Multimodal Facial Aesthetic Treatment on the Appearance of Aging, Social Confidence, and Psychological Well-being: HARMONY Study.

BACKGROUND: A global approach to facial rejuvenation involves multiple treatment modalities. OBJECTIVES: The aim of this study was to evaluate the impact of multimodal facial aesthetic treatment on self-reported psychological and social outcomes. METHODS: HARMONY, a prospective, multicenter, 4-month study, enrolled patients aged 35 to 65 years to receive on-label treatment with a combination of hyaluronic fillers (VYC-20L, HYC-24L, and/or HYC-24L+), onabotulinumtoxinA, and bimatoprost. Fillers were injected on Day 1, with touch-ups performed on Day 14. OnabotulinumtoxinA was injected at Month 3 into glabellar lines and/or crow's feet lines. Patients applied bimatoprost to eyelashes once daily for 17 weeks. Mean change from baseline on FACE-Q Psychological Well-being and Social Confidence Scales, FACE-Q Aging Appearance Appraisal Scale, and FACE-Q Age Appraisal Visual Analog Scale were assessed. RESULTS: Of 100 patients treated, 93 were evaluated at 4 months posttreatment. Significant improvement vs baseline was observed on the FACE-Q Scales for Psychological Well-being (mean change, -19.9; P < 0.00001), Social Confidence (mean change, -18.2; P < 0.00001), and Aging Appearance (mean change, -28.5; P < 0.0001). On average, patients' self-assessed age was 0.1 years older than actual age at baseline and 4.5 years younger at Month 4 (P < 0.001 vs baseline). Forty-two patients experienced adverse events, all mild to moderate. CONCLUSIONS: Multimodal, full facial aesthetic treatment improves patients' self-reported psychological well-being, social confidence, aging appearance, and perceptions of chronologic age.

Impact of Comprehensive, Minimally Invasive, Multimodal Aesthetic Treatment on Satisfaction With Facial Appearance: The HARMONY Study.

BACKGROUND: Individuals seeking aesthetic treatment have concerns regarding multiple facial areas. OBJECTIVES: Assess the aesthetic impact and satisfaction achieved with a multimodal approach to aesthetic treatment using a combination of minimally invasive treatments. METHODS: Prospective, multicenter, rater-blinded, 4-month HARMONY study evaluated patient satisfaction and aesthetic impact of a combination of fillers (VYC-20L, HYC-24L, and HYC-24L+), onabotulinumtoxinA, and bimatoprost. Males and females aged 35 to 65 years received on-label, staged treatment with fillers, as needed per investigator assessment, on day 1, with touch ups allowed on day 14. Bimatoprost was self-administered once daily for 17 weeks. OnabotulinumtoxinA was injected into glabellar lines, crow's feet lines, or both at month 3. Primary effectiveness measure was mean change from baseline on the FACE-Q 10-item Satisfaction with Facial Appearance Overall Scale. RESULTS: Of 100 patients treated, 93 underwent at least the 4-month posttreatment assessment and were assessed for efficacy. The FACE-Q Satisfaction with Facial Appearance Overall Scale total score increased from baseline (41.2) to month 4 (72.9; P < 0.00001; effect size, 2.7). Improvement following multimodal treatment was observed on FACE-Q individual items. Self-perceived age decreased from 0.2 years older than actual age at baseline to 4.6 years younger at month 4. Nearly all patients (99%) rated themselves as improved or much improved on the Global Aesthetic Improvement Scale. Investigator assessments also demonstrated improvement. Mild to moderate adverse events occurred in 42 patients. CONCLUSIONS: Minimally invasive, multimodal treatment resulted in improvements in FACE-Q scores and perceived age, indicating a high degree of patient satisfaction and a younger facial appearance.

Combining Microfocused Ultrasound With Botulinum Toxin and Temporary and Semi-Permanent Dermal Fillers: Safety and Current Use.

BACKGROUND: A microfocused ultrasound system with visualization (MFU-V) is currently indicated for use as a noninvasive dermatological aesthetic treatment to lift the eyebrows, lax submental and neck tissue, and improve lines and wrinkles of the décolleté. OBJECTIVE: To determine the existence of any safety signals when combining MFU-V with botulinum toxin-A and/or semipermanent and temporary dermal fillers. MATERIALS AND METHODS: A retrospective chart review was performed using subjects who received aesthetic treatments including incobotulinumtoxinA injection, cohesive polydensified matrix hyaluronic acid (CPM HA) dermal fillers, and calcium hydroxylapatite (CaHA) dermal fillers within 6 months of treatment with MFU-V in the same or different anatomic areas. RESULTS: All subjects (N = 101; 96 female; 25-70 year old) received MFU-V, 18% received incobotulinumtoxinA injections, and 81% were treated with CPM HA and/or CaHA fillers. Seven adverse events (7%) were reported: bruising/purpura (n = 4), swelling (n = 1), paresthesia (n = 1), and herpes simplex virus (HSV) outbreak (n = 1). Only the HSV outbreak was considered to be related to combined treatments. CONCLUSION: Although limited by relatively few subjects, the results of the present study suggest that the safety profile of MFU-V combined with other aesthetic products is consistent with the safety profiles of the individual treatments.

A Comprehensive Approach to Multimodal Facial Aesthetic Treatment: Injection Techniques and Treatment Characteristics From the HARMONY Study.

BACKGROUND: The HARMONY study is the first clinical trial to assess the impact of a global approach to facial rejuvenation with several minimally invasive modalities, using patient-reported outcome measures. OBJECTIVE: Provide details of this treatment approach and describe investigators' experiences and recommendations based on this study. METHODS: This multicenter, 4-month study evaluated subject satisfaction with and psychological impact of combined treatment with VYC-20L (Juvéderm Voluma XC), HYC-24L (Juvéderm Ultra XC), HYC-24L+ (Juvéderm Ultra Plus XC), onabotulinumtoxinA (Botox), and bimatoprost 0.3% ophthalmic solution (Latisse). Treatment-naive adults with moderate-to-severe facial lines and folds and eyelash hypotrichosis received on-label, staged treatment with fillers. Bimatoprost was self-administered once daily for 17 weeks from day 1. OnabotulinumtoxinA was administered for glabellar lines, crow's feet lines, or both at month 3. RESULTS: Overall, 100 subjects received bimatoprost for eyelash hypotrichosis, 96 received onabotulinumtoxinA for glabellar lines and/or crow's feet lines, and 96 received VYC-20L for midface volume deficit. From 17 to 96 subjects received HYC-24L and/or HYC-24L+ for nasolabial folds, oral commissures, marionette lines, perioral lines, or radial cheek lines. Injections of filler generally progressed from cranial to caudal, with midface injected first. Investigator-reported factors that may have contributed to the potential benefits of this approach include the critical role of the midface in facial aesthetics, use of lower volumes of filler in individual facial areas, and anesthetic effects. CONCLUSION: The investigators' perspectives and experience with the injection pattern, sequencing, volumes, and techniques may provide valuable guidance for a multimodal approach to facial aesthetic treatment.

Dermatological Adverse Events Associated with Topical Brimonidine Gel 0.33% in Subjects with Erythema of Rosacea: A Retrospective Review of Clinical Studies.

BACKGROUND: The topical α2 adrenergic receptor agonist brimonidine gel 0.33% is an effective and safe pharmacological treatment for the facial erythema of rosacea. However, adverse events of worsened redness have occasionally been reported with its use. OBJECTIVE: A detailed analysis of adverse events is needed to accurately define worsening erythema and the adverse-events profile associated with brimonidine gel treatment. METHODS AND MEASUREMENTS: A retrospective review of related dermatological adverse events occurring in subjects enrolled in the two pivotal four-week Phase 3 studies and the 52-week long-term safety study for brimonidine gel was conducted. Measurements included total adverse-event incidences; number of subjects experiencing adverse events; study discontinuation due to adverse events, severity, onset, episodic duration period; and correlation of adverse events to subject disposition, and rosacea profile. RESULTS: Flushing and erythema were the most commonly reported adverse events, occurring in a total of 5.4 percent of subjects in the Phase 3 studies and in 15.4 percent in the long-term study. Most adverse events were mild or moderate in severity, transient, and intermittent. Adverse events occurred early in treatment, and duration was short-lived in the majority of cases. Adverse-event patterns were not remarkably altered with regard to subject disposition in the long-term study. CONCLUSION: Adverse events of worsening redness are not frequent, are transient in nature, and occur early in the course of treatment with brimonidine gel.

Development and validation of a photographic scale for assessment of lip fullness.

BACKGROUND: As lip augmentation becomes more popular, validated measures of lip fullness for quantification of outcomes are needed. OBJECTIVE: Develop a scale for rating lip fullness and establish its reliability and sensitivity for assessing clinically meaningful differences. METHODS: The initial Allergan Lip Fullness Scale (iLFS; a four-point photographic scale with verbal descriptions) was validated by eight physicians rating 55 live subjects during two rounds, conducted on one day. In addition, subjects performed self-evaluations. The revised Allergan Lip Fullness Scale (LFS), a five-point scale with a broader range of lip presentations, was validated by 21 clinicians in two online image rating sessions, ≥14 days apart, in which they used the LFS to rate overall, upper, and lower lip fullness of 144 3-dimensional (3D) images. Physician inter- and intra-rater agreement, subject intra-rater agreement (iLFS), and subject-physician agreement (iLFS) were evaluated. Additionally, during online rating session 1, raters ranked 38 pairs of 3D images, taken before and after lip augmentation, as "clinically different" or "not clinically different." The median LFS score difference for clinically different pairs was calculated to determine the clinically meaningful difference. RESULTS: Clinician inter- and intra-rater agreement for the iLFS and LFS was substantial to almost perfect. Subject self-assessments (iLFS) had substantial intra-rater reliability and a high level of agreement with physician assessments. Median LFS score differences for overall, upper, and lower lip fullness were 1 (mean: 0.63-0.69) for "clinically different" and 0 (mean: 0.28-0.36) for "not clinically different" image pairs; thus, clinical significance of a 1-point difference in LFS score was established. CONCLUSIONS: The LFS is a reliable instrument for physician classification of lip fullness. A 1-point score difference can detect clinically meaningful differences in lip fullness.

Enhanced efficacy of a facial hydrating serum in subjects with normal or self-perceived dry skin.

OBJECTIVE: To evaluate the efficacy and tolerance of a facial hydrating serum when added to a moisturizer regimen compared to a moisturizer regimen alone. DESIGN: Evaluator-blinded, single-center, clinical study with investigator assessments at Baseline and Week 2. TREATMENT: After washing with a facial cleanser in the morning and evening, subjects either applied the hydrating serum to their face followed by application of the moisturizer or applied only a moisturizer. PARTICIPANTS: Thirty-two women, aged 25 to 55 years with Fitzpatrick skin types I to V and normal or self-perceived dry skin completed the study. Seventeen subjects (Group 1) aged 25 to 51 years were randomly assigned to receive the facial hydrating serum in addition to a moisturizer regimen, whereas 15 subjects (Group 2) aged 34 to 55 years, were randomized to receive the moisturizer regimen alone. MEASUREMENTS: Visual grading of the condition of the facial skin with regard to dryness, tactile roughness and softness, rating of irritation (subjective and objective), and digital photography. A self-assessment questionnaire was also employed to assess patient satisfaction. RESULTS: Clinical assessments by the investigator showed statistically significant improvements (P<0.02) in facial skin parameters (reduction in dryness and increased skin softness) after two weeks of combined use of the hydrating serum and moisturizer compared to the group who used moisturizer alone. No adverse events were reported during the course of the study. CONCLUSION: The results from a two-week clinical study demonstrate that this facial hydrating serum was well tolerated and effective in improving facial dry skin parameters beyond that obtained with a moisturizer alone.

Randomized, double-blind, double-dummy, vehicle-controlled study of ingenol mebutate gel 0.025% and 0.05% for actinic keratosis.

BACKGROUND: There is a need for improved medical approaches to the treatment of actinic keratosis. Ingenol mebutate, a diterpene ester extracted and purified from the plant Euphorbia peplus, is being evaluated as a topical therapy for actinic keratosis. OBJECTIVE: Assess the efficacy and safety of ingenol mebutate (formerly PEP005) gel at 3 dosing regimens for the treatment of actinic keratosis. METHODS: Patients with non-facial actinic keratoses applied vehicle gel for 3 days, ingenol mebutate gel, 0.025% for 3 days, or ingenol mebutate gel, 0.05% for 2 or 3 days, with an 8-week follow-up period. RESULTS: All 3 active treatments were significantly more effective than vehicle at clearing actinic keratosis lesions, with a dose response observed. The partial clearance rate (primary efficacy end point) for patients treated with ingenol mebutate gel ranged from 56.0% to 75.4% compared with 21.7% for vehicle gel (P = .0002 to P < .0001 vs vehicle). The complete clearance rate was also significantly higher (P < or = .0006) for patients in the ingenol mebutate gel treatment groups (range: 40.0% to 54.4%) compared with vehicle (11.7%), as was the baseline clearance rate (range: 42.0% to 57.9% for ingenol mebutate gel compared with 13.3% for vehicle, P < .0001 to .0007 vs vehicle). The median percentage reduction in baseline actinic keratosis lesions for patients treated with ingenol mebutate gel ranged from 75% to 100% compared with 0% for vehicle gel (P < .0001 vs vehicle). Active treatment was well tolerated at all dosages. The mechanism of action of this agent is the localized induction of necrosis followed by a transient inflammatory response, and this was manifested in most patients as transient local skin responses consisting primarily of erythema, flaking/scaling, and crusting. There was no evidence of treatment-related scarring. LIMITATIONS: Local skin responses may have suggested active treatment to investigators. CONCLUSIONS: Short-course, field-directed therapy with ingenol mebutate gel for actinic keratoses on non-facial sites seems to be effective with a favorable safety profile and potential benefits over topical agents that require a more prolonged course of treatment.

Patient-reported outcomes with botulinum toxin type A treatment of glabellar rhytids: a double-blind, randomized, placebo-controlled study.

BACKGROUND: Global patient-reported outcomes do not evaluate specific aspects of treatment that are important to patients. OBJECTIVE: The objective was to evaluate self-perception of age and specific outcomes that are important to patients receiving botulinum toxin type A or placebo for moderate to severe glabellar lines (using the Facial Line Outcomes Questionnaire to assess how much facial lines bother them, make them look older, detract from their facial appearance, prevent a smooth facial appearance, and make them look tired, stressed, or angry). METHODS AND MATERIALS: In the double-blind phase of this 12-week study, 70 patients were randomly assigned to treatment with 20 U botulinum toxin type A (BOTOX Cosmetic) or placebo. At Week 4, those still with moderate or severe glabellar lines were offered open-label 20 U botulinum toxin type A. RESULTS: Median glabellar line severity was significantly lower after botulinum toxin treatment than after placebo. Compared with placebo, botulinum toxin also resulted in significantly superior patient assessments and a greater proportion of patients considering they looked younger than their current age. CONCLUSIONS: Botulinum toxin type A can achieve specific goals of treatment that are important to patients and help them feel that they look younger than their current age.

Assessing treatment outcomes in toenail onychomycosis clinical trials.

Several oral and topical medications are available for the treatment of onychomycosis, a widespread fungal infection of the nail. Since efficacy criteria vary greatly among clinical trials for onychomycosis treatment, it is difficult for physicians to compare outcomes and determine the appropriate therapy for a given patient. The present analysis evaluates the efficacy criteria used in intention-to-treat clinical trials of itraconazole, terbinafine, and 8% ciclopirox nail lacquer, drugs approved by the US FDA for the treatment of onychomycosis. Efficacy parameters often appear to use subjective assessment tools and may not include the actual size measurement of the affected target nail as an efficacy variable. Parameters, which assess both mycologic and clinical cure, are frequently omitted from clinical trials. Not surprisingly, clinical trials with stringent efficacy criteria, which assess both mycologic and clinical response/cure without use of subjective methods, appear to have the lowest rates for both therapeutic response and complete cure. Thus, an evaluation of treatment options for onychomycosis cannot solely compare success/failure rates in clinical trials, but requires a critical appraisal of the efficacy criteria utilized in those trials.