Early rehabilitation after total knee replacement surgery: a multicenter, noninferiority, randomized clinical trial comparing a home exercise program with usual outpatient care.

OBJECTIVE: To determine, at 6 weeks postsurgery, if a monitored home exercise program (HEP) is not inferior to usual care rehabilitation for patients undergoing primary unilateral total knee replacement (TKR) surgery for osteoarthritis. METHODS: We conducted a multicenter, randomized clinical trial. Patients ages 45-75 years were allocated at the time of hospital discharge to usual care rehabilitation (n = 196) or the HEP (n = 194). Outcomes assessed 6 weeks after surgery included the Western Ontario and McMaster Universities Osteoarthritis Index pain and physical function subscales, knee range of motion, and the 50-foot walk time. The upper bound of the 95% confidence interval (95% CI) mean difference favoring usual care was used to determine noninferiority. RESULTS: At 6 weeks after surgery there were no significant differences between usual care and HEP, respectively, for pain (7.4 and 7.2; 95% CI mean difference [MD] -0.7, 0.9), physical function (22.5 and 22.4; 95% CI MD -2.5, 2.6), knee flexion (96° and 97°; 95% CI MD -4°, 2°), knee extension (-7° and -6°; 95% CI MD -2°, 1°), or the 50-foot walk time (12.9 and 12.9 seconds; 95% CI MD -0.8, 0.7 seconds). At 6 weeks, 18 patients (9%) allocated to usual care and 11 (6%) to the HEP did not achieve 80° knee flexion. There was no difference between the treatment allocations in the number of hospital readmissions. CONCLUSION: The HEP was not inferior to usual care as an early rehabilitation protocol after primary TKR.

Arx is required for normal enteroendocrine cell development in mice and humans.

Enteroendocrine cells of the gastrointestinal (GI) tract play a central role in metabolism, digestion, satiety and lipid absorption, yet their development remains poorly understood. Here we show that Arx, a homeodomain-containing transcription factor, is required for the normal development of mouse and human enteroendocrine cells. Arx expression is detected in a subset of Neurogenin3 (Ngn3)-positive endocrine progenitors and is also found in a subset of hormone-producing cells. In mice, removal of Arx from the developing endoderm results in a decrease of enteroendocrine cell types including gastrin-, glucagon/GLP-1-, CCK-, secretin-producing cell populations and an increase of somatostatin-expressing cells. This phenotype is also observed in mice with endocrine-progenitor-specific Arx ablation suggesting that Arx is required in the progenitor for enteroendocrine cell development. In addition, depletion of human ARX in developing human intestinal tissue results in a profound deficit in expression of the enteroendocrine cell markers CCK, secretin and glucagon while expression of a pan-intestinal epithelial marker, CDX2, and other non-endocrine markers remained unchanged. Taken together, our findings uncover a novel and conserved role of Arx in mammalian endocrine cell development and provide a potential cause for the chronic diarrhea seen in both humans and mice carrying Arx mutations.