Effects of Ambient Air Pollution on Hemostasis and Inflammation

BACKGROUND: Air pollution has consistently been associated with increased morbidity and mortality due to respiratory and cardiovascular disease. Underlying biological mechanisms are not entirely clear, and hemostasis and inflammation are suggested to be involved. OBJECTIVES: Our aim was to study the association of the variation in local concentrations of airborne particulate matter (PM) with aerodynamic diameter < 10 mu m, carbon monoxide, nitrogen monoxide, nitrogen dioxide, and ozone with platelet aggregation, thrombin generation, fibrinogen, and C-reactive protein (CRP) levels in healthy individuals. METHODS: From 40 healthy volunteers, we collected 13 consecutive blood samples within a 1-year period and measured light-transmittance platelet aggregometry, thrombin generation, fibrinogen, and CRP. We performed regression analysis using generalized additive models to study the association between the hemostatic and inflammatory variables, and local environmental concentrations 0 air pollutants for time lags within 24 hr before blood sampling or 24-96 hr before blood sampling. RESULTS: In general, air pollutants were associated with platelet aggregation [average, +8% per interquartile range (IQR), p < 0.01] and thrombin generation (average, +1% per IQR, p < 0.015). Platelet aggregation was not affected by in vitro incubation of plasma with PM. We observed no relationship between any of the air pollutants and fibrinogen or CRP levels. CONCLUSIONS:. Air pollution increased platelet aggregation as well as coagulation activity but had no clear effect on systemic inflammation. These prothrombotic effects may partly explain the relationship between air pollution and the risk of ischemic cardiovascular disease

Search Filters for Finding Prognostic and Diagnostic Prediction Studies in Medline to Enhance Systematic Reviews

Background: The interest in prognostic reviews is increasing, but to properly review existing evidence an accurate search filer for finding prediction research is needed. The aim of this paper was to validate and update two previously introduced search filters for finding prediction research in Medline: the Ingui filter and the Haynes Broad filter. Methodology/Principal Findings: Based on a hand search of 6 general journals in 2008 we constructed two sets of papers. Set 1 consisted of prediction research papers (n = 71), and set 2 consisted of the remaining papers (n = 1133). Both search filters were validated in two ways, using diagnostic accuracy measures as performance measures. First, we compared studies in set 1 (reference) with studies retrieved by the search strategies as applied in Medline. Second, we compared studies from 4 published systematic reviews (reference) with studies retrieved by the search filter as applied in Medline. Next -using word frequency methods - we constructed an additional search string for finding prediction research. Both search filters were good in identifying clinical prediction models: sensitivity ranged from 0.94 to 1.0 using our hand search as reference, and 0.78 to 0.89 using the systematic reviews as reference. This latter performance measure even increased to around 0.95 (range 0.90 to 0.97) when either search filter was combined with the additional string that we developed. Retrieval rate of explorative prediction research was poor, both using our hand search or our systematic review as reference, and even combined with our additional search string: sensitivity ranged from 0.44 to 0.85. Conclusions/Significance: Explorative prediction research is difficult to find in Medline, using any of the currently available search filters. Yet, application of either the Ingui filter or the Haynes broad filter results in a very low number missed clinical prediction model studie

Prevention and management of adverse events of novel agents in multiple myeloma: a consensus of the European Myeloma Network

During the last few years, several new drugs have been introduced for treatment of patients with multiple myeloma, which have significantly improved the treatment outcome. All of these novel substances differ at least in part in their mode of action from similar drugs of the same drug class, or are representatives of new drug classes, and as such present with very specific side effect profiles. In this review, we summarize these adverse events, provide information on their prevention, and give practical guidance for monitoring of patients and for management of adverse events