Safety, tolerability and efficacy of intra-articular Progenza in knee osteoarthritis: a randomized double-blind placebo-controlled single ascending dose study.

BACKGROUND: Cell therapies are being investigated as potential disease modifying treatment options for osteoarthritis (OA). Progenza (PRG) comprises in vitro expanded mesenchymal stem cells derived from human donor adipose tissue combined with cell culture supernatant. The primary objective of this first-in-human study was to evaluate the safety and tolerability of PRG. METHODS: We conducted a single centre, randomized, double-blind, placebo-controlled, single ascending dose study. Twenty patients aged 40-65 years with symptomatic Kellgren-Lawrence grade 1-3 knee OA were treated in two cohorts and randomized 4:1 to PRG or placebo. Cohort 1: 3.9 million cells (PRG 3.9M, n = 8) or placebo (n = 2) and cohort 2: 6.7 million cells (PRG 6.7M, n = 8) or placebo (n = 2). Each patient received a single intra-articular injection and was followed-up for 12 months. RESULTS: The study population comprised 20 patients (placebo, n = 4; PRG 3.9M, n = 8; PRG 6.7M, n = 8). All patients reported at least one treatment-emergent adverse event (TEAE). The majority of events [143/169 (84.6%)] were mild with 34 (20.1%) being considered by the investigator to be treatment related. There were no serious AEs or withdrawals due to AEs during the study. There was a statistically significant within group improvement in VAS pain scores from baseline at all timepoints for the PRG combined group, with highly significant improvements seen at months 3, 6, 9 and 12 (p ≤ 0.005) while VAS pain scores in the placebo group showed marginal improvement. A statistically significant improvement was also seen in WOMAC pain subscale scores from baseline at all timepoints for the PRG combined group while a marginal improvement in the placebo group was not statistically significant. Between screening and month 12, there was no decrease in average lateral tibial cartilage volume in the PRG 3.9M group while the placebo group showed a statistically significant cartilage loss. This difference between the placebo and PRG 3.9M group was statistically significant (LSM difference 106.47 mm3, 95% CI 13.56 mm3, 199.37 mm3, p = 0.028). CONCLUSION: When administered as a single intra-articular injection to patients with symptomatic knee OA, PRG was safe and well tolerated. Furthermore, measurable improvements in symptoms and knee structure outcomes warrant further studies on PRG's potential for disease modification in OA. Trial registration ANZCTR, ACTRN12615000439549. Date registered: 7th May 2015, https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=368355.

An alternative slump reduction technique of anterior shoulder dislocations: a 3-year prospective study.

OBJECTIVE: To describe an alternative method of dislocated shoulder reduction and to investigate its success rate when used at a ski resort setting. DESIGN: A prospective observational study. SETTING: Medical center at Australia's largest ski resort during the ski seasons of 1994, 1995, and 1996 (June through early October). The center is a primary care private practice. PATIENTS: There were 199 patients with anterior dislocated shoulders who presented to the center. One patient was excluded from the study because of spontaneous reduction during clothing removal. INTERVENTIONS: Patients had upper body clothing removed, were seated in a chair, and supported in a slumped position by an assistant. The medical officer then performed the reduction once relaxation was achieved. Patients were always offered Entenox (nitrous oxide). MAIN OUTCOME MEASURES: Successful reduction of the anterior dislocated shoulder with or without analgesia. Any complications such as fractures and nerve damage were recorded. RESULTS: The data were recorded by the treating medical officer. 93.2% of the subjects were successfully treated using the "slump" reduction method. The success rate on first attempt using the slump method was 85.6%. Of the remainder, four subjects were reduced by an alternative method and five were sent to hospital for reduction under general anesthesia. Four of these subjects had fractures. CONCLUSION: The slump method of reduction for anterior dislocated shoulders compares favorably with previously documented methods. It would seem to be a particularly useful method when parenteral analgesia is either not available or relatively contraindicated. There were no complications resulting from the use of this method, and it is a method that is easy to learn. The slump method is a safe and effective addition to the primary care physician's options in reducing an anteriorly dislocated shoulder.