This review summarizes the present status of physiologically based pharmacokinetic (PBPK) modeling and simulation (M&S) and its application in support of pediatric drug research. We address the reasons that PBPK is suited to the current needs of pediatric drug development and pharmacotherapy in light of the evolution in pediatric PBPK methodologies and approaches, which were originally developed for the purpose of toxicologic evaluation. Also discussed is the current degree of confidence in using PBPK to support pediatric drug development and registration and the key factors essential for robust results and broader adoption of pediatric PBPK M&S.

The aim of this study was to develop a simplified ultrasound scanning procedure and scoring method, named Haemophilia Early Arthropathy Detection with UltraSound [HEAD-US], to evaluate joints of patients with haemophilic arthropathy. After an initial consensus-based process involving a multidisciplinary panel of experts, three comprehensive and evidence-based US scanning procedures to image the elbow, knee and ankle were established with the aim to increase sensitivity in detection of early signs of joint involvement while keeping the technique easy and quick to perform. Each procedure included systematic evaluation of synovial recesses and selection of a single osteochondral surface for damage analysis. Based on expert consensus, a simplified scoring system based on an additive scale was created to define the joint status and, in perspective, to offer a tool to evaluate disease progression and monitor the result of treatment in follow-up studies.

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There is not agreement about the best maintenance treatment for patients with diffuse lupus nephritis. This multicenter, randomized trial compared the safety and efficacy of cyclosporine and azathioprine. Seventy-five patients with diffuse proliferative lupus were given three intravenous methylprednisolone pulses followed by prednisone and oral cyclophosphamide for a median of 90 d. Subsequently, patients were randomly assigned either to cyclosporine or to azathioprine for 2 yr (core study). Treatment continued for up to 4 yr (follow-up study). The primary outcome measure was the incidence of disease flares. Secondary end points were proteinuria per day, creatinine clearance, and adverse effects. Seven flares occurred in the cyclosporine group, and eight occurred in the azathioprine group. At the end of the core study, mean proteinuria decreased from 2.