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.

Evaluation of Hylan G-F 20 Treatment with Opioid Prescriptions and Intraarticular Corticosteroid Injections in Patients with Osteoarthritis of the Knee Using a Claims Database.

OBJECTIVE: Assess how treatment with the viscosupplement hylan G-F 20 relates to opioid prescriptions and intraarticular corticosteroid injections (IACS) in patients with osteoarthritis of the knee (OAK). DESIGN: Case-crossover; adult patients with OAK identified in a claims database were treated with hylan G-F 20 from July 1, 2007, to June 29, 2017. Opioid or IACS prescriptions in the 6 months before treatment were compared to the 6 months after. Patients with comorbid conditions requiring pain medications were excluded, resulting in a 29,395-patient cohort. Four subgroups were investigated: patients with (1) opioids before hylan G-F 20 (OB; n = 6,609); (2) opioids before and after hylan G-F 20 (OBF; n = 3,320); (3) IACS before hylan G-F 20 (CB; n = 11,162); and (4) IACS before and after hylan G-F 20 (CBF; n = 2,810). All opioids were converted to morphine milligram equivalents (MME). RESULTS: OB subgroup patients had a significant decrease (P < 0.01) in total MME (-14.0%), MME per day (-14.2%) and opioid prescription days (-12.6%) after treatment versus before. Only 50.2% of patients prescribed opioids before hylan G-F 20 were prescribed an opioid after treatment. OBF subgroup patients had a significant increase (P < 0.01) in opioid prescription days (7.8%) before versus after treatment. There was a significant decrease (P < 0.01) in the number of IACS after versus before treatment for the Total Cohort (-56.1%), and subgroups CB (-72.6%) and CBF (-4.1%). A total of 74.8% of patients receiving an IACS before treatment did not receive an IACS after treatment. CONCLUSIONS: Hylan G-F 20 is associated with a reduction in opioid prescriptions and IACS in OAK patients.

Efficacy of Triamcinolone Acetonide Extended-Release in Participants with Unilateral Knee Osteoarthritis: A Post Hoc Analysis.

INTRODUCTION: Osteoarthritis (OA) is common and its prevalence is increased in military service members. In a phase 3 randomized controlled trial (NCT02357459), a single intra-articular injection of an extended-release formulation of triamcinolone acetonide (TA-ER) in participants with unilateral or bilateral knee OA demonstrated substantial improvement in pain and symptoms. Bilateral knee pain has emerged as a confounding factor in clinical trials when evaluating the effect of a single intra-articular injection. Furthermore, unilateral disease is frequently first to emerge in active military personnel secondary to prior traumatic joint injury. In this post hoc analysis, we assessed efficacy and safety of TA-ER in a subgroup of participants with unilateral knee OA. METHODS: Participants ≥ 40 years of age with symptomatic knee OA were randomized to a single intra-articular injection of TA-ER 32 mg, TA crystalline suspension (TAcs) 40 mg, or saline-placebo. Average daily pain (ADP)-intensity and rescue medication use were collected at each of weeks 1-24 postinjection; Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC)-A (pain), WOMAC-B (stiffness), WOMAC-C (function), and Knee Injury and Osteoarthritis Outcome Score Quality of Life (KOOS-QoL) were collected at weeks 4, 8, 12, 16, 20, and 24 postinjection. Adverse events (AEs) were assessed throughout the study. Participants with unilateral knee OA were selected for this analysis. RESULTS: Of 170 participants with unilateral OA (TA-ER, N = 51; saline-placebo, N = 60; TAcs, N = 59), 42% were male and 89% were white. TA-ER significantly (p < 0.05) improved ADP-intensity vs. saline-placebo (weeks 1-24) and TAcs (weeks 4-21). TA-ER significantly (p < 0.05) improved WOMAC-A vs. saline-placebo (all time points) and TAcs (weeks 4, 8, 12, 24). Consistent outcomes were observed for rescue medication, WOMAC-B, WOMAC-C, and KOOS-QoL. AEs were similar in frequency/type across treatments. CONCLUSION: TA-ER provided 5-6 months' pain relief that consistently exceeded saline-placebo and TAcs, suggesting that TA-ER injected intra-articularly into the affected knee may be an effective non-opioid treatment option. Although the participants included in this analysis did not fully represent the diverse demographics of active service members, the substantial unmet medical need in the military population suggests that TA-ER may be an important treatment option; additional studies of TA-ER in active military patients are needed. TRIAL REGISTRATION: ClinicalTrials.gov NCT02357459. FUNDING: Flexion Therapeutics, Inc. Plain language summary available for this article.

Multimodal Pain Strategies Including Liposomal Bupivacaine for Isolated Acetabular Fracture Surgery.

BACKGROUND: The incidence of isolated acetabular fractures has been increasing, particularly in older adult patients. These fractures can be debilitating and may require prolonged immobilization and/or complex surgical reconstruction. Liposomal bupivacaine (LB) is a prolonged-release form of bupivacaine demonstrated to be effective in orthopaedic surgery. Defining a multimodal pain management plan, which incorporates optimized techniques for use of LB in acetabular surgery, may improve outcomes for patients. METHODS: Two orthopaedic surgeons specializing in orthopaedic traumatology discussed best practices for infiltration of LB and recommendations for perioperative use of LB plus other anesthetics/analgesics for isolated acetabular fracture surgery. RESULTS: Consensus techniques for isolated posterior and anterior acetabular fractures were developed. LB (266 mg/20 mL) should be expanded with 50 mL of bupivacaine HCl 0.25% and saline to a total volume of 120 or 300 mL for the posterior or anterior techniques, respectively. A 3.5-inch spinal needle is inserted tangentially, infiltrating 1 mL/cm into the fracture site, periosteum, muscle fascia, subcutaneous tissue, and skin. Patients receive acetaminophen, celecoxib, gabapentin, and opioids before surgery, adjusting appropriately for patient comorbidities and potential drug-drug interactions. At the end of the surgery, before closure, LB is infiltrated and patients receive a dose of intravenous acetaminophen. Presurgical medications are continued after surgery for approximately 10-14 days, after which opioids are only considered to treat breakthrough pain. CONCLUSIONS: These recommendations can be used to optimize and streamline care for patients with isolated acetabular fractures and act as a foundation for additional clinical research. LEVEL OF EVIDENCE: Therapeutic Level V.

Viscosupplementation for treating osteoarthritis in the military population.

Military personnel have a greater risk of developing osteoarthritis (OA) than the general population. OA is a chronic, painful, and debilitating disease with a high cost burden. Compared with the general population, a higher prevalence of post-traumatic OA has been reported in the military. Using recent literature, we aim to improve the understanding of post-traumatic OA, with an exploration of the pathophysiology of OA. Our review encompasses the current treatment modalities for alleviating the pain from OA with a focus on viscosupplementation. A multimodal approach may be beneficial for the relief of OA pain and improvement of function in military personnel with early OA, and may lower the cost burden.

Conservative treatment modalities and outcomes for osteoarthritis: the concomitant pyramid of treatment.

This article reviews current treatment algorithms for the conservative treatment of hip and knee osteoarthritis. The available treatment options for osteoarthritis (physical therapy, medical therapeutics, steroid injections, nutraceuticals, hyaluronic acid injections, acupuncture, pulsed electrical stimulation, and topical ointments) are compared to determine efficacy in the treatment of pain and return of function in the osteoarthritic joint. A literature review was conducted to determine combinations of appropriate concomitant therapy. Based on the available literature, we conclude that an early transition to multimodal and concomitant therapy is the most efficacious approach to decrease pain and improve joint function in the osteoarthritic hip and knee.

Terrorism and blast phenomena: lessons learned from the attack on the USS Cole (DDG67).

Blast phenomena and injuries to the musculoskeletal system have been well documented for the past 50 years. The USS Cole was attacked in Aden Harbor in Yemen on October 12, 2000. Seventeen sailors were killed and 39 were wounded. The bombing of the USS Cole and an analysis of the pattern of injury are unique compared with previous terrorist bombing attacks in which the predominant injury pattern is from Type II and Type III blast phenomena. Because the ship superstructure did not collapse, there were no confounding variables in examining the pattern of injury as there would have been with shrapnel-generating devices or detonations with subsequent building collapse. The morbidity and mortality sustained by the victims was almost exclusively from Type I and Type III blast effects. The musculoskeletal system was a clear marker for mortality and morbidity. Fractures of the cranium, spine, pelvis, and long bones denoted increasing severity of injury to critical organ systems. Shipboard firefighting was successful in containing fires and there was very little morbidity from inhalational injuries or burns. Blast phenomena that affect ships or buildings that have been specifically built to absorb a blast attack likely will manifest a different mode and pattern of injury than those seen in traditional terrorist blast events.

Treatment of the mangled lower extremity after a terrorist blast injury.

Terrorist bombings, with resultant blast injuries, have been increasing in frequency during the past 30 years. Injury to the musculoskeletal system is common in victims who survive such attacks. Substantial injury to the limbs may occur through several different mechanisms, each of which may affect prognosis and alter the treatment algorithm. An analysis of the available literature on terrorism and blast events revealed that resource use of the treating medical facility is high during the initial hours after a blast attack, but usually is manageable. A resource management protocol was developed to organize the treatment of limb salvage into four phases. This management protocol may improve the medical facility's ability to manage system resources while treating patients with severe blast injuries. The decision of whether to salvage or proceed with limb amputation is one of the most difficult in orthopaedic trauma. A basic education in the mechanisms of blast damage, a methodical approach to resuscitation, and mangled extremity treatment, likely can improve surgical success.

An analysis of orthopaedic liability in the acute care setting.

The risk of litigation in the emergency room is not directly proportional to the severity of injury. In fact, the risk of initiation of legal action is greater in cases of relatively modest permanent and partial disability. In these cases, failure to obtain and document informed consent, failure to effectively communicate with the patient and family, and failure to assure followup and prompt assessment of complications are the factors that have most frequently led to litigation. Orthopaedic surgery ranks fifth among medical specialties in the total number of claims filed and also fifth in the cumulative amount of financial payments. Approximately 30% of filed cases ultimately result in some form of financial payment. The driving force behind litigation is financial gain for plaintiff's attorneys and compensation for plaintiffs. The motive is not the improvement of medical delivery systems or individual behavior. Access to useful data of a legal nature is extremely difficult. Only a small number of cases go on to a jury-based decision of public record. It is difficult to get accurate and complete information on the total number of cases filed, cases withdrawn, terms of settlements, and arbitrations because of the confidential nature of the settlement process.