Three once-weekly intra-articular injections of Hylan G-F 20 significantly improve pain relief compared with placebo in patients with chronic idiopathic knee osteoarthritis: a single-centre, evaluator-blinded and patient-blinded, randomized controlled trial.

Background: Clinical trials on the use of viscosupplementation with hyaluronic acid (HA) in patients with knee osteoarthritis (KOA) are inconsistent, making it challenging to determine its value in clinical practice. One issue is the availability of various HA products on the market; differences in their chemical features can impact patient outcomes. Herein, we assess the efficacy and safety of three once-weekly intra-articular (IA) injections of Hylan G-F 20, a high-molecular-weight and highly crosslinked HA product, in patients with KOA. We hypothesized that Hylan G-F 20 would provide significant pain relief with no increased safety risk compared with IA saline (placebo). Methods: This was a 26-week, patient-blinded and evaluator-blinded, single-centre, randomized placebo- controlled trial. Men or women ≥18 years of age with Larsen grade II or III KOA were included. Patients received IA injections of either Hylan G-F 20 or placebo once a week for 3 weeks. The primary endpoints were the week 12 and 26 visits. Primary efficacy outcomes included visual analogue scale (VAS) pain scores, patient activity level and an overall assessment of clinical condition. Secondary outcomes included adverse events (AEs) that emerged during treatment. The primary analysis included the intention-to-treat population. An alpha level of 0.05 was used in the statistical analysis. Results: Thirty patients were included in the intention-to-treat population (15 per group). All efficacy outcomes were statistically significant in favour of Hylan G-F 20, except night pain and inactivity stiffness, for both patient- assessed (all p=0.0001 at week 12) and evaluator-assessed (all p=0.0001 at week 12 and p=0.0004-0.0180 at week 26) measurements. There was also a greater proportion of symptom-free patients and those with a >50% improvement in their VAS scores, except night pain, in the Hylan G-F 20 group (p=0.001-0.003 in patient-assessed scores and p<0.0001 to 0.002 in evaluator-assessed scores at week 12). Two patients, one in each group, experienced an AE; no sequelae occurred, and no special treatment was required for either AE. No patients withdrew from the study prematurely due to an AE. Conclusion: In patients with chronic idiopathic KOA, Hylan G-F 20 provides significant improvements in pain relief compared with placebo with no added safety concerns.

Effectiveness, Safety, and Costs of Thromboprophylaxis with Enoxaparin or Unfractionated Heparin Among Medical Inpatients With Chronic Obstructive Pulmonary Disease or Heart Failure.

Background: Chronic obstructive pulmonary disease (COPD) and heart failure (HF) are risk factors for venous thromboembolism (VTE). Enoxaparin and unfractionated heparin (UFH) help prevent hospital-associated VTE, but few studies have compared them in COPD or HF. Objectives: To compare effectiveness, safety, and costs of enoxaparin vs UFH thromboprophylaxis in medical inpatients with COPD or HF. Methods: This retrospective cohort study included adults with COPD or HF from the Premier PINC AI Healthcare Database. Included patients received prophylactic-dose enoxaparin or UFH during a >6-day index hospitalization (the first visit/admission that met selection criteria during the study period) between January 1, 2010, and September 30, 2016. Multivariable regression models assessed independent associations between exposures and outcomes. Hospital costs were adjusted to 2017 US dollars. Patients were followed 90 days postdischarge (readmission period). Results: In the COPD cohort, 114 174 (69%) patients received enoxaparin and 51 011 (31%) received UFH. Among patients with COPD, enoxaparin recipients had 21%, 37%, and 10% lower odds of VTE, major bleeding, and in-hospital mortality during index admission, and 17% and 50% lower odds of major bleeding and heparin-induced thrombocytopenia (HIT) during the readmission period, compared with UFH recipients (all P <.006). In the HF cohort, 58 488 (58%) patients received enoxaparin and 42 726 (42%) received UFH. Enoxaparin recipients had 24% and 10% lower odds of major bleeding and in-hospital mortality during index admission, and 13%, 11%, and 51% lower odds of VTE, major bleeding, and HIT during readmission (all P <.04) compared with UFH recipients. Enoxaparin recipients also had significantly lower total hospital costs during index admission (mean reduction per patient: COPD, 1280;HF,2677) and readmission (COPD, 379;HF,1024). Among inpatients with COPD or HF, thromboprophylaxis with enoxaparin vs UFH was associated with significantly lower odds of bleeding, mortality, and HIT, and with lower hospital costs. Conclusions: This study suggests that thromboprophylaxis with enoxaparin is associated with better outcomes and lower costs among medical inpatients with COPD or HF based on real-world evidence. Our findings underscore the importance of assessing clinical outcomes and side effects when evaluating cost-effectiveness.

Effectiveness, safety, and costs of thromboprophylaxis with enoxaparin or unfractionated heparin in inpatients with obesity.

Background: Obesity is a frequent and significant risk factor for venous thromboembolism (VTE) among hospitalized adults. Pharmacologic thromboprophylaxis can help prevent VTE, but real-world effectiveness, safety, and costs among inpatients with obesity are unknown. Objective: This study aims to compare clinical and economic outcomes among adult medical inpatients with obesity who received thromboprophylaxis with enoxaparin or unfractionated heparin (UFH). Methods: A retrospective cohort study was performed using the PINC AI™ Healthcare Database, which covers more than 850 hospitals in the United States. Patients included were ≥18 years old, had a primary or secondary discharge diagnosis of obesity [International Classification of Diseases (ICD)-9 diagnosis codes 278.01, 278.02, and 278.03; ICD-10 diagnosis codes E66.0x, E66.1, E66.2, E66.8, and E66.9], received ≥1 thromboprophylactic dose of enoxaparin (≤40 mg/day) or UFH (≤15,000 IU/day) during the index hospitalization, stayed ≥6 days in the hospital, and were discharged between 01 January 2010, and 30 September 2016. We excluded surgical patients, patients with pre-existing VTE, and those who received higher (treatment-level) doses or multiple types of anticoagulants. Multivariable regression models were constructed to compare enoxaparin with UFH based on the incidence of VTE, pulmonary embolism (PE)---------related mortality, overall in-hospital mortality, major bleeding, treatment costs, and total hospitalization costs during the index hospitalization and the 90 days after index discharge (readmission period). Results: Among 67,193 inpatients who met the selection criteria, 44,367 (66%) and 22,826 (34%) received enoxaparin and UFH, respectively, during their index hospitalization. Demographic, visit-related, clinical, and hospital characteristics differed significantly between groups. Enoxaparin during index hospitalization was associated with 29%, 73%, 30%, and 39% decreases in the adjusted odds of VTE, PE-related mortality, in-hospital mortality, and major bleeding, respectively, compared with UFH (all p < 0.002). Compared with UFH, enoxaparin was associated with significantly lower total hospitalization costs during the index hospitalization and readmission periods. Conclusions: Among adult inpatients with obesity, primary thromboprophylaxis with enoxaparin compared with UFH was associated with significantly lower risks of in-hospital VTE, major bleeding, PE-related mortality, overall in-hospital mortality, and hospitalization costs.

Three Weekly Intra-Articular Injections of Hylan G-F 20 vs Arthrocentesis in Patients with Chronic Idiopathic Knee Osteoarthritis: A Multicenter, Evaluator- and Patient-Blinded, Randomized Controlled Trial.

Background: Knee osteoarthritis is a leading cause of disability worldwide. Symptoms can vary over time, leading to episodes of worsened symptoms known as flares. Intra-articular injection of hyaluronic acid has demonstrated long-term symptomatic relief in the broader knee osteoarthritis population, although its use in the flare population has not been extensively examined. Objective: To assess the efficacy and safety of 3 once-weekly intra-articular injections of hylan G-F 20 (as single and repeat courses) in patients with chronic knee osteoarthritis, including a subpopulation that experienced flare. Methods: Prospective randomized controlled, evaluator- and patient-blinded, multicenter trial with 2 phases: hylan G-F 20 vs arthrocentesis only (control) and 2 courses vs single-course hylan G-F 20. Primary outcomes were visual analog scale (0-100 mm) pain scores. Secondary outcomes included safety and synovial fluid analysis. Results: Ninety-four patients (104 knees) were enrolled in Phase I, with 31 knees representing flare patients. Seventy-six patients (82 knees) were enrolled in Phase II. Long-term follow-up was 26 to 34 weeks. In flare patients, hylan G-F 20 showed significantly more improvement than the controls for all primary outcomes except pain at night (P = 0.063). Both 1 and 2 courses of hylan G-F 20 showed significant improvements from baseline for primary outcomes with no differences in efficacy between groups in the intention-to-treat population at the end of Phase II. Two courses of hylan G-F 20 showed better improvement in pain with motion (P = 0.0471) at long-term follow-up. No general side effects were reported, and local reactions (pain/swelling of the injected joint) resolved within 1 to 2 weeks. Hylan G-F 20 was also associated with reduced effusion volume and protein concentration. Conclusions: Hylan G-F 20 significantly improves pain scores vs arthrocentesis in flare patients with no safety concerns. A repeat course of hylan G-F 20 was found to be well tolerated and efficacious.