Intravenous immunoglobulin vs observation in childhood immune thrombocytopenia: a randomized controlled trial.

Management of children with newly diagnosed immune thrombocytopenia (ITP) consists of careful observation or immunomodulatory treatment. Observational studies suggest a lower risk for chronic ITP in children after intravenous immunoglobulin (IVIg) treatment. In this multicenter randomized trial, children aged 3 months to 16 years with newly diagnosed ITP, platelet counts 20 × 109/L or less, and mild to moderate bleeding were randomly assigned to receive either a single infusion of 0.8 g/kg IVIg or careful observation. Primary outcome was development of chronic ITP, which at the time of study initiation was defined as a platelet count lower than 150 × 109/L after 6 months. Two hundred six children were allocated to receive IVIg (n = 102) or careful observation (n = 104). Chronic ITP occurred in 18.6% of the patients in the IVIg group and 28.9% in the observation group (relative risk [RR], 0.64; 95% confidence interval [CI], 0.38-1.08). Platelet counts lower than 100 × 109/L at 12 months (current definition of chronic ITP) were observed in 10% of children in the IVIg group and 12% in the observation group (RR, 0.83; 95% CI, 0.38-1.84). Complete response rates in the first 3 months were significantly higher in the IVIg group. Immunoglobulin G Fc receptor IIb genetic variations were associated with early complete response in both groups. Grade 4 to 5 bleeding occurred in 9% of the patients in the observation group vs 1% in the IVIg group. This trial was registered at www.trialregister.nl as NTR 1563.

A boy with a tight skin: Borrelia-associated early-onset morphea.

We present a case of a 16-year-old boy with morphea caused by Borrelia burgdorferi. We re-emphasise an immunohistochemical method, focus floating microscopy (FFM), to detect Borrelia burgdorferi spirochetes in tissue sections. Focus floating microscopy (FFM) proved to be more sensitive than polymerase chain reaction (PCR) and nearly equally specific.

Sequential design with boundaries approach in pediatric intervention research reduces sample size.

OBJECTIVE: To estimate the difference between the number of subjects actually included in pediatric sequential trials and the sample size that would have been included with a fixed-sample design. STUDY DESIGN AND SETTING: A systematic review of pediatric sequential trials was performed. Methodological quality was assessed using a criteria list based on the CONSORT (Consolidated Standards of Reporting Trials) statement, and data were extracted by two reviewers independently. Where possible, fixed sample size calculations were performed using the same assumptions as those of the sequential design, and compared with the reported number of included patients. RESULTS: Twenty-four sequential trials, published between 1963 and 2005, were found. In nine studies, the information about the assumptions was sufficient to calculate a fixed sample size. The median reduction in included sample size in these trials compared with the fixed sample size calculation was 52 subjects (range: -22 to 229), a reduction of 35% (range: -42% to 90%) of the fixed sample size. The median sample size reduction when considering the number of subjects included in the analysis until crossing of the boundaries was 77% (range: 15-90%). CONCLUSION: Sequential design is a useful method for optimizing the sample size in pediatric clinical trials and may lead to substantial sample size reductions.

Pitfalls in the design and analysis of paediatric clinical trials: a case of a 'failed' multi-centre study, and potential solutions.

AIM: To increase awareness of possible pitfalls in the design and analysis of a multi-centre randomized clinical trial and to give an overview of alternative study designs and their consequences for power analyses in case of limited availability of trial participants. METHODS: Investigation of the assumptions in the power calculation and re-analysis of the original data of a 'failed' trial on the effect of dexamethasone on the duration of mechanical ventilation in young children with respiratory syncytial virus infection. Use of 'boundaries approach' is explored using the data from this trial. A comprehensive overview of the various modern solutions for the design of a subsequent trial in this field is given. RESULTS: Two frequent major deficiencies of trial design and data analysis are reviewed in depth, i.e. too optimistic assumptions for the sample size calculation and failure to adjust for centre effects. CONCLUSION: Critical review of trial assumptions and if necessary sample size recalculation based on an internal pilot by a data monitoring committee is recommended to maximize the probability of obtaining conclusive results.

Adherence to a guideline for coumarins in pregnancy.

OBJECTIVE: To asses the adherence in daily clinical practice to a guideline for anticoagulation during pregnancy. METHODS: The Dutch anticoagulation clinics developed a pregnancy guideline for anticoagulant therapy in order to avoid foetal exposure to coumarins between the 6th and 9th week of gestation. Anticoagulation was studied in 282 prospectively-registered pregnant women, who were treated by 26 different anticoagulation clinics. RESULTS: The guideline was adhered to in 93% of treated women. Conforming to the guideline, the majority of patients commenced anticoagulation with heparin in the first trimester (n = 81) or started treatment from the second trimester onwards (n = 168). At the time of conception, 31 anticoagulated women were on coumarin treatment. In 13 of these patients (42%), coumarins were withdrawn before the 6th gestational week. In two pregnant women coumarin therapy started unintentionally during the first trimester of gestation. CONCLUSION: The present study shows that the guideline under study is useful in daily clinical practice. A careful instruction of women of child-bearing age who need medication remains important.