Study protocol: a double blind randomised control trial of high volume image guided injections in Achilles and patellar tendinopathy in a young active population

Abstract Background Chronic tendinopathy is a significant problem particularly in active populations limiting sporting and occupational performance. The prevalence of patellar tendinopathy in some sports is near 50% and the incidence of lower limb tendinopathy is 1.4% p.a. in the UK Military. Management includes isometric, eccentric, heavy slow resistance exercises and extracorporeal shockwave therapy (ESWT). Often these treatments are inadequate yet there is no good evidence for injection therapies and success rates from surgery can be as low as 50%. High Volume Image Guided Injection (HVIGI) proposes to strip away the neovascularity and disrupt the nerve ingrowth seen in chronic cases and has shown promising results in case series. This study aims to investigate the efficacy of HVIGI in a randomised controlled trial (RCT). Methods RCT comparing 40ml HVIGI, with or without corticosteroid, with a 3ml local anaesthetic sham-control injection. Ninety-six participants will be recruited. Inclusion criteria: male, 18–55 years old, chronic Achilles or patellar tendinopathy of at least 6 months, failed conservative management including ESWT, and Ultrasound (US) evidence of neovascularisation, tendon thickening and echogenic changes. Outcome measures will be recorded at baseline, 6 weeks, 3, 6 and 12 months. Primary outcome measures include The Victoria Institute of Sport Assessments for Achilles and patellar tendinopathy (VISA-A and VISA-P) and VAS pain. Secondary outcome measures include Modified Ohberg score, maximum tendon diameter and assessment of hypoechoic appearance on US, and Functional Activity Assessment. Discussion Despite previous interventional trials and reviews there is still insufficient evidence to guide injectable therapy for chronic tendinopathy that has failed conservative treatment. The scant evidence available suggests HVIGI has the greatest potential however there is no level one RCT evidence to support this. Investigating the efficacy of HVIGI against control in a RCT and separating the effect of HVIGI and corticosteroid will add high level evidence to the management of chronic tendinopathy resistant to conservative treatment. Trial Registration EudraCT: 2015-003587-36 3 Dec 201

Rationalizing underprediction of drug clearance from enzyme and transporter kinetic data: From in vitro tools to mechanistic modeling

Over the years, there has been an increase in the number and quality of available in vitro tools for the assessment of clearance. Complexity of data analysis and modelling of corresponding in vitro data has increased in an analogous manner, in particular for the simultaneous characterization of transporter and metabolism kinetics, together with intracellular binding and passive diffusion. In the current chapter, the impact of different factors on the in vitro-in vivo extrapolation of clearance will be addressed in a stepwise manner, from the selection of the most adequate in vitro system and experimental design/condition to the corresponding modelling of data generated. The application of static or physiologically based pharmacokinetic models in the prediction of clearance will be discussed, highlighting limitations and current challenges of some of the approaches. Particular focus will be on the ability of in vitro and in silico predictive tools to overcome the trend of clearance underprediction. Improvements made as a result of inclusion of extrahepatic metabolism and consideration of transporter-metabolism interplay across different organs will be discussed. © Springer Science+Business Media, LLC 2014