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Medial tibial stress fractures occur secondary to failure in shear. It has been proposed that the use of functional foot orthotics (FFOs) may decrease their incidence by positioning the subtalar joint in the neutral position at heel strike. The purpose of this study was to evaluate the scientific basis of this concept by in-vivo measurement of tibial principal strain, the principal strain angle and shear strains during treadmill walking from rosette strain gauges bonded to the tibia of a male subject at two sites prone to stress fracture. Recordings were made while wearing Rockport walking shoes without orthotics, with non-posted graphite orthotics, with neutral rearfoot posted polypropylene orthotics, with 4° varus rearfoot posted polypropylene orthotics, and with neutral rearfoot posted kinetic wedge polypropylene orthotics designed to treat hallux limitus. None of the various modifications of FFOs tested in this study had a statistically significant effect on the compression strains during treadmill walking compared to the walking shoe alone, indicating that they were not affective in attenuating the ground reaction force. Their use was associated with a 22–51% increase in principal (p <.001) and a 9–35% increase in tibial shear strains (p =.003). The compression and shear strains and the angle of the principal strains (p <.001) were higher at the distal than at the proximal recording site, (p <.001 for all). The findings do not support the use of FFOs in any of the posting configurations tested as a means for lowering tibial shear strains or the concept of the biomechanical importance of the neutral position of the subtalar joint at heel strike. [ABSTRACT FROM AUTHOR]

Summary: Background: Namodenoson, an A3 adenosine receptor (A3AR) agonist, improved liver function/pathology in non‐alcoholic steatohepatitis (NASH) preclinical models. Aim: To evaluate the efficacy and safety of namodenoson for the treatment of non‐alcoholic fatty liver disease (NAFLD) with or without NASH Methods: This phase 2 study included 60 patients with NAFLD (ALT ≥60 IU/L) who were randomised (1:1:1) to oral namodenoson 12.5 mg b.d. (n = 21), 25 mg b.d. (n = 19), or placebo (n = 20) for 12 weeks (total follow‐up: 16 weeks). The main efficacy endpoint involved serum ALT after 12 weeks of treatment. Results: Serum ALT decreased over time with namodenoson in a dose‐dependent manner. The difference between change from baseline (CFB) for ALT in the namodenoson 25 mg b.d. arm vs placebo trended towards significance at 12 weeks (P = 0.066). Serum AST levels also decreased with namodenoson in a dose‐dependent manner; at 12 weeks, the CFB for 25 mg b.d. vs placebo was significant (P = 0.03). At Week 12, 31.6% in the namodenoson 25 mg b.d. arm and 20.0% in the placebo arm achieved ALT normalisation (P = 0.405). At week 16, the respective rates were 36.8% and 10.0% (P = 0.038). A3AR expression levels were stable over time across study arms. Both doses of namodenoson were well tolerated with no drug‐emergent severe adverse events, drug‐drug interactions, hepatotoxicity, or deaths. Three adverse events were considered possibly related to study treatment: myalgia (12.5 mg b.d. arm), muscular weakness (25 mg b.d. arm), and headache (25 mg b.d. arm). Conclusion: A3AR is a valid target; namodenoson 25 mg b.d. was safe and demonstrated efficacy signals (ClinicalTrials.gov #NCT02927314). [ABSTRACT FROM AUTHOR]

LINKED CONTENT: This article is linked to Safadi et al papers. To view these articles, visit https://doi.org/10.1111/apt.16664 and https://doi.org/10.1111/apt.16748 [ABSTRACT FROM AUTHOR]