Efficacy of dextranomer in stabilised hyaluronic acid for treatment of faecal incontinence: a randomised, sham-controlled trial. Efficacy and safety of a single intra-articular injection of non-animal stabilized hyaluronic acid (NASHA) in patients with osteoarthritis of the knee. Dextranomer/hyaluronic acid copolymer implantation for vesico-ureteral reflux: a randomized comparison with antibiotic prophylaxis. A randomized trial of acidified nitrite cream in the treatment of tinea pedis. Use of sodium hyaluronate in treating temporomandibular joint disorders: a randomized, double-blind, placebo-controlled clinical trial. An evaluation of Hyalofill-F plus compression bandaging in the treatment of chronic venous ulcers. Treatment of psoriasis with topical NG-monomethyl-L-arginine, an inhibitor of nitric oxide synthesis. Failure of intraperitoneal adjuncts to improve the outcome of pelvic operations in young women. Efficacy and safety of intraarticular sodium hyaluronate in knee osteoarthritis. ORTHOVISC Study Group.
Injection of a bulking agent in the anal canal is an increasingly used treatment for faecal incontinence, but efficacy has not been shown in a controlled trial. We aimed to assess the efficacy of injection of dextranomer in stabilised hyaluronic acid (NASHA Dx) for treatment of faecal incontinence.
                In this randomised, double-blind, sham-controlled trial, patients aged 18-75 years from centres in USA and Europe were randomly assigned (2:1) to receive either transanal submucosal injections of NASHA Dx or sham injections. Randomisation was stratified by sex and region in blocks of six, and managed with a computer generated, real-time, web-based system. Patients and investigators were masked to assignment for 6 months when the effect on severity of faecal incontinence and quality of life was assessed with a 2-week diary and clinical assessments. The primary endpoint was response to treatment based on the number of incontinence episodes. A response to treatment was defined as a reduction in number of episodes by 50% or more. Patients in the active treatment group are still being followed up. This trial was registered with ClinicalTrials.gov, number NCT00605826.
                278 patients were screened for inclusion, of whom 206 were randomised assigned to receive NASHA Dx (n=136) or sham treatment (n=70). 71 patients who received NASHA Dx (52%) had a 50% or more reduction in the number of incontinence episode, compared with 22 patients who received sham treatment (31%; odds ratio 2·36, 95% CI 1·24-4·47, p=0·0089). We recorded 128 treatment-related adverse events, of which two were serious (1 rectal abscess and 1 prostatic abscess).
                Anal injection of NASHA Dx is an effective treatment for faecal incontinence. A refinement of selection criteria for patients, optimum injected dose, ideal site of injection, and long-term results might further increase the acceptance of this minimally invasive treatment.
                Q-Med AB.
                Copyright © 2011 Elsevier Ltd. All rights reserved. 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.
                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.
                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.
                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. Dextranomer/hyaluronic acid (Dx/HA) copolymer has favorable properties for endoscopic treatment of vesico-ureteral reflux (VUR). This open, randomized study was performed to compare the efficacy and safety of Dx/HA copolymer with antibiotic prophylaxis in children with VUR.
                Children >1 year of age with VUR grade II to IV (confirmed by voiding cysto-urethrogram) received endoscopic treatment with Dx/HA copolymer (n = 40) or 12 months of antibiotic prophylaxis (n = 21). Patients in the latter group with reflux grade >or=II at month 3 received a second implantation. All patients were reassessed by voiding cysto-urethrogram at month 12. Scintigraphy and ultrasound were performed to investigate renal status.
                At month 12, 69% of patients in the Dx/HA copolymer group had reflux grade <or=I bilaterally, compared with 38% in the antibiotic group (P =.029). Of patients with reflux grade <or=I at month 3, 89% showed a sustained response at month 12. One serious adverse event was reported in the antibiotic prophylaxis group, but this was not attributed to study treatment. No other adverse events occurred.
                Endoscopic treatment with Dx/HA copolymer was more effective than antibiotic prophylaxis in alleviating childhood VUR, and there were no safety concerns with either treatment. Nitric oxide is continually released from normal skin and has antimicrobial effects. An acidified nitrite cream releases supraphysiologic concentrations of nitric oxide and is fungicidal in vitro.
                The purpose of this study was to assess the efficacy of an acidified nitrite cream as treatment for tinea pedis.
                Sixty patients were recruited with both a clinical diagnosis of tinea pedis and hyphae identified on direct microscopy; they were randomly placed into an active group treated with twice-daily application of a mixture of 3% salicylic acid in aqueous cream and 3% nitrite in aqueous cream for 4 weeks and a control group treated with 3% salicylic acid in aqueous cream and aqueous cream alone. Nineteen patients completed the trial in the active group and 16 patients in the control group. Mycologic cure (negative results on microscopy and culture) and clinical improvement were measured at 0, 2, and 4 weeks and after a 2-week interval with no treatment.
                At the end of the treatment period, 18 of the 19 patients in the active group were mycologically cured as were 11 of 16 in the control group (p = 0.042). Two weeks after the cessation of treatment, 13 of 19 patients in the active group were mycologically cured and 5 of 16 in the control group (p = 0.028). The initial clinical scores in the active and control groups were 8.1 and 8.19 (two-tailed p = 0.95). At 4 weeks they were 1.66 and 6.0 (two-tailed p = 0.002) and after 2 weeks with no treatment 1.45 and 7.4 (two-tailed p < 0.0002).
                Acidified nitrite is effective therapy for tinea pedis. This study assessed the efficacy of high-molecular-weight sodium hyaluronate as a treatment for certain intracapsular temporomandibular joint (TMJ) disorders. One hundred twenty-one patients were studied at three test sites using a randomized, double-blind, placebo-controlled experimental design. Patients were selected on the basis of 1) confirmed diagnosis of either degenerative joint disease (DJD), reducing displaced disc (DDR), or nonreducing displaced disc (DDN); 2) nonresponsiveness to nonsurgical therapies; and 3) severe dysfunction as established by the Helkimo indices (HI), visual analog scales (VASs), and physical measurements of joint movement and joint noise (arthrophonometry [APM]). Subjects received a unilateral upper joint space injection of either 1) 1% sodium hyaluronate in physiologic saline (MedChem Products, Woburn, MA) or 2) USP physiologic saline. Clinical evaluations were performed using HI, VAS, and APM at weekly intervals for the first month and then at monthly intervals up to 6 months postinjection. Statistical analyses for both categorical and continuous variables were performed for each diagnostic category at each examination interval. For DJD, no difference in outcome was seen between treatment groups. For DDN, significant between-group differences were seen through 1 month; however, beyond this time point, the number of DDN patients was insufficient to draw meaningful conclusions concerning efficacy. For DDR, statistically significant within-group and between-group improvement in all three measures (HI, VAS, APM) was seen for the hyaluronate group compared to the saline group throughout the 6-month test period. At the month-2 and month-3 examination intervals, twice as many patients treated with hyaluronate (90%) showed improvement compared to patients given placebo. Further, only 3% of patients with DDR who were treated with hyaluronate relapsed compared with 31% of patients with DDR given placebo. Hyaluronan, a component of the extracellular matrix, plays a significant role in several aspects of tissue repair and the wound healing process.
                In this Italian study Hyalofill-F, a partial benzyl ester derivative of hyaluronan, used in combination with compression bandaging, was compared with the well-established therapy in Italy of non-adherent gauze plus compression therapy in the treatment of chronic venous leg ulcers.
                Hyalofill-F plus compression bandaging performed significantly better than non-adherent gauze plus compression bandage in all of the clinically relevant efficacy parameters. Mean reduction in ulcer area in the hyaluronan-derivative group was 8.1 cm2 after eight weeks of treatment, compared with 0.4 cm2 in the comparator group. The resulting difference of 7.7 cm2 between the two groups was statistically significant (p = 0.0019). Furthermore, statistically significant results in favour of the hyaluronan-derivative group were obtained in the following: speed of epithelialisation; leveling of the margins; degree of maceration; pain intensity and frequency.
                Hyalofill-F plus compression bandaging resulted in an earlier and greater decrease in ulcer area compared with non-adherent gauze plus compression bandaging, therapy supporting its use in the treatment of chronic venous ulcers. A double blind left, right comparative study was carried out in 17 psoriatic subjects to examine the influence of a topically applied inhibitor of nitric oxide (NO) synthesis on the pathogenic events of psoriasis. The inhibitor NG-monomethyl-L-arginine (L-NMMA) in aqueous cream BP was applied to one plaque while aqueous cream BP alone served as control. Compared with the control, the L-NMMA-treated side showed significant (77%) inhibition of NO production and a reduction in blood flow, confirming its bioavailability. L-NMMA significantly reduced staining for endothelial cells and intercellular adhesion molecule 1, while CD1a-positive Langerhans cells and CD8-positive suppressor cytotoxic T cells increased. CD4-positive lymphocytes and epidermal proliferation, as indicated by Ki-67 staining, were unaffected by this degree of inhibition of NO synthesis, and correspondingly significant clinical improvement was not found. An examination was made of the possibility that 100 to 200 ml of intraperitoneal 32% dextran 70 and/or 0.5% hydrocortisone sodium succinate (randomized independently with similar volumes of Ringer's lactate solution) might help to lessen the postoperative formation of adhesions among patients undergoing surgical procedures for peritubal adhesions (n = 76), endometriosis (n = 27), or midtubal occlusion (n = 61). Patients in the first two groups who were given intraperitoneal corticosteroids were also given systemic steroids. Nonparametric comparison of median adhesion scores at operation and at subsequent laparoscopy showed that there was a poorer outcome with dextran than when dextran was not used in every subgroup except one (repeat salpingolysis after previous operation for adhesions), including first operations for adnexal adhesions (Mann-Whitney U = 200, m = 23, n = 26; p less than 0.05). The probability was small (p beta less than 0.002) that an important beneficial effect of dextran was overlooked. Systemic corticosteroids were associated with a consistent trend toward improved outcome, especially in patients who initially had few or no adhesions, such as those operated on for endometriosis (U = 2, m = 7, n = 4; p less than 0.025), but among patients with tubal resections and anastomoses with adnexal adhesions the use of intraperitoneal hydrocortisone alone was associated with a worse outcome (U = 15, m = 12, n = 8; p less than 0.02). Life-table analysis of the accumulating probability of pregnancy showed that no significant difference resulted from adjunct use in any group. The conclusion is that no empiric basis supports the use of intraperitoneal 32% dextran 70 or 0.5% hydrocortisone in the attempt to prevent peritoneal adhesions, but further investigations on the systemic administration of corticosteroids to decrease the formation of adhesions would be useful. A prospective, multicenter, randomized, double-blind, controlled trial was conducted in 226 patients with knee osteoarthritis to evaluate the safety and efficacy of intraarticular injections of sodium hyaluronate. Patients were randomized to three weekly injections of 30 mg sodium hyaluronate or physiologic saline (control) and were observed for an additional 25 weeks. In comparison with the control group, among patients who completed at least 15 weeks of the study and whose Western Ontario and McMaster Universities Osteoarthritis Index pain score for the contralateral knee was less than 12 at baseline, sodium hyaluronate injection resulted in improvement in Western Ontario and McMaster Universities Osteoarthritis Index pain score, patient and investigator global assessments, and pain on standing from Weeks 7 to 27. Fifty-eight percent of patients treated with sodium hyaluronate achieved a 5-unit or greater improvement in mean pain score from Weeks 7 through 27, compared with 40% of control patients. In addition, nearly twice as many patients treated with sodium hyaluronate as with saline (30% versus 17%, respectively) achieved a net improvement of at least 7 units. In contrast to treatment with saline, Western Ontario and McMaster Universities Osteoarthritis Index pain score for the contralateral knee was inversely related to the magnitude of improvement after treatment with sodium hyaluronate. Few side effects were attributed to treatment, and no differences between treatment groups were seen in this respect (sodium hyaluronate, nine [8%]; saline, 11 [10%]). The incidence of injection site reactions was low (sodium hyaluronate, 1.2 %; saline, 1.5%). The results indicate that sodium hyaluronate treatment is well tolerated and produces statistically and clinically significant improvement of symptoms in patients with mild to moderate knee osteoarthritis in whom pain in the contralateral knee is relatively modest.
One large randomised controlled trial has shown that this form of treatment using dextranomer in stabilised hyaluronic acid (NASHA Dx) improves continence for a little over half of patients in the short term. However, the number of identified trials was limited and most had methodological weaknesses.