A randomized saline-controlled trial of NASHA hyaluronic acid for knee osteoarthritis.

OBJECTIVE: NASHA hyaluronic acid is administered as a single intra-articular injection to treat the symptoms of osteoarthritis (OA). In a previous trial, post-hoc analysis indicated that NASHA provides significantly greater pain relief than saline in patients with OA confined to the study knee. We aimed to evaluate the safety and efficacy of NASHA in patients with unilateral knee OA. RESEARCH DESIGN AND METHODS: This was a randomized, double-blind, saline-controlled trial. All patients had knee OA confirmed by American College of Rheumatology criteria and a WOMAC pain score of 7-17 in the study knee, but no pain in the previous 3 months in the non-study knee. Treatment comprised a single intra-articular injection of NASHA or saline control. The follow-up period was 6 weeks. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov NCT01806207. MAIN OUTCOME MEASURES: The primary efficacy endpoint was the responder rate, defined as the percentage of patients with ≥40% improvement from baseline in WOMAC pain score and an absolute improvement of ≥5 points. RESULTS: A total of 218 patients received study treatment (NASHA: 108, saline: 110). In the main intention-to-treat (ITT) analysis, no statistically significant difference in responder rate was found between the two groups at 6 weeks (NASHA: 30.6%; saline: 26.4%). A post-hoc subgroup analysis of patients without clinical effusion in the study knee at baseline showed a significantly higher 6 week responder rate with NASHA than with saline: 40.6% versus 19.7% (p = 0.0084). A total of 68 adverse events were reported among 44 patients in the NASHA group, compared with 69 adverse events among 44 patients in the saline group. The main weakness of the study was the short, 6 week follow-up duration. In addition, image guidance was not used to ensure injection as intended into the intra-articular space. CONCLUSIONS: Single-injection NASHA was well tolerated and, although there was no significant benefit versus saline control in the primary analysis, post-hoc analysis showed a statistically significant improvement in pain relief at 6 weeks among patients without clinical effusion at baseline.

A pain model with a neuropathic somatosensory lesion: Morton neuroma.

A randomized, double-blind, three-period cross-over study was performed to characterize the sensory phenotype and pain demographics in patients with Morton neuroma (n=27) and to explore the effects of local administration (2mL) of placebo and lidocaine (1 and 10mg/mL) around the neuroma. Using the pain quality assessment scale (PQAS), the highest rating was seen for unpleasant pain and intensity of deep pain and the lowest for sensitive skin. Ongoing pain was reported in 32% of patients. Patients reported mild to moderate average pain, and that pain had interfered with sleep only marginally. Quantitative sensory testing (QST) measurements in the innervation territory showed hypophenomena or hyperphenomena in all patients, indicating that all had neuropathy. There was no particular QST modality that appeared to be specifically affected. Even the high-dose lidocaine resulted in limited effects on nerve-impulse conduction as judged by the effect on QST variables. However, both doses of lidocaine significantly reduced pain after step-ups, compared to placebo, indicating that lidocaine in this setting affected predominantly impulse generation and not impulse conduction. Following placebo treatment, pain after step-ups was similar in patients with and without hyperalgesia, indicating that the presence of hyperalgesia does not affect the pain intensity evoked by step-ups or walking. This pain model in patients with Morton neuroma allows investigation of drugs in a cross-over design and provides an opportunity to explore drug effects on both pain and QST variables. Commonly, neuromas are surgically removed and can be characterized in depth in vitro, thereby allowing close links to be established between pathophysiology and drug effect.

A prospective randomized controlled trial of plantar versus dorsal incisions for operative treatment of primary Morton's neuroma.

BACKGROUND: There are a great number of studies on the outcome of surgery for Morton's neuroma. However, there is a lack of controlled trials to determine the outcome in general and for the 2 most used surgical approaches. This prospective and randomized trial studied the outcome and adverse events of resected primary Morton's neuromas, comparing plantar and dorsal incisions. METHODS: Seventy-six patients were randomized to treatment with either a plantar or a dorsal incision by 2 senior surgeons. Questionnaires were evaluated and physical examinations performed at baseline and at 3 and 12 months postoperatively by the treating surgeon and at a mean of 34 months (range, 28-42 months) by an independent surgeon. The follow-up rate was 93%. RESULTS: Histological examination of specimens verified resection of nerves in all cases except 1, which was in the dorsal group (artery). The main outcome variable, pain at daily activities, was significantly reduced by 96% (plantar) and 97% (dorsal) and restrictions in daily activities were reduced by 77% (plantar) and 67% (dorsal) at the final follow-up. Scar tenderness was noted by 3% (plantar) and 0% (dorsal) at the final evaluation. Clinically good results with surgery were noted in 87% (plantar) and 83% (dorsal) of cases. There were 5 complications in the plantar group and 6 in the dorsal group, with a difference in type of complications. CONCLUSIONS: This study demonstrated 87% (plantar) and 83% (dorsal) clinically good outcomes and no significant differences between the procedures in regard to pain, restrictions in daily activities, and scar tenderness. However, there was a difference between the groups in the type of complications. LEVEL OF EVIDENCE: Level I, prospective randomized trial.

A prospective 2-year follow-up study of plantar incisions in the treatment of primary intermetatarsal neuromas (Morton's neuroma).

BACKGROUND: The aim of this prospective study, with a mean 29 (minimum 24) months follow-up was to evaluate the outcome of surgical treatment with a longitudinal, plantar incision of primary Morton's neuromas. METHODS: All 55 patients (59 feet) had their pre-and post-operative pain assessed using VAS, and pre-operative radiographs evaluated. Two independent orthopedic surgeons performed the follow-up examinations. RESULTS: Histology confirmed positive neuromas in all cases and there were only three minor complications. There was 88% reduction of pain at follow-up and 86% of all patients rated the overall satisfaction with the results as excellent or good. For those patients engaged in sports activities, the corresponding figure was 93%. CONCLUSIONS: Surgery with a plantar incision seems to be a reliable and safe intervention of primary Morton's neuromas, with only limited number of minor complications and a subjective satisfactory outcome, well in accordance with other studies, using different, surgical approaches.

Plantar versus dorsal incision in the treatment of primary intermetatarsal Morton's neuroma.

BACKGROUND: Only few studies have compared plantar and dorsal incisions in the treatment of primary intermetatarsal Morton's neuroma (PIMN). The results and guidelines are, however, still controversial, mainly due to confounding factors and study design. The present study is an attempt to systematically compare the two approaches. MATERIALS AND METHODS: With a 2- to 5-year followup, we retrospectively compared the results of 125 patients (132 feet) with PIMN. All specimens had histology assessments. Longitudinal plantar incisions were performed by one experienced surgeon (n = 69) and dorsal incisions by another (n = 56). Records were reviewed, questionnaires evaluated, and physical examinations performed by one of two independent orthopaedic surgeons. RESULTS: Histology verified nerve resections in all specimens except in three cases of missed nerves in the dorsal group. There were significant differences, in favor of the plantar group, regarding long-term sensory loss, postoperative sick-leave weeks and complications. The clinical outcome regarding postoperative pain at followup and overall satisfaction rating were similar. CONCLUSION: We conclude that the two surgical approaches were comparable for clinical outcome and patient satisfaction at followup, whereas significant differences, in favor of plantar incisions, were present regarding residual sensory loss and number of complications. The more serious complication with the dorsal approach, missed neuroma, may result in an increased risk of failure with the dorsal incision.

Non-animal stabilized hyaluronic acid: a new formulation for the treatment of osteoarthritis.

Hyaluronic acid (HA) is a major component of human synovial fluid, providing the rheologic properties (elasticity and viscosity) that enable the synovial fluid to perform lubricating and shock-absorbing functions within the healthy joint. Over the last 2 decades, HA preparations have become established in intra-articular therapy of osteoarthritis (OA), particularly OA of the knee. Existing HA preparations, both cross-linked and non-cross-linked, are all administered by courses of multiple injections, and all have been associated with variable success rates. The clinical profile of an HA preparation is inextricably linked to the product's physicochemical properties. For example, the molecular structure of the HA affects the intra-articular residence time, which should in turn influence the duration of action post-injection. Non-animal stabilized hyaluronic acid (NASHA) is a new-generation HA preparation, produced wholly from non-animal sources. NASHA is stabilized using a carefully controlled cross-linking process, which increases the intra-articular residence time from hours to weeks. This facilitates single-injection treatment for OA without affecting the biocompatibility of HA. This review evaluates the properties of NASHA, including the available clinical data, in the context of previously developed HA preparations.

Efficacy and safety of a single intra-articular injection of non-animal stabilized hyaluronic acid (NASHA) in patients with osteoarthritis of the knee.

OBJECTIVE: Non-animal stabilized hyaluronic acid (NASHA) is a novel hyaluronan (HA) preparation with a 4-week intra-articular half-life. This study compared the efficacy of a single injection of NASHA with placebo in patients with osteoarthritis (OA) of the knee. DESIGN: This was a 26-week randomized, double-blind, multicenter study of a single intra-articular knee injection with either NASHA or placebo (saline). Assessments included the Western Ontario McMasters Universities osteoarthritis index (WOMAC, Likert Scale) and patients' overall global disease status. A positive response was defined as a reduction in WOMAC pain score for the study knee of 40% from baseline with a minimum improvement of > or =5 points. RESULTS: A total of 346 (NASHA 172; placebo 174) patients were treated. WOMAC scores and quality of life were improved in both the NASHA and placebo groups. For the overall population, there were no statistically significant between-group differences in response rates for any efficacy parameters. In patients with OA confined to the knee (N=216), a greater response to NASHA than placebo was observed at week 6 (P=0.025). There were few treatment-related events. CONCLUSIONS: NASHA was not superior to placebo for the primary efficacy analysis. However, these data may be confounded by the inclusion of patients with OA at other sites, as significant benefits over placebo were found among patients with OA confined to the knee. Future trials of OA that examine a local therapy might need to consider restricting the study population to those patients having OA of only the signal joint.