Meta-analysis of pain and function placebo responses in pharmacological osteoarthritis trials.

OBJECTIVE: To evaluate contextual effects in the form of placebo responses (PRs) for patient-reported pain and function and objectively measured function in osteoarthritis (OA) clinical trials. METHODS: Two authors independently searched major electronic databases from inception to 20 May 2019. Included studies were randomized, placebo-controlled OA trials of pharmacological agents reporting both patient-reported and objectively measured outcomes. PRs for each type of outcome measure were compared by standardized mean differences (SMDs). The placebo response ratio (PRR) assessed the placebo to treatment effect size. The effect sizes of PRs and PRRs were pooled using a random effects model. RESULTS: Twenty-one trials met the inclusion criteria; 20 were double-blinded with one not reporting on blinding status. Compared with patients' self-reported outcome (PRO) pain, PRs were significantly lower for PRO function (SMD - 0.16 [95% CI = - 0.28, - 0.05], p = 0.006), objectively measured muscle strength (SMD - 0.34 [95% CI - 0.58, - 0.10], p = 0.006), and range of motion (SMD = - 0.31 [95% CI = - 0.54, - 0.08], p = 0.008) function. Generally, PRs for function outcomes (patient-reported and objectively measured) were similar. The overall PRR for different measures ranged from the smallest (most favorable) for walking time/distance (0.30, 95% CI 0.16 to 0.43) to the largest for PRO pain (0.44, 95% CI 0.23 to 0.65). CONCLUSION: Function measures both subjective and objective had less contextual effects than pain measures in OA trials. Our results support the OMERACT-OARSI recommendations to include measures of physical function in all clinical trials of hip and knee OA and suggest that a greater use of function measures might enhance the success rates of pharmacological OA trials. Increasing the availability of mobile health apps should facilitate the acquisition of measured function data.

Tranexamic Acid Plus Low-dose Epinephrine Reduces Blood Loss in Total Knee Arthroplasty: A Systematic Review and Meta-analysis.

The present study assessed the effectiveness of the combined administration of tranexamic acid (TXA) plus low-dose epinephrine in primary total knee arthroplasty (TKA). We searched the following Chinese electronic databases: China National Knowledge Infrastructure and WanFang Data. We also searched the following English electronic databases: PubMed, Embase, Web of Science, and Central Register of Controlled Trials. To search for additional eligible studies, we also used Google's search engine. All randomized controlled trials (RCT) comparing TXA plus low-dose epinephrine (Combined group) and TXA alone in TKA were systematically searched. The primary outcomes were total blood loss, hidden blood loss, the requirement for transfusion, maximum hemoglobin (Hb) drop, and deep venous thrombosis (DVT). Drainage volume, operation time, length of stay, hospital for special surgery (HSS) score, and range of motion (ROM) were considered as secondary outcomes. Subgroup analyses were performed to assess the benefits of using a tourniquet and the application routes of topical or intravenous TXA between the two groups. Statistical analysis was assessed using RevMan 5.3 software. Four independent RCT were included involving 426 patients, with 213 patients in the Combined group and 213 patients in the TXA alone group. In the Combined group there was significant reduction in total blood loss (MD, 204.70; 95% CI, -302.76 to -106.63; P < 0.0001), hidden blood loss (MD, 185.63; 95% CI, -227.56 to -143.71; P < 0.00001), drainage volume (MD, 93.49; 95% CI, -117.24 to -69.74; P < 0.00001), and maximum Hb drop (MD, 5.33, 95% CI, -6.75 to -3.91; P < 0.00001). No statistical differences were found postoperatively in terms of the requirement for transfusion (risk ratio, 0.52; 95% CI, 0.26-1.04; P = 0.06), operation time (MD, 0.85; 95% CI, -2.62 to 4.31; P = 0.63), length of stay (MD, -0.02; 95% CI, -0.52 to 0.47; P = 0.93), HSS score (MD, 0.78; 95% CI, -0.36 to 1.92; P = 0.18), and ROM (MD, 1.40; 95% CI, -1.01 to 3.81; P = 0.26), and not increasing the risk of DVT (risk ratio, 1.00; 95% CI, 0.33 to 3.02; P = 1.00) in the two groups. This meta-analysis demonstrated that the administration of tranexamic acid plus low-dose epinephrine is a safe and efficacious treatment to reduce total blood loss, hidden blood loss, drainage volume, and maximum Hb drop in primary TKA, without increasing the risk of DVT in primary THA.

Dome osteotomy of the pelvis using a modified trochanteric osteotomy for acetabular dysplasia.

PURPOSE: Kawamura described his dome osteotomy of the pelvis using a standard trochanteric osteotomy. Here we present results of our modification of Kawamura's dome osteotomy using a modified trochanteric osteotomy. METHODS: We retrospectively analysed 34 out of 36 patients operated upon between 1993 and 2008. We reviewed the mid-term functional and radiological results with a mean follow-up of 67 months. There were 23 females and 11 males with a mean age of 30 years. RESULTS: The mean Harris hip score improved from 60 to 85 (p < 0.05) at the final follow-up. The functional results were excellent in 12, good in 14, fair in five and poor in three patients. Pain relief was a constant feature in all patients. Seventeen patients reported improvement in their ability to squat and sit cross-legged, 14 patients reported no change while three reported a worsening. Preoperatively 28 patients had an antalgic gait which improved in 14 patients following the surgery. Centre edge angle, acetabular angle, acetabular head index and weight bearing joint space improved significantly. This improved joint space was maintained at the last follow-up. Three cases had converted to total hip arthroplasty at the last follow-up. CONCLUSION: The mid-term functional and radiological results of the dome osteotomy using modified trochanteric osteotomy were found to be satisfactory. We conclude that it is a reasonable treatment option for young patients with symptomatic acetabular dysplasia.

Mevinolin enhances osteogenic genes (ALP, type I collagen and osteocalcin), CD44, CD47 and CD51 expression during osteogenic differentiation.

AIMS: In this study, we evaluated the effect of mevinolin on the expressions of osteogenic genes and surface molecules expression during osteogenesis. MAIN METHODS: D1 cells were cultured in osteogenic differentiation medium (ODM) for 6 days, treated with mevinolin for 2 days, and then subjected to alizarin red S staining, MTT assays, alkaline phosphatase (ALP) activity determinations, energy dispersive X-ray spectrophotometry (EDX), real-time PCR, Western blot, fluorescence microscopy and FACS analysis. KEY FINDINGS: Mevinolin is commonly prescribed and widely used to lower cholesterol levels, and offers an important, effective approach to the treatment of hypercholesterolemia and arteriosclerosis. However, the direct effect of mevinolin on osteogenesis in vitro has not been clarified. ODM has been previously shown to increase the osteoblast differentiation of D1 cells. In the present study, we investigated the expressions of osteogenic genes and surface molecules during osteoblast differentiation induced by mevinolin. We found that the induction of ALP, type I collagen, osteocalcin, CD44, CD47 and CD51 by mevinolin is responsible for the osteoblastic differentiation of D1 cells. SIGNIFICANCE: Our data show that mevinolin enhances the expressions of proteins and surface molecules related to osteogenesis.