A Novel Mobile App-based Neuromuscular Electrical Stimulation Therapy for the Management of Knee Osteoarthritis: Results From an Extension Study of a Randomized, Double-blind, Sham-controlled, Multicenter Trial.

BACKGROUND: Mobile app-based neuromuscular electrical stimulation (NMES) is a promising treatment of knee osteoarthritis as previously demonstrated in a 12-week, randomized, double-blind, sham-controlled, multicenter trial (parent study). METHODS: Sixty-four of the 253 patients with knee osteoarthrosis who completed the 12-week parent study were enrolled in a 14-week extension study during which they continued to receive double-blind, home-based NMES (two 20-minute daily sessions, 5 d/wk) with either the original device ("active NMES") or a low-voltage version ("sham NMES"). All subjects who enrolled in the extension study comprised the intent-to-treat population and subjects who applied NMES (compliance monitored through the mobile app and a remote portal) for at least 2,800 minutes (14-week device usage) comprised the per-protocol therapy compliant population. RESULTS: In the per-protocol therapy compliant population, the active NMES group (n = 21) had a higher reduction in Visual Analog Scale Nominated Activity (64.7% versus 24.3%, P = 0.020) and Visual Analog Scale Nominated Activity improvement ≥50% (76.2% versus 12.5%, P = 0.002) than the sham NMES group (n = 8). Outcomes were not markedly different between groups in the intent-to-treat population. DISCUSSION: Applying NMES therapy for an additional 14 weeks (totaling 26 weeks) resulted in notable and clinically meaningful pain relief when patients were fully compliant with NMES.

A Novel Mobile App-Based Neuromuscular Electrical Stimulation Therapy for Improvement of Knee Pain, Stiffness, and Function in Knee Osteoarthritis: A Randomized Trial.

Background: Knee osteoarthritis (OA) is a widespread and debilitating disease that continues to plague patients. Over the past decade, neuromuscular electrical stimulation (NMES) therapy has shown promise in alleviating knee OA-related symptoms. This study sought to evaluate the efficacy and safety of a home-based NMES therapy for reduction of pain, stiffness, and function associated with knee OA. Material and methods: A randomized, sham-controlled, double-blind, multicenter trial was conducted with 12-week follow-up in 156 knee OA patients receiving either home-based NMES therapy or a modified low-voltage NMES therapy. Outcome measures including knee pain, stiffness, and functionality were collected at baseline through week 12 after the therapy. The primary endpoint was the percentage change from baseline (PCFB) in the Visual Analog Scale (VAS) pain for a patient-nominated physical activity. Secondary endpoints included VAS for general knee pain, Western Ontario and McMaster Universities Osteoarthritis Index, Knee Injury and Osteoarthritis Outcome Score Joint Replacement, and isometric quadriceps strength test. Results: A clinically meaningful reduction for VAS Nominated Activity was higher in the per-protocol treatment-compliant NMES group than that in the sham low-voltage NMES group at week 12 (PCFB of 42.8% vs 38.6%, P = .562). This was similarly true for the Western Ontario and McMaster Universities Osteoarthritis Index pain subscale (PCFBs of 36.8% vs 26.6%, P = .038). Similar trends and reductions of pain were observed for VAS General, Knee Injury and Osteoarthritis Outcome Score Joint Replacement Pain subscale, and isometric quadriceps strength. Conclusion: Home-based NMES treatment resulted in a clinically meaningful reduction of knee pain, stiffness, and knee functional improvements at week 12 compared with sham NMES treatment.

Efficacy and safety of fasinumab in patients with chronic low back pain: a phase II/III randomised clinical trial.

OBJECTIVES: To study the efficacy and safety of fasinumab in moderate-to-severe, chronic low back pain (CLBP). METHODS: In this phase II/III, double-blind, placebo-controlled study, patients with CLBP aged ≥35 years with inadequate pain relief/intolerance to acetaminophen, non-steroidal anti-inflammatory drugs and opioids were randomised to fasinumab 6 or 9 mg subcutaneous every 4 weeks (Q4W), 9 mg intravenous every 8 weeks (Q8W) or placebo. Primary endpoint was change from baseline to week 16 in average daily low back pain intensity (LBPI) numeric rating score. Key secondary efficacy variables included Roland-Morris Disability Questionnaire (RMDQ) and Patient Global Assessment (PGA). The results are based on a modified intent-to-treat analysis of 563/800 planned patients when enrolment was stopped early given emerging signals of joint risk in other osteoarthritis (OA) studies at doses being tested here. RESULTS: Significant placebo-adjusted LBPI reductions at week 16 were observed for fasinumab 9 mg Q4W and Q8W (least squares mean (standard error) -0.7 (0.3); both nominal p<0.05), but not 6 mg (-0.3 (0.3); p=0.39). RMDQ and PGA improvements to week 16 were greatest for fasinumab 9 mg intravenous. Numerically greater efficacy occurred in patients with, versus those without, peripheral OA (pOA) over 16 weeks. Treatment-emergent adverse events (AEs) occurred in 274/418 (65.6%) patients in the combined fasinumab groups and 94/140 (67.1%) placebo patients. Joint AEs, mostly rapid progressive OA type 1, were more frequent in the combined fasinumab groups (19 events in 16 patients (3.8%) vs 1 event in 1 patient (0.7%) for placebo); all except one occurred in pOA patients. CONCLUSIONS: Fasinumab highest doses, but not lower dose, improved both CLBP pain and function. Most joint AEs occurred in pOA patients, consistent with earlier findings in symptomatic OA. Further study is needed of patients with CLBP with and without pOA to determine optimal benefit-risk.

Assessing the Impact of a Novel Smartphone Application Compared With Standard Follow-Up on Mobility of Patients With Knee Osteoarthritis Following Treatment With Hylan G-F 20: A Randomized Controlled Trial.

BACKGROUND: Osteoarthritis (OA) is a leading cause of disability in the United States. Although no disease-modifying therapies exist, patients with knee OA who increase walking may reduce risk of functional limitations. OBJECTIVE: The objective of the study is to evaluate the impact of a mobile app (OA GO) plus wearable activity monitor/pedometer (Jawbone UP 24) used for 90 days on the mobility of patients with knee OA treated with hylan G-F 20. METHODS: Patients with knee OA aged 30 to 80 years who were eligible to receive hylan G-F 20 and were familiar with smartphone technology were enrolled in this randomized, multicenter, open-label study. Patients who had a body mass index above 35 kg/m2 were excluded. All patients received a single 6-mL injection of hylan G-F 20 and wore the Jawbone monitor. The patients were then randomized 1:1 to Jawbone and OA GO (Group A; n=107) with visible feedback (unblinded) or Jawbone only (Group B; n=104) with no visible feedback (blinded). The primary endpoint was mean change from baseline in steps per day at day 90 between Groups A and B. RESULTS: Baseline characteristics were similar between groups. There were significant differences between the increases in least squares (LS) mean number of steps per day (1199 vs 467, P=.03) and the mean percentage change (35.8% vs 11.5%, P=.02) from baseline in favor of Group A over Group B. There was a greater reduction in pain from baseline during the 6-minute walk test in Group A versus Group B. (LS mean change: -55.3 vs -33.8, P=.007). Most patients (65.4%) and surveys of physicians (67.3%) reported they would be likely or very likely to use/recommend the devices. Patient Activity Measure-13 scores improved from baseline (LS mean change for Groups A and B: 5.0 vs 6.9), with no significant differences between groups. The occurrence of adverse events was similar in the 2 groups. CONCLUSIONS: Use of a novel smartphone app in conjunction with a wearable activity monitor provided additional improvement on mobility parameters such as steps per day and pain with walking in the 6-minute walk test in patients with knee OA who were treated with hylan G-F 20. Results also highlight the amenability of patients and physicians to using mobile health technology in the treatment of OA and suggest further study is warranted.

Incorporating Novel Mobile Health Technologies Into Management of Knee Osteoarthritis in Patients Treated With Intra-Articular Hyaluronic Acid: Rationale and Protocol of a Randomized Controlled Trial.

BACKGROUND: Osteoarthritis (OA) of the knee is one of the leading causes of disability in the United States. One relatively new strategy that could be helpful in the management of OA is the use of mHealth technologies, as they can be used to increase physical activity and promote exercise, which are key components of knee OA management. OBJECTIVE: Currently, no published data on the use of a mHealth approach to comprehensively monitor physical activity in patients with OA are available, and similarly, no data on whether mHealth technologies can impact outcomes are available. Our objective is to evaluate the effectiveness of mHealth technology as part of a tailored, comprehensive management strategy for patients with knee OA. METHODS: The study will assess the impact of a smartphone app that integrates data from a wearable activity monitor (thereby both encouraging changes in mobility as well as tracking them) combined with education about the benefits of walking on patient mobility. The results from the intervention group will be compared with data from a control group of individuals who are given the same Arthritis Foundation literature regarding the benefits of walking and wearable activity monitors but who do not have access to the data from those monitors. Activity monitors will capture step count estimates and will compare those with patients' step goals, calories burned, and distance walked. Patients using the novel smartphone app will be able to enter information on their daily pain, mood, and sleep quality. The relationships among activity and pain, activity and mood, and sleep will be assessed, as will patient satisfaction with and adherence to the mobile app. RESULTS: We present information on an upcoming trial that will prospectively assess the ability of a mobile app to improve mobility for knee OA patients who are treated with intra-articular hyaluronic acid. CONCLUSIONS: We anticipate the results of this study will support the concept that mHealth technologies provide continuous, real-time feedback to patients with OA on their overall level of activity for a more proactive, personalized approach to treatment that may help modify behavior and assist with self-management through treatment support in the form of motivational messages and reminders.

Efficacy of platelet-rich plasma for chronic tennis elbow: a double-blind, prospective, multicenter, randomized controlled trial of 230 patients.

BACKGROUND: Elbow tenderness and pain with resisted wrist extension are common manifestations of lateral epicondylar tendinopathy, also known as tennis elbow. Previous studies have suggested platelet-rich plasma (PRP) to be a safe and effective therapy for tennis elbow. PURPOSE: To evaluate the clinical value of tendon needling with PRP in patients with chronic tennis elbow compared with an active control group. STUDY DESIGN: Randomized controlled trial; Level of evidence, 2. METHODS: A total of 230 patients with chronic lateral epicondylar tendinopathy were treated at 12 centers over 5 years. All patients had at least 3 months of symptoms and had failed conventional therapy. There were no differences in patients randomized to receive PRP (n = 116) or active controls (n = 114). The PRP was prepared from venous whole blood at the point of care and contained both concentrated platelets and leukocytes. After receiving a local anesthetic, all patients had their extensor tendons needled with or without PRP. Patients and investigators remained blinded to the treatment group throughout the study. A successful outcome was defined as 25% or greater improvement on the visual analog scale for pain. RESULTS: Patient outcomes were followed for up to 24 weeks. At 12 weeks (n = 192), the PRP-treated patients reported an improvement of 55.1% in their pain scores compared with 47.4% in the active control group (P = .163). At 24 weeks (n = 119), the PRP-treated patients reported an improvement of 71.5% in their pain scores compared with 56.1% in the control group (P = .019). The percentage of patients reporting significant elbow tenderness at 12 weeks was 37.4% in the PRP group versus 48.4% in the control group (P = .143). Success rates for patients at 12 weeks were 75.2% in the PRP group versus 65.9% in the control group (P = .104). At 24 weeks, 29.1% of the PRP-treated patients reported significant elbow tenderness versus 54.0% in the control group (P = .009). Success rates for patients with 24 weeks of follow-up were 83.9% in the PRP group compared with 68.3% in the control group (P = .037). No significant complications occurred in either group. CONCLUSION: No significant differences were found at 12 weeks in this study. At 24 weeks, however, clinically meaningful improvements were found in patients treated with leukocyte-enriched PRP compared with an active control group.

Intra-articular hylastan versus steroid for knee osteoarthritis.

PURPOSE: To assess the efficacy and safety of one and two intra-articular (IA) injections of the new viscosupplement, hylastan, compared with a single IA corticosteroid injection for pain due to knee osteoarthritis (OA). Hylastan is a high-molecular-weight hyaluronan derivative prepared from bacterial fermented sodium hyaluronate that was developed to remain in the joint for longer than most other viscosupplements. METHODS: This 6-month, double-blind, randomized, parallel group, multicenter trial enrolled patients aged ≥40 years who met American College of Rheumatology criteria for knee OA and had continued pain despite conservative treatment. Patients were randomized 1:1:1 to one of three arms: 2 × 4 mL hylastan (n = 129; arthrocentesis then IA hylastan Day 0, same treatment Week 2); 1 × 4 mL hylastan (n = 130; arthrocentesis then IA hylastan Day 0, arthrocentesis only Week 2); steroid (n = 132; arthrocentesis then IA methylprednisolone acetate 40 mg Day 0, arthrocentesis only Week 2). Participants and evaluators were blinded to treatment. The primary clinical outcome measure was change from baseline in WOMAC A pain score over all postbaseline visits to Week 26. RESULTS: Statistically significant pain reduction was observed in all three arms, with similar mean (95 % CI) changes in WOMAC A: 2 × 4 mL hylastan -0.9 (-1.0, -0.7); 1 × 4 mL hylastan -0.8 (-0.9, -0.7); steroid -0.9 (-1.0, -0.8); all P < 0.0001 versus baseline. Changes in secondary outcomes (OMERACT-OARSI and WOMAC A responder rates, patient/clinical observer global assessments, and WOMAC A1 walking pain) were similar in all three arms. Target knee adverse events were comparable for all treatments. CONCLUSIONS: Both IA hylastan injection regimens were effective in relieving pain with an acceptable safety profile. IA hylastan did not show a difference versus IA corticosteroid; therefore, the hypothesis of superior pain relief was not met. Further research is needed to compare the efficacy and safety of hylastan with other viscosupplements.

Efficacy and safety of collagenase clostridium histolyticum injection for Dupuytren contracture: short-term results from 2 open-label studies.

PURPOSE: The JOINT I (United States) and JOINT II (Australia and Europe) studies evaluated the efficacy and safety of collagenase clostridium histolyticum (CCH) injection for the treatment of Dupuytren contracture. METHODS: Both studies used identical open-label protocols. Patients with fixed-flexion contractures of metacarpophalangeal (MCP) (20° to 100°) or proximal interphalangeal (PIP) joints (20° to 80°) could receive up to three 0.58-mg CCH injections per cord (up to 5 total injections per patient). We performed standardized finger extension procedures to disrupt injected cords the next day, with follow-up 1, 2, 6, and 9 months thereafter. The primary end point (clinical success) was reduction in contracture to within 0° to 5° of full extension 30 days after the last injection. Clinical improvement was defined as 50% or more reduction from baseline contracture. RESULTS: Dupuytren cords affecting 879 joints (531 MCP and 348 PIP) in 587 patients were administered CCH injections at 14 U.S. and 20 Australian/European sites, with similar outcomes in both studies. Clinical success was achieved in 497 (57%) of treated joints using 1.2 ± 0.5 (mean ± SD) CCH injections per cord. More MCP than PIP joints achieved clinical success (70% and 37%, respectively) or clinical improvement (89% and 58%, respectively). Less severely contracted joints responded better than those more severely contracted. Mean change in contracture was 55° for MCP joints and 25° for PIP joints. With average contracture reductions of 73% and improvements in range of motion by 30°, most patients (92%) were "very satisfied" (71%) or "quite satisfied" (21%) with treatment. Physicians rated change from baseline as "very much improved" (47%) or "much improved" (35%). The CCH injections were well tolerated, causing no tendon ruptures or systemic reactions. CONCLUSIONS: Collagenase clostridium histolyticum was an effective, minimally invasive option for the treatment of Dupuytren contracture of a broad range of severities. Most treated joints (625 of 879) required a single injection. Treatment earlier in the course of disease provided improved outcomes. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic IV.

Novel drug OMS103HP reduces pain and improves joint motion and function for 90 days after arthroscopic meniscectomy.

PURPOSE: This phase 2 study compared OMS103HP (Omeros, Seattle, WA) with control (lactated Ringer's) irrigation solution in patients undergoing arthroscopic partial meniscectomy. METHODS: This was a prospective, multicenter, double-blind, randomized, vehicle-controlled, parallel-group study. Safety and postoperative pain, range of motion, and self-reported function were evaluated for 90 days. Statistical results were based on univariate analysis of variance and repeated-measures analyses. RESULTS: Mean visual analog scale (VAS) pain scores within 24 hours after discharge from the recovery room showed more pain in the control group beginning at 2 hours and peaking at 8 hours. Univariate analysis of variance of mean VAS scores over the 24-hour period did not meet statistical significance. Repeated-measures analysis yielded a statistically significant difference (P = .004) for time-by-treatment interaction, showing a clear drug benefit over time based on VAS scores. There were statistically significant differences at day 7 between the groups in passive flexion without pain (P = .022). The proportion of patients achieving flexion of 95° or greater, 110°, and 125° was greater for the OMS103HP group. The Knee Injury and Osteoarthritis Outcome Score (KOOS) showed statistically significant differences (P ≤ .05) between the OMS103HP and control groups for 4 of 5 outcomes (symptoms, pain, sport and recreation, and knee-based quality of life but not activities of daily living). All scores showed a treatment effect through day 90. The overall incidence of adverse events and abnormal laboratory values for the OMS103HP and control groups was similar. Serious adverse events occurred in 1 control patient. CONCLUSIONS: In this study of patients with meniscal tears who underwent simple debridement, the use of OMS103HP resulted in reduced acute postoperative pain (measured by VAS over the first 24 hours postoperatively), reduced pain during recovery (measured by the KOOS pain subscale, which measures both background levels of pain and exacerbations caused by movements or activities), improved postoperative knee motion, and improved functional outcomes as assessed with the KOOS Knee Survey. Clinical benefits of OMS103HP were consistent and sustained throughout 90 days of postoperative follow-up. LEVEL OF EVIDENCE: Level I, prospective, randomized, controlled trial.

The relationship between skeletal muscle serum markers and primary THA: a pilot study.

Various reports confirm elevations in serum markers associated with skeletal muscle injury after orthopaedic surgery in the absence of overt clinical manifestations of myocardial injury. We therefore measured the influence surgical approach has on these serum markers after primary THA. We nonrandomly enrolled 30 nonconsecutive patients undergoing THA in three groups of 10 based on current surgical approaches used at our facility: (1) minimally invasive (MIS) modified Watson Jones approach; (2) miniposterior transmuscular approach (MIS-I); and (3) MIS-II incision. Blood samples for hemoglobin, hematocrit, cardiac troponin I, total creatine kinase, creatine phosphokinase, and serum myoglobin were obtained the morning before surgery as a baseline, immediately postoperatively, and 72 hours thereafter. We found reproducible trends in serum enzyme levels consistent with skeletal muscle damage resulting from primary THA. Troponin I remained normal in all but one patient indicating no myocardial contribution to measured serum enzyme levels. All three procedures resulted in similar trends in serum enzyme markers relevant to primary THA. Our preliminary data suggest no surgical approach appears to affect the degree of muscle trauma more or less than another.