Evaluation of the safety of a non-animal stabilized hyaluronic acid (NASHA – Q-Medical, Sweden) in European countries: a retrospective study from 1997 to 2001

BACKGROUND: In Europe, several filler devices are currently on the market for use in aesthetic dermatology and some of them cause severe, permanent, adverse reactions. Since 1996 a non-animal stabilized hyaluronic acid (NASHA) from Q-Medical, Sweden, has been introduced and is becoming a leading product in aesthetic dermatology. Hyaluronic acid has no species specificity and skin testing is not recommended before treatment. OBJECTIVE: Our purpose was to evaluate the incidence of adverse reactions from 1997 to 2001 and the safety of NASHA after injections into the skin for aesthetic reasons. METHOD: Surveys were sent to physicians in European countries that agreed to participate. This is a retrospective study. A total of 12 344 syringes were sold by the Q-Medical to these physicians and we evaluated the total number of patients treated to 35% of this number (4320). We separated immediate hypersensitivity reactions from delayed reactions and analysed infectious and other types of reactions. RESULTS: From 1997 until 2001, 34 cases of hypersensitivity were reported: 16 cases of immediate hypersensitivity and 18 cases of delayed. The global risk of sensitivity is 0.8%. Since 2000, the amount of protein in the raw product has decreased and the incidence of hypersensitivity reactions is around 0.6%. As 50% of these reactions are immediate and resolved within less than 3 weeks, the risk of strong but transient, delayed reaction is around 0.3%. Four cases of abscess were reported. They were all sterile. No bacterial infection was found. Herpetic recurrence is possible after lip augmentation according to the technique of injection. No systemic reactions were reported. CONCLUSION: NASHA is a very useful and safe filler product. Skin testing does not seem to be necessary.     

Magnetic resonance imaging to evaluate NASHA/Dx gel (Zuidex) for stress urinary incontinence

The Zuidex system for the treatment of stress urinary incontinence consists of non-animal stabilised hyaluronic acid/dextranomer (NASHA/Dx) gel and a precision guide, the Implacer. Whether the Implacer accurately deposits NASHA/Dx gel in the desired location within the urethral wall was investigated by magnetic resonance imaging (MRI), performed at a mean of 35 days post-treatment. Three or more deposits were observed in 11 of 16 patients (68.8%), with 39 of the 50 deposits clearly located within the urethral wall, as intended. Fourteen of 16 patients (87.5%) demonstrated improvement in their incontinence at 3 months, sustained at 12 months in 13 patients. No significant correlations between total implant volume and improvements in incontinence were observed at 3 months (p > or = 0.16) and 12 months (p > or = 0.30). In conclusion, accurate placement of NASHA/Dx gel into the desired location within the urethral wall was achieved in the majority of cases using the Implacer device, without endoscopic guidance.     

Complications and management of breast enhancement using hyaluronic acid

The authors report on their experience with using hyaluronic acid of non-animal origin manufactured using commercially available technology (Macrolane, Q-Med AB, Sweden) for breast enhancement in 4000 women treated since 2004 and describe the most common complications and their successful treatment. On average, 30 mL to 40 mL of Macrolane was injected into each breast. Of 274 women who returned to the clinic during 2007, <10% experienced local adverse events (eg, gel dislocation, Macrolane nodules and rare cases of infection). There were no serious systemic events and treatment was well tolerated. To prevent local complications, such as infection, an aseptic injection technique was required and early treatment of adverse events is recommended. While only small volumes of Macrolane were injected, it is comparatively easy and safe to perform breast enhancement of up to one cup size to correct asymmetry between breasts and to create fullness in the upper portion of the breast.     

Treatment of stress urinary incontinence using a copolymer system: impact on quality of life

OBJECTIVE: To investigate the effect on quality of life (QoL) of a novel system for treatment of stress urinary incontinence (SUI). PATIENTS AND METHODS: In an open, prospective, multicentre study, 42 women not previously treated by invasive therapy and with urodynamically verified SUI received 4 x 1.0 mL or 4 x 0.7 mL of non-animal stabilized hyaluronic acid/dextranomer copolymer injected transurethrally into the urethra via the Implacer device (Zuidex system, Q-Med AB, Uppsala, Sweden). QoL was assessed using the King's Health Questionnaire. The patients' perception of treatment benefit and the number of incontinence episodes/24 h were also investigated. RESULTS: There were significant improvements over baseline in seven of 10 domains of the King's Health Questionnaire at 3 months, and these improvements were sustained at 1 year. For the change from baseline to 1 year, eight of 10 domains showed a significant positive correlation with the number of incontinence episodes/24 h. In terms of treatment benefit, most of the women perceived an improvement at 1, 3, 6 and 12 months. Of the 18 women requiring re-treatment, most perceived an improvement at 3, 6 and 12 months. CONCLUSION: Treatment with the Zuidex system produced significant improvements over a year in both subjective QoL and objective incontinence measures, with a significant positive correlation between them.     

Three-Year Cost-effectiveness Model for Non–Animal Stabilized Hyaluronic Acid and Dextranomer Copolymer Compared With Sacral Nerve Stimulation After Conservative Therapy for the Management of Fecal Incontinence

Background

Two new therapies for fecal incontinence (FI) are now available: non–animal stabilized hyaluronic acid and dextranomer copolymer (NASHA/Dx) and sacral nerve stimulation (SNS).

Purpose

This study aimed to determine the cost-effectiveness of NASHA/Dx compared with SNS and conservative therapy (CT) for the treatment of FI after CT failure.

Methods

Decision tree models with Markov subbranches were developed to compare all direct costs and outcomes during a 3-year period from the viewpoint of the US third-party payer. Costs (in 2013 US dollars) of devices, medical and surgical care, and hospitalization were included. Outcomes included quality-adjusted life-years (QALYs) and incontinence-free days (IFDs). Both costs and outcomes were discounted at an annual rate of 3%. The incremental cost-effectiveness ratio was calculated for each outcome. One-way and probabilistic sensitivity analyses were performed to examine robustness of results and model stability. A budget impact analysis was also undertaken to estimate the potential cost and savings of NASHA/Dx for a payer with 1,000,000 covered lives.

Results

For the 3-year cost-effectiveness models, the expected cost was $9053 for CT, $14,962 for NASHA/Dx, and $33,201 for SNS. The numbers of QALYs were 1.769, 1.929, and 2.004, respectively. The numbers of IFDs were 128.8, 267.6, and 514.8, respectively. The incremental cost-effectiveness ratios per additional IFD gained were $42.60 for NASHA/Dx vs CT, $73.76 for SNS vs NASHA/Dx, and $62.55 for SNS vs CT. The incremental costs per QALY gained were $37,036 for NASHA/Dx vs CT, $244,509 for SNS vs NASHA/Dx, and $103,066 for SNS vs CT. The budget impact analysis evaluated the financial effect on the health care system of the use of NASHA/Dx and SNS. For the scenarios evaluated, when all of the patients receive NASHA/Dx, the net annual effect to the health care payer budget ranged from $571,455 to $2,857,275. When all of the patients receive SNS, the net annual effect to the health care payer budget ranged from $1,959,323 to $9,796,613.

Conclusion

Both NASHA/Dx and SNS have produced significant improvements in FI symptoms for affected patients. NASHA/Dx is a cost-effective and more efficient use of resources for the treatment of FI when compared with SNS. The budget impact analysis suggests that although reimbursement for NASHA/Dx treatment initially adds costs to the health care system, it is significantly less expensive than SNS for patients who are candidates for either treatment.     

Study of biomaterial-induced macrophage activation, cell-mediated immune response and molecular oxidative damage in patients with dermal bioimplants

Several soft-tissue dermal fillers have been reported to provoke immunogenicity and may cause adverse reactions despite claims regarding their safety. This study aimed to assess biomaterial-induced macrophage activation, cell-mediated immune response and oxidative stress in 169 patients with dermal bioimplants. To this end, we analysed plasma concentrations of myeloperoxidase (MPO), the chitinase-like proteins chitotriosidase and YKL-40 and molecular oxidative damage. The present study shows, for the first time, that the components of innate immunity: chitotriosidase and YKL-40, are significantly higher in patients with certain bioimplants and these markers of monocyte/macrophage activation rose progressively as adverse reactions (AR) evolved. Plasma MPO levels increased 4-fold in filler users with AR and 3-fold in those without. Analysis by filler type showed subjects injected with calcium hydroxylapatite, methacrylate, acrylamides and silicone to have values significantly above those of non-filler subjects for at least two plasma biomarkers, probably because the afore-mentioned biomaterials are permanent and prone to trigger AR in the long term. By contrast, hyaluronic acid alone elicited little immune response. Plasma concentrations of markers of oxidative damage to lipids and proteins were found to be significantly higher in users of four of the nine dermal fillers studied. These diffusible products of molecular peroxidation would stem from the reaction catalysed by MPO that generates potent oxidants, leading to cell oxidative damage which, in turn, may exert deleterious effects on the organism. Overall, the results of this study on the effects of a range of dermal fillers point to chronic activation of the immune response mediated by macrophages and PMNs. The increases in plasma of MPO, chitotriosidase and YKL-40 proteins and products of macromolecular peroxidation suggests that these molecules could serve as blood-based biochemical markers and alert to the risk of chronic immune system activation and development of adverse events that may arise from the use of certain bioimplants.     

Intra-peritoneal administration of paclitaxel with non-animal stabilized hyaluronic acid as a vehicle--a new strategy against peritoneal dissemination of gastric cancer

Background and aim: Intra-peritoneal administration (i.p.) of Taxanes has recently been reported to be effective for the treatment of peritoneal dissemination, presumably because extremely high concentration of the drug is achievable onto the disseminated nodules as compared to intra-venous administration. Here, we aimed to investigate the ability of non-animal stabilized hyaluronic acid (NASHA) to retain the anti-cancer drugs in the peritoneal cavity, and, consequently, improve the efficacy of i.p. administration of paclitaxel.