Development and Validation of the Patient-Reported Submental Fat Rating Scale and the Patient-Reported Submental Fat Impact Scale.

BACKGROUND: No validated assessment tools are available to evaluate patient-reported outcomes specifically related to submental fat (SMF). OBJECTIVE: To develop and validate scales measuring the severity (Patient-Reported SMF Rating Scale [PR-SMFRS]) and psychological impact (Patient-Reported SMF Impact Scale [PR-SMFIS]) of SMF. MATERIALS AND METHODS: A literature review, content validation interviews (concept elicitation [n = 29] and cognitive debriefing [n = 15]) in adults with SMF, and expert interviews (n = 3) were conducted to develop the PR-SMFRS and PR-SMFIS. Psychometric validity (acceptability, reliability, and validity) for the PR-SMFRS and PR-SMFIS was assessed using data from 1 phase 2 and 5 phase 3 ATX-101 studies in patients with excess SMF. RESULTS: The PR-SMFRS was constructed as a single-item, 5-point rating of the SMF amount/size. The PR-SMFIS was constructed as a 6-item scale, with an 11-point numeric rating for each item. Both scales demonstrated acceptable psychometric properties (test-retest reliability and internal consistency). The anchor-based minimally important difference analysis suggests a 1-point improvement on the PR-SMFRS (scale of 0‒4) and a 3-point improvement on the PR-SMFIS (scale of 0‒10) represent clinically meaningful change. CONCLUSION: The PR-SMFRS and PR-SMFIS are reliable, valid instruments for assessing the severity and psychosocial impact, respectively, of SMF and detecting clinically meaningful change with intervention.

Safety of Laser-Assisted Delivery of Topical Poly-L-Lactic Acid in the Treatment of Upper Lip Rhytides: A Prospective, Rater-Blinded Study.

BACKGROUND: Perioral rhytides are a common complaint among dermatologic patients and can be notoriously stubborn and resistant to therapy. OBJECTIVE: We aimed to assess the safety of fractional ablative laser-assisted delivery of topical poly-L-lactic acid (PLLA) suspension in the treatment of upper cutaneous lip rhytides. MATERIALS AND METHODS: Prospective, single-arm, rater-blinded trial. Ten subjects with moderate to severe upper lip rhytides underwent 3 bimonthly treatments of low-density fractional carbon dioxide laser followed by topical application of PLLA suspension. Wrinkle severity before and after treatment was analyzed using computer-generated analyses. Blinded raters and subjects assessed improvement of wrinkles after treatment using the Global Aesthetic Improvement Scale (GAIS) (scores ranging from -3 to 3). Adverse events were recorded at each visit. RESULTS: Treatments were well tolerated. Other than expected post-laser erythema, no unanticipated adverse events were noted. After 3 treatments, the severity of upper lip wrinkles decreased by an average of 47% (p < .05) as calculated by computer-generated image analyses. Blinded raters and subjects rated wrinkles as much improved after 3 treatments (score of 2 on the GAIS). CONCLUSION: Laser-assisted delivery of PLLA is a safe and possibly effective treatment for upper lip rhytides.

A Double-Blind, Placebo-Controlled, Phase 3b Study of ATX-101 for Reduction of Mild or Extreme Submental Fat.

BACKGROUND: ATX-101 (deoxycholic acid injection) is approved for reduction of moderate or severe submental fat (SMF). OBJECTIVE: To evaluate the efficacy and safety of ATX-101 in subjects with mild or extreme SMF. PATIENTS AND METHODS: Adults with mild or extreme SMF (based on clinician assessment) were randomized to receive ≤6 treatments with ATX-101 or placebo. Efficacy end points, evaluated at 12 weeks after last treatment, included percentage of subjects who achieved ≥1-grade improvement in SMF from baseline based on both clinician and patient assessment (composite CR-1/PR-1 response) as well as multiple subject-reported outcomes. Safety end points included change in skin laxity and incidence of adverse events. RESULTS: Overall, 61.3% of ATX-101-treated subjects versus 6.7% of placebo-treated subjects with mild SMF and 89.3% versus 13.3% of subjects, respectively, with extreme SMF achieved a composite CR-1/PR-1 response (p < .001 for both). ATX-101-treated subjects also reported higher levels of satisfaction and greater reductions in the psychological impact of SMF versus placebo-treated subjects regardless of baseline SMF severity. Skin laxity was unchanged or improved in most of the subjects. Adverse events were mainly mild/moderate, transient, and associated with the injection site. CONCLUSION: ATX-101 was efficacious and well tolerated for reduction of mild or extreme SMF.

Management of Patient Experience With ATX-101 (Deoxycholic Acid Injection) for Reduction of Submental Fat.

BACKGROUND: ATX-101 (deoxycholic acid injection; Kythera Biopharmaceuticals, Inc., Westlake Village, CA [an affiliate of Allergan plc, Dublin, Ireland]) was recently approved for submental fat (SMF) reduction in the United States (Kybella) and Canada (Belkyra). The pivotal trials supporting these approvals revealed that ATX-101 is associated with common injection-site treatment reactions consistent with its mechanism of action and administration procedure. OBJECTIVE: The purpose of this study was to evaluate 4 patient experience management paradigms targeting the common injection-site adverse events of pain, swelling/edema, and bruising after a single treatment session with ATX-101. METHODS: In this double-blind, parallel-group, exploratory Phase 3b study (ClinicalTrials.gov identifier: NCT02007434), subjects with moderate to severe SMF were randomized 4:1 within each paradigm to receive ATX-101 2 mg/cm or placebo. In Paradigm 1, subjects received a cold pack application to the treatment area. In Paradigm 2, in addition to cold pack application, subjects were treated with topical lidocaine and injectable lidocaine containing epinephrine. In Paradigm 3, in addition to the interventions of Paradigm 2, subjects received loratadine and ibuprofen. Subjects in Paradigm 4 received the same interventions in Paradigm 3, plus application of a chin strap. RESULTS: Eighty-three subjects were treated. In ATX-101-treated subjects, peak pain occurred within 1 to 5 minutes of treatment, with median values at these time points ranging from 21.4 to 35.7 mm on a 100-mm pain visual analog scale ("mild"). Pain ratings reduced substantially by 15 minutes; at 4 hours after injection, pain was characterized as mild tenderness or mild achiness. Compared with cold alone, treatment with topical and injectable lidocaine reduced median peak pain by 17%. Addition of ibuprofen and loratadine resulted in a total reduction in pain by 40%. Peak swelling/edema in ATX-101-treated subjects was "modest," with mean values ≤1.7 (on a 0-5 scale) across all paradigms. Swelling/edema was not substantially mitigated by the interventions, including ibuprofen, loratidine, and the use of a chin strap. Bruising associated with ATX-101 treatment was confined to the treatment area, with mean values between 1.0 and 1.4 on a 0-to-5 scale. Bruising was modestly reduced by injectable lidocaine with epinephrine. CONCLUSION: Results from this study support the safety of ATX-101 for SMF reduction, and demonstrate that pain and bruising associated with ATX-101 treatment can be mitigated by a series of simple measures.

Review of the efficacy, durability, and safety data of two nonanimal stabilized hyaluronic acid fillers from a prospective, randomized, comparative, multicenter study.

BACKGROUND: Nonanimal stabilized hyaluronic acid (NASHA)-based fillers are currently the criterion standard for cosmetic soft tissue augmentation. OBJECTIVE: To report the efficacy, durability, and safety data of a large-particle NASHA filler and a small-particle NASHA filler. METHODS & MATERIALS: A blinded, prospective, randomized subject and evaluator study was conducted at 17 sites in the United States with 248 subjects enrolled. One of the two products was injected into both nasolabial folds and, if deemed necessary, the oral commissures of each subject. A 2-week touch-up injection was provided if necessary. Subjects returned for follow-up visits 2, 6, 12, and 24 weeks after receiving their last injection. Assessments were done using a subject diary, blinded investigator's Wrinkle Severity Rating Score (WSRS), and palpability of product. RESULTS: Both products demonstrated similar efficacy, durability, and safety profiles. CONCLUSION: Although both NASHA fillers demonstrated similar efficacy, durability, and safety, the fanning injection technique, and a faster rate of injection played a key role in the increase in incidence of adverse experiences. Furthermore, the safety of each NASHA product was demonstrated at volumes well beyond the volume range listed on the product inserts.

Effect of monopolar radiofrequency treatment over soft-tissue fillers in an animal model: part 2.

BACKGROUND AND OBJECTIVE: Monopolar radiofrequency (RF) treatment is used by physicians to heat skin and promote tissue tightening and contouring. Cosmetic fillers are used to soften deep facial lines and wrinkles. Patients who have had dermal fillers implanted may also benefit from or are candidates for monopolar RF skin tightening. This study examined the effect of RF treatment on various dermal filler substances. This is the second part of a two-part study. STUDY DESIGN/MATERIALS AND METHODS: A juvenile farm pig was injected with dermal fillers including cross-linked human collagen (Cosmoplast), polylactic acid (PLA) (Sculptra), liquid injectable silicone (Silikon 1000), calcium hydroxylapatite (CaHA) (Radiesse), and hyaluronic acid (Restylane). Skin injected with dermal fillers was RF-treated using a 1.5-cm2 treatment tip and treatment levels typically used in the clinical setting. Fillers were examined histologically 5 days, 2 weeks, or 1 month after treatment. Histological specimens were scored for inflammatory response, foreign body response, and fibrosis in order to assess the effect of treatment on early filler processes, such as inflammation and encapsulation. RESULTS: Each filler substance produced a characteristic inflammatory response. No immediate thermal effect of RF treatment was observed histologically. RF treatment resulted in statistically significant increases in the inflammatory, foreign body, and fibrotic responses associated with the filler substances. CONCLUSIONS: Monopolar RF treatment levels that are typically used in the clinical setting were employed in this animal study. RF treatment resulted in measurable and statistically significant histological changes associated with the various filler materials. Additional clinical and histological studies are required to determine the optimal timing of monopolar RF treatment and filler placement for maximal potential aesthetic outcome.

Low-level laser therapy for wound healing: mechanism and efficacy.

BACKGROUND: Given the recent interest in light-emitting diode (LED) photomodulation and minimally invasive nonablative laser therapies, it is timely to investigate reports that low-level laser therapy (LLLT) may have utility in wound healing. OBJECTIVES: To critically evaluate reported in vitro models and in vivo animal and human studies and to assess the qualitative and quantitative sufficiency of evidence for the efficacy of LLLT in promoting wound healing. METHOD: Literature review, 1965 to 2003. RESULTS: In examining the effects of LLLT on cell cultures in vitro, some articles report an increase in cell proliferation and collagen production using specific and somewhat arbitrary laser settings with the helium neon (HeNe) and gallium arsenide lasers, but none of the available studies address the mechanism, whether photothermal, photochemical, or photomechanical, whereby LLLT may be exerting its effect. Some studies, especially those using HeNe lasers, report improvements in surgical wound healing in a rodent model; however, these results have not been duplicated in animals such as pigs, which have skin that more closely resembles that of humans. In humans, beneficial effects on superficial wound healing found in small case series have not been replicated in larger studies. CONCLUSION: To better understand the utility of LLLT in cutaneous wound healing, good clinical studies that correlate cellular effects and biologic processes are needed. Future studies should be well-controlled investigations with rational selection of lasers and treatment parameters. In the absence of such studies, the literature does not appear to support widespread use of LLLT in wound healing at this time. Although applications of high-energy (10-100 W) lasers are well established with significant supportive literature and widespread use, conflicting studies in the literature have limited low-level laser therapy (LLLT) use in the United States to investigational use only. Yet LLLT is used clinically in many other areas, including Canada, Europe, and Asia, for the treatment of various neurologic, chiropractic, dental, and dermatologic disorders. To understand this discrepancy, it is useful to review the studies on LLLT that have, to date, precluded Food and Drug Administration approval of many such technologies in the United States. The fundamental question is whether there is sufficient evidence to support the use of LLLT.