Amin S.B.,Dana-Farber Cancer Institute |
Yip W.-K.,Harvard University |
Minvielle S.,Hopital de Nantes |
Minvielle S.,University of Nantes |
And 18 more authors.
Leukemia | Year: 2014
With advent of several treatment options in multiple myeloma (MM), a selection of effective regimen has become an important issue. Use of gene expression profile (GEP) is considered an important tool in predicting outcome; however, it is unclear whether such genomic analysis alone can adequately predict therapeutic response. We evaluated the ability of GEP to predict complete response (CR) in MM. GEP from pretreatment MM cells from 136 uniformly treated MM patients with response data on an IFM, France led study were analyzed. To evaluate variability in predictive power due to microarray platform or treatment types, additional data sets from three different studies (n=511) were analyzed using same methods. We used several machine learning methods to derive a prediction model using training and test subsets of the original four data sets. Among all methods employed for GEP-based CR predictive capability, we got accuracy range of 56-78% in test data sets and no significant difference with regard to GEP platforms, treatment regimens or in newly diagnosed or relapsed patients. Importantly, permuted P-value showed no statistically significant CR predictive information in GEP data. This analysis suggests that GEP-based signature has limited power to predict CR in MM, highlighting the need to develop comprehensive predictive model using integrated genomics approach.Leukemia advance online publication, 24 June 2014; doi:10.1038/leu.2014.140.
Jabre P.,Assistance Publique Hopitaux de Paris AP HP |
Jabre P.,University of Paris Descartes |
Belpomme V.,APHP |
Azoulay E.,AP HP |
And 22 more authors.
New England Journal of Medicine | Year: 2013
Background: The effect of family presence during cardiopulmonary resuscitation (CPR) on the family members themselves and the medical team remains controversial. Methods: We enrolled 570 relatives of patients who were in cardiac arrest and were given CPR by 15 prehospital emergency medical service units. The units were randomly assigned either to systematically offer the family member the opportunity to observe CPR (intervention group) or to follow standard practice regarding family presence (control group). The primary end point was the proportion of relatives with posttraumatic stress disorder (PTSD)-related symptoms on day 90. Secondary end points included the presence of anxiety and depression symptoms and the effect of family presence on medical efforts at resuscitation, the well-being of the health care team, and the occurrence of medicolegal claims. Results: In the intervention group, 211 of 266 relatives (79%) witnessed CPR, as compared with 131 of 304 relatives (43%) in the control group. In the intention-to-treat analysis, the frequency of PTSD-related symptoms was significantly higher in the control group than in the intervention group (adjusted odds ratio, 1.7; 95% confidence interval [CI], 1.2 to 2.5; P = 0.004) and among family members who did not witness CPR than among those who did (adjusted odds ratio, 1.6; 95% CI, 1.1 to 2.5; P = 0.02). Relatives who did not witness CPR had symptoms of anxiety and depression more frequently than those who did witness CPR. Family-witnessed CPR did not affect resuscitation characteristics, patient survival, or the level of emotional stress in the medical team and did not result in medicolegal claims. Conclusions: Family presence during CPR was associated with positive results on psychological variables and did not interfere with medical efforts, increase stress in the health care team, or result in medicolegal conflicts. (Funded by Programme Hospitalier de Recherche Clinique 2008 of the French Ministry of Health; ClinicalTrials.gov number, NCT01009606). Copyright © 2013 Massachusetts Medical Society.
Raffi F.,Hopital de Nantes |
Wainberg M.A.,McGill University
Virologie | Year: 2013
Strand transfer inhibitors of HIV-1 integrase represent a new and very potent class of compounds, besides reverse transcriptase and protease inhibitors. The first integrase inhibitor, raltegravir, was made available in 2007. Recently, phase 3 studies of two new compounds - elvitegravir which needs pharmacological boosting with either ritonavir or cobicistat, and dolutegravir - have been presented, showing high virologic success rates, over 48-96 weeks, both in first-line antiretroviral therapy and in the treatment of experienced patients. The clinical tolerance of the three inhibitors is good, and they have globally a good safety profile. Dolutegravir and cobicistat exerts a blockade of the renal tubular secretion of creatinine, leading to a decrease in estimated creatinine clearance, which does not reflect renal toxicity, i.e. decrease in glomerular filtration. Both dolutegravir and elvitegravir (within the fixed dose combination of TDF/FTC/elvitegravir/cobicistat) should be available in clinical practice soon, which will offer more options for the strategic use of integrase inhibitors to treat both HIV-1 and possibly HIV-2 infections.