De Baets F.,Universitair Ziekenhuis
Tijdschrift voor Geneeskunde
Respiratory symptoms (wheezing, a cough, bronchorrea, etc.) are common problems in preschool children. The physiopathology differs in many ways from asthma in older children, adolescents and adults. Allergy is a minor problem, the impact of inflammation and aspecific bronchial hyperresponsiveness has not yet been cleared. Viral infections, the airway diameter and the collapsibility seem to exert a major influence, explaining the natural course. The treatment should follow specific guidelines, relying on evidence-based research. Because of the specific physiopathology in many preschool children, the natural course is different from genuine asthma and relies partly on the growth of the bronchial system. Copyright © 2012, Kowsar Corp. Source
De Benedetti F.,Istituto di Ricovero e Cura rattere Scientifico Ospedale Pediatrico Bambino Gesu |
Brunner H.I.,Cincinnati Childrens Hospital Medical Center |
Ruperto N.,Paediatric Rheumatology International Trials Organisation Coordinating Center |
Kenwright A.,Hoffmann-La Roche |
And 22 more authors.
New England Journal of Medicine
BACKGROUND: Systemic juvenile idiopathic arthritis (JIA) is the most severe subtype of JIA; treatment options are limited. Interleukin-6 plays a pathogenic role in systemic JIA. METHODS: We randomly assigned 112 children, 2 to 17 years of age, with active systemic JIA (duration of ≥6 months and inadequate responses to nonsteroidal antiinflammatory drugs and glucocorticoids) to the anti-interleukin-6 receptor antibody tocilizumab (at a dose of 8 mg per kilogram of body weight if the weight was ≥30 kg or 12 mg per kilogram if the weight was <30 kg) or placebo given intravenously every 2 weeks during the 12-week, double-blind phase. Patients meeting the predefined criteria for nonresponse were offered open-label tocilizumab. All patients could enter an open-label extension. RESULTS: At week 12, the primary end point (an absence of fever and an improvement of 30% or more on at least three of the six variables in the American College of Rheumatology [ACR] core set for JIA, with no more than one variable worsening by more than 30%) was met in significantly more patients in the tocilizumab group than in the placebo group (64 of 75 [85%] vs. 9 of 37 [24%], P<0.001). At week 52, 80% of the patients who received tocilizumab had at least 70% improvement with no fever, including 59% who had 90% improvement; in addition, 48% of the patients had no joints with active arthritis, and 52% had discontinued oral glucocorticoids. In the double-blind phase, 159 adverse events, including 60 infections (2 serious), occurred in the tocilizumab group, as compared with 38, including 15 infections, in the placebo group. In the double-blind and extension periods combined, 39 serious adverse events (0.25 per patient-year), including 18 serious infections (0.11 per patient-year), occurred in patients who received tocilizumab. Neutropenia developed in 19 patients (17 patients with grade 3 and 2 patients with grade 4), and 21 had aminotransferase levels that were more than 2.5 times the upper limit of the normal range. CONCLUSIONS: Tocilizumab was efficacious in severe, persistent systemic JIA. Adverse events were common and included infection, neutropenia, and increased aminotransferase levels. (Funded by Hoffmann-La Roche; ClinicalTrials.gov number, NCT00642460.) Copyright © 2012 Massachusetts Medical Society. Source
Thibault F.,University Pierre and Marie Curie |
Dromain C.,Institute Of Cancerologie Gustave Roussy |
Breucq C.,Universitair Ziekenhuis |
Balleyguier C.S.,Institute Of Cancerologie Gustave Roussy |
And 5 more authors.
Objectives: To compare the diagnostic performance of single-view breast tomosynthesis (BT) with that of dual-view mammography (MX); to assess the benefit of adding the craniocaudal (CC) mammographic view to BT, and of adding BT to MX plus breast ultrasound, considered to be the reference work-up. Methods: One hundred and fifty-five consenting patients with unresolved mammographic and/or ultrasound findings or breast symptoms underwent conventional work-up plus mediolateral oblique-view BT of the affected breast. The final study set in 130 patients resulted in 55 malignant and 76 benign and normal cases. Seven breast radiologists rated the cases through five sequential techniques using a BIRADS-based scale: MX, MX + ultrasound, MX + ultrasound + BT, BT, BT + MX(CC). Multireader, multicase receiver operating characteristic (ROC) analysis was performed and performance of the techniques was assessed from the areas under ROC curves. The performance of BT and of BT + MX(CC) was tested versus MX; the performance of MX + ultrasound + BT tested versus MX + ultrasound. Results: Tomosynthesis was found to be non-inferior to mammography. BT + MX(CC) did not appear to be superior to MX, and MX + ultrasound + BT not superior to MX + ultrasound. Conclusions: Overall, none of the five techniques tested outperformed the others. Further clinical studies are needed to clarify the role of BT as a substitute for traditional work-up in the diagnostic environment. Key Points: • Digital breast tomosynthesis is a new adjunct to mammography and breast ultrasound. • We compared the diagnostic performance of these investigations in an experimental observer study. • Single-view breast tomosynthesis was confirmed as non-inferior to dual-view mammography. • None of the investigations (or combinations) tested outperformed the others. • Further prospective studies are needed to clarify precise role of tomosynthesis for diagnostic application. © 2013 European Society of Radiology. Source
Harton G.L.,Reprogenetics LLC |
Harton G.L.,Genetics and IVF Institute |
De Rycke M.,Universitair Ziekenhuis |
Fiorentino F.,Genoma Laboratories |
And 5 more authors.
In 2005, the European Society for Human Reproduction and Embryology (ESHRE) PGD Consortium published a set of Guidelines for Best Practice PGD to give information, support and guidance to potential, existing and fledgling PGD programmes. The subsequent years have seen the introduction of a number of new technologies as well as the evolution of current techniques. Additionally, in light of recent advice from ESHRE on how practice guidelines should be written and formulated, the Consortium believed it was timely to revise and update the PGD guidelines. Rather than one document that covers all of PGD, as in the original publication, these guidelines are separated into four new documents that apply to different aspects of a PGD programme, i.e. Organization of a PGD centre, fluorescence in situ hybridization-based testing, Amplification-based testing and Polar Body and Embryo Biopsy for PGD/preimplantation genetic screening. Here, we have updated the sections that pertain to amplification-based PGD. Topics covered in this guideline include inclusion/exclusion criteria for amplification-based PGD testing, preclinical validation of tests, amplification-based testing methods, tubing of cells for analysis, set-up of local IVF centre and Transport PGD centres, quality control/quality assurance and diagnostic confirmation of untransferred embryos. © 2010 The Author. Source
Wolchok J.D.,Sloan Kettering Cancer Center |
Neyns B.,Universitair Ziekenhuis |
Linette G.,University of Washington |
Negrier S.,Center Leon Berard |
And 12 more authors.
The Lancet Oncology
Background: Ipilimumab is a human monoclonal antibody that blocks cytotoxic T-lymphocyte antigen 4 and has shown promising activity in advanced melanoma. We aimed to ascertain the antitumour efficacy of ipilimumab in patients with advanced melanoma. Methods: We undertook a randomised, double-blind, phase 2 trial in 66 centres from 12 countries. 217 patients with previously treated stage III (unresectable) or stage IV melanoma were randomly assigned a fixed dose of ipilimumab of either 10 mg/kg (n=73), 3 mg/kg (n=72), or 0·3 mg/kg (n=72) every 3 weeks for four cycles (induction) followed by maintenance therapy every 3 months. Randomisation was done with a permuted block procedure, stratified on the basis of type of previous treatment. The primary endpoint was best overall response rate (the proportion of patients with a complete or partial response, according to modified WHO criteria). Efficacy analyses were done by intention to treat, whereas safety analyses included patients who received at least one dose of ipilimumab. This study is registered with ClinicalTrials.gov, number NCT00289640. Findings: The best overall response rate was 11·1% (95% CI 4·9-20·7) for 10 mg/kg, 4·2% (0·9-11·7) for 3 mg/kg, and 0% (0·0-4·9) for 0·3 mg/kg (p=0·0015; trend test). Immune-related adverse events of any grade arose in 50 of 71, 46 of 71, and 19 of 72 patients at doses of 10 mg/kg, 3 mg/kg, and 0·3 mg/kg, respectively; the most common grade 3-4 adverse events were gastrointestinal immune-related events (11 in the 10 mg/kg group, two in the 3 mg/kg group, none in the 0·3 mg/kg group) and diarrhoea (ten in the 10 mg/kg group, one in the 3 mg/kg group, none in the 0·3 mg/kg group). Interpretation: Ipilimumab elicited a dose-dependent effect on efficacy and safety measures in pretreated patients with advanced melanoma, lending support to further studies at a dose of 10 mg/kg. Funding: Bristol-Myers Squibb. © 2010 Elsevier Ltd. All rights reserved. Source