemblies, respectively. Real time RT-PCR revealed that both drugs substantially lowered the basal level of aggrecan and col2a1 mRNA, but that neither drug prevented a pressure-stimulated increase in gene expression relative to the altered basal state. Thus upregulation of macromolecular gene expression by cyclic hydrostatic pressure did not require a completely intact cytoskeleton