Validation of the Hip Disability and Osteoarthritis Outcome Score and Knee Injury and Osteoarthritis Outcome Score Pain and Function Subscales for Use in Total Hip Replacement and Total Knee Replacement Clinical Trials.

BACKGROUND: Total hip replacement (THR)/total knee replacement (TKR) studies do not uniformly measure patient centered domains, pain, and function. We aim to validate existing measures of pain and function within subscales of standard instruments to facilitate measurement. METHODS: We evaluated baseline and 2-year pain and function for THR and TKR using Hip disability and Osteoarthritis Outcome Score (HOOS)/Knee Injury and Osteoarthritis Outcome Score (KOOS), with primary unilateral TKR (4796) and THR (4801). Construct validity was assessed by correlating HOOS/KOOS pain and activities of daily living (ADL), function quality of life (QOL), and satisfaction using Spearman correlation coefficients. Patient relevant thresholds for change in pain and function were anchored to improvement in QOL; minimally clinically important difference (MCID) corresponded to "a little improvement" and a really important difference (RID) to a "moderate improvement." Pain and ADL function scores were compared by quartiles using Kruskal-Wallis. RESULTS: Two-year HOOS/KOOS pain and ADL function correlated with health-related QOL (KOOS pain and Short Form 12 Physical Component Scale ρ = 0.54; function ρ = 0.63). Comparing QOL by pain and function quartiles, the highest levels of pain relief and function were associated with the most improved QOL. MCID for pain was estimated at ≥20, and the RID ≥29; MCID for function ≥14, and the RID ≥23. The measures were responsive to change with large effect sizes (≥1.8). CONCLUSION: We confirm that HOOS/KOOS pain and ADL function subscales are valid measures of critical patient centered domains after THR/TKR, and achievable thresholds anchored to improved QOL. Cost-free availability and brevity makes them feasible, to be used in a core measurement set in total joint replacement trials.

Postoperative Myocardial Injury and Inflammation Is Not Blunted by a Trial of Atorvastatin in Orthopedic Surgery Patients.

BACKGROUND: Orthopedic patients are at risk for adverse postoperative cardiovascular outcomes. QUESTIONS/PURPOSES: This pilot randomized controlled trial (RCT) of atorvastatin vs. placebo in orthopedic surgery patients was performed in order to assess: (1) the prevalence of perioperative myocardial injury; (2) the effect of atorvastatin on perioperative inflammation; and (3) the feasibility of performing a large RCT of statin therapy in orthopedic patients. METHODS: Hip fracture (hip Fx) and total hip and knee replacement (THR and TKR) patients were randomized 1:1 to atorvastatin 40 mg daily vs. placebo, starting preoperatively and continuing until postoperative day (POD) 45. High-sensitivity cardiac troponin I (hs-cTnI), high-sensitivity C-reactive protein (hs-CRP), and interleukin-6 (IL-6) were measured preoperatively and on POD 2. Patients were monitored for adverse events until POD 90. RESULTS: Five hundred fifty-six patients were screened, 22 were recruited (4 hip Fx, 11 THR, 7 TKR), and 2 withdrew. Most (80%) had detectable hs-cTnI (> 1.1 pg/mL) preoperatively. Twenty percent had a perioperative rise in hs-cTnI (≥ 10 pg/mL), which was not blunted by atorvastatin. Hs-CRP rose in 19/20 patients, and IL-6 rose in all patients. However, atorvastatin did not blunt the rise in these inflammatory biomarkers. On POD 2, IL-6 and hs-cTnI levels correlated (ρ = 0.59, p = 0.02). Recruitment was limited by the high prevalence of statin use in the screened population and a high prevalence of exclusions among hip fracture patients. CONCLUSION: Perioperative myocardial injury and inflammation are common in orthopedic patients and do not appear to be reduced in those randomized to atorvastatin. TRIAL REGISTRATION: NCT02197065.

Preliminary results of a phase II trial of proton radiotherapy for pediatric rhabdomyosarcoma.

PURPOSE: This prospective phase II study was designed to assess disease control and to describe acute and late adverse effects of treatment with proton radiotherapy in children with rhabdomyosarcoma (RMS). PATIENTS AND METHODS: Fifty-seven patients with localized RMS (age 21 years or younger) or metastatic embryonal RMS (age 2 to 10 years) were enrolled between February 2005 and August 2012. All patients were treated with chemotherapy based on either vincristine, actinomycin, and cyclophosphamide or vincristine, actinomycin, and ifosfamide-based chemotherapy and proton radiation. Surgical resection was based on tumor site and accessibility. Common Terminology Criteria for Adverse Events, Version 3.0, was used to assess and grade adverse effects of treatment. Concurrent enrollment onto Children's Oncology Group or European Pediatric Sarcoma Study Group protocols was allowed. All pathology and imaging were reviewed at the treating institution. RESULTS: Median follow-up was 47 months (range, 14 to 102 months) for survivors. Five-year event-free survival (EFS), overall survival (OS), and local control (LC) were 69%, 78%, and 81%, respectively, for the entire cohort. The 5-year LC by risk group was 93% for low-risk and 77% for intermediate-risk disease. There were 13 patients with grade 3 acute toxicity and three patients with grade 3 late toxicity. There were no acute or late toxicities higher than grade 3. CONCLUSION: Five-year LC, EFS, and OS rates were similar to those observed in comparable trials that used photon radiation. Acute and late toxicity rates were favorable. Proton radiation appears to represent a safe and effective radiation modality for pediatric RMS.