Early clinical trials of therapies to treat Duchenne muscular dystrophy (DMD), a fatal genetic X-linked pediatric disease, have been designed based on the limited understanding of natural disease progression and variability in clinical measures over different stages of the continuum of the disease. The objective was to inform the design of DMD clinical trials by developing a disease progression modelbased clinical trial simulation (CTS) platform based on measures commonly used in DMD trials. Data were integrated from past studies through the Duchenne Regulatory Science Consortium founded by the Critical Path Institute (15 clinical trials and studies, 1505 subjects, 27,252 observations). Using a nonlinear mixedeffects modeling approach, longitudinal dynamics of five measures were modeled (NorthStar Ambulatory Assessment, forced vital capacity, and the velocities of the following three timed functional tests: time to stand from supine, time to climb 4 stairs, and 10 meter walk-run time). The models were validated on external data sets and captured longitudinal changes in the five measures well, including both early disease when function improves as a result of growth and development and the decline in function in later stages. The models can be used in the CTS platform to perform trial simulations to optimize the selection of inclusion/ exclusion criteria, selection of measures, and other trial parameters. The data sets and models have been reviewed by the US Food and Drug Administration and the European Medicines Agency; have been accepted into the Fit-for-Purpose and Qualification for Novel Methodologies pathways, respectively; and will be submitted for potential endorsement by both agencies.
We analysed LCP efficiency in type B and type C wrist fractures (according to the AO Classification). We treated 58 wrist fractures (19 B-type fractures and 39 C-type fractures) in 35 male and 23 female patients, aged 19 to 87 years. Forty-one cases were followed up for an average period of 13 months. We performed a volar approach on 32 patients, a dorsal approach on five, and a double approach on four (both volar and dorsal). Twenty-six cases were pre-operatively examined with CT. All patients were evaluated using the "Mayo modified wrist score", with an excellent/good result in 76% of patients and a satisfactory/poor result in 24%. The LCP system proved to be adequately reliable and stable to keep the reduction in complex fractures (e.g. the C-type fractures in patients with low bone quality).
The treatment of chronic scapholunate ligament tears in patients with high demand, such as young athletes, is difficult as traditional techniques are associated with some loss of wrist motion and grip strength. This retrospective investigation studied young athletes (≤20 years old) with chronic scapholunate ligament lesions and a minimum follow-up of 24 months, treated with a modified Viegas dorsal capsuloplasty. Twenty-six young athletes (mean age 17 years) were included. A partial scapholunate ligament tear (Geissler III) was seen in 25 patients. At the last follow-up, a significantly different improvement was seen in all measured parameters and all patients could return to their original competitive activity, within 6 months (range 4–12) after surgery. Level of evidence: IV
Twenty patients with palpable swellings of the hand were investigated by computed tomography. The results, when compared with the pathological findings, lead us to consider this a technique of considerable value in the assessment of this kind of disease. The importance of angiography and, occasionally of magnetic resonance imaging, are also stressed.
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