Regulatory Issues of Platform Trials: Learnings from EU-PEARL.

Although platform trials have many benefits, the complexity of these designs may result not only in increased methodological but also regulatory and ethical challenges. These aspects were addressed as part of the IMI project EU Patient-Centric Clinical Trial Platforms (EU-PEARL). We reviewed the available guidelines on platform trials in the European Union and the United States. This is supported and complemented by feedback received from regulatory interactions with the European Medicines Agency and the US Food and Drug Administration. Throughout the project we collected the needs of all relevant stakeholders including ethics committees, regulators, and health technology assessment bodies through active dialog and dedicated stakeholder workshops. Furthermore, we focused on methodological aspects and where applicable identified the corresponding guidance. Learnings from the guideline review, regulatory interactions, and workshops are provided. Based on these, a master protocol template was developed. Issues that still need harmonization or clarification in guidelines or where further methodological research is needed are also presented. These include questions around clinical trial submissions in Europe, the need for multiplicity control across the whole master protocol, the use of non-concurrent controls, and the impact of different randomization schemes. Master protocols are an efficient and patient-centered clinical trial design that can expedite drug development. However, they can also introduce additional operational and regulatory complexities. It is important to understand the different requirements of stakeholders upfront and address them in the trial. While relevant guidance is increasing, early dialog with relevant stakeholders can help to further support such designs.

Bilateral ruptures of the extensor mechanism of the knee: A systematic review.

INTRODUCTION: We conduct a systematic and qualitative review of the current literature to evaluate studies that described bilateral ruptures of the extensor mechanism of the knee. METHODS: A comprehensive literature search was performed to evaluate all studies included in the literature until September 2016. RESULTS: Fourteen studies with a total of 44 patients met the inclusion criteria. There were 14 patients with CRF (61%), 6 patients were affected by diabetes mellitus (14%) while other 6 patients were obese patients (14%). CONCLUSION: CRF represents the most frequent comorbidity in patients with bilateral quadriceps/patellar tendon ruptures.

Non-metallic implant for patellar fracture fixation: A systematic review.

INTRODUCTION: Despite good clinical outcome proposals, there has been relatively little published regarding the use of non-metallic implant for patellar fracture fixation. The purpose of the study was to perform a systematic literature review to summarize and evaluate the clinical studies that described techniques for treating patella fractures using non-metallic implants. METHODS: A comprehensive literature search was systematically performed to evaluate all studies included in the literature until November 2015. The following search terms were used: patellar fracture, patella suture, patella absorbable, patella screw, patella cerclage. Two investigators independently reviewed all abstracts and the selection of these abstracts was then performed based on inclusion and/or exclusion criteria. RESULTS: A total of 9 studies involving 123 patients were included. Patients had a mean age of 33.7 years and were followed up for a mean of 18.9 months. The most common method for fracture fixations included the use of suture material. Good clinical outcomes were reported among all studies. Thirteen patients (10.5%) presented complications, while 4 patients (3.2%) required additional surgery for implant removal. CONCLUSION: There is a paucity of literature focused on the use of non-metallic implant for patellar fracture fixation. However, this systematic review showed that non-metallic implants are able to deliver good clinical outcomes reducing the rate of surgical complications and re-operation. These results may assist surgeons in choosing to use alternative material such as sutures to incorporate into their routine practice or to consider it, in order to reduce the rate of re-operation.

Femoral neck's fracture in Fahr's Syndrome: case report.

Fahr's syndrome, also known as "Bilateral Striopallidodentate Calcinosis" (BSPDC) primitive, is a rare neurological disease characterized by the presence of idiopathic, bilateral, symmetrical and abnormal deposition of calcium in areas of the brain that control movements including the basal ganglia, dentate nuclei of the cerebellum, nuclei of thalamus and semi-oval center. We describe a case of a 76-year-old male patient underwent reduction and fixation of a subtrochanteric fracture with intramedullary nail. During post-operative rehabilitation therapists's patient management was difficult due to obvious extrapyramidal symptoms characterized by dysarthria, rigidity, bradykinesia, postural instability. A CT scan, performed for the onset of stiffness and confusion before the operation, showed: IV ventricle eumorphic and in axis; expansion in atrophic sense of supratentorial ventricular system; bilateral, diffuse and coarse calcifications of the basal ganglia in the cerebellar and occipital cortex, elements compatible with Fahr's syndrome. The patient presented repeated postural instability episodes in the upright position, with loss balance tendency and recurrent falls. Fahr's syndrome patient is a "weak" patient, which requires a multi-disciplinary approach in order to prevent the mobility reduction, to improve the condition of postural instability, thus reducing the risk of fractures using preventive measures in domestic environment.