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OBJECTIVES Randomized clinical trials provide the best evidence of treatment effectiveness; factors determining their impact are unknown. We sought to determine the influence of funding (industry vs nonindustry), research (comparative effectiveness vs technology evaluation), and organizational models (investigator-led trials group vs others) on the impact of large trials in critical care medicine. DATA SOURCES We searched MEDLINE for randomized clinical trials published between 1990 and 2012 in five critical care, five general interest, and one pediatrics journal. Impact was evaluated as annual citation rates measured using the ISI Web of Knowledge database. STUDY SELECTION Eligible trials enrolled at least 100 critically ill adults, children, or neonates, evaluated an intervention that was applied during the ICU stay, and reported mortality and/or length of ICU or hospital stay. DATA EXTRACTION Two reviewers identified eligible studies, and two separate reviewers extracted data. DATA SYNTHESIS We identified 391 randomized clinical trials, recruiting 208,154 subjects. Funding source--industry versus peer review versus mixed--did not impact citation rates. Comparative effectiveness studies made up 52.5% of the reports and were cited more frequently than studies evaluating novel technologies (median, 15.6 vs 10.3 citations/yr; p = 0.002). Trials conducted by investigator-led trials groups (n = 45) were cited a median of 45.7 (interquartile range [IQR], 17.3-86.2) times per year, significantly more often (p < 0.0001) than multicenter trials conducted by ad hoc groups (n = 89; median, 19 [IQR, 8.7-30.4]) or industry (n = 85; median, 12.3 [IQR, 5.4-24.1]), and more than single-center trials (n = 116; median, 6.8 [IQR, 3.5-12.8]) or small ad hoc trials involving two to five centers (n = 59; median, 11.0 [IQR, 4.5-22.4]). Although only 11.5% of all trials included, randomized clinical trials from investigator-led research consortia accounted for nine of the 16 studies cited more than 100 times per year and 23.4% of all citations; their costs were substantially less than the typical costs of industry-run trials.. CONCLUSIONS Clinical trials conducted by investigator-led research groups are significantly more frequently cited than industry-led trials in critical care medicine. In addition, costs appear to be substantially lower with investigator-led trials. Support for and expansion of this model of research can ensure that critical care research is clinically relevant and practice changing.

Background: Graft Imaging to Improve Patency (GRIIP), a single-center, randomized blinded clinical trial, reported that intraoperative graft assessment with graft revision according to a priori criteria of transit time flowmetry (TTF) and intraoperative fluorescent angiography did not improve graft patency at one year after coronary artery bypass grafting (CABG) when compared with standard intraoperative management. The objective of this study is to investigate whether other TTF values are more predictive of the saphenous vein graft (SVG) failure and/or clinical outcomes. Methods: This is a case control retrospective study of 65 SVGs from 44 patients from GRIIP. Study outcomes were graft patency at 12 months and major adverse cardiac events (MACE; death, myocardial infarction, repeat revascularization). Results: Twenty-two SVGs were occluded. In receiver operating characteristic curve analysis, TTF mean flow was significantly predictive of one-year SVG failure (area under the curve = 0.698, p

Granulocyte-macrophage colony-stimulating factor (GM-CSF) and the related cytokines interleukin (IL)-3 and IL-5 regulate the production and functional activation of hematopoietic cells. GM-CSF acts on monocytes/macrophages and granulocytes, and several chronic inflammatory diseases and a number of haematological malignancies such as Juvenile myelomonocytic leukaemia (JMML) are associated with deregulated GM-CSF receptor (GMR) signaling. The downregulation of GMR downstream signaling is mediated in part by the clearance of activated GMR via the proteasome, which is dependent on the ubiquitylation of βc signaling subunit of GMR via an unknown E3 ubiquitin ligase. Here, we show that suppressor of cytokine signaling 1 (SOCS-1), best known for its ability to promote ubiquitin-mediated degradation of the non-receptor tyrosine kinase Janus kinase 2 (JAK2), also targets GMRβc for ubiquitin-mediated degradation and attenuates GM-CSF-induced downstream signaling.