Efficacy and Safety of OnabotulinumtoxinA Treatment of Forehead Lines: A Multicenter, Randomized, Dose-Ranging Controlled Trial.

BACKGROUND: Various onabotulinumtoxinA doses are effective in treating forehead lines (FHL), with a trend toward lower doses. OBJECTIVE: To evaluate efficacy and safety of onabotulinumtoxinA dose-ranging treatment of FHL when the frontalis area and glabellar complex are treated together. MATERIALS AND METHODS: Adults with moderate-to-severe FHL received onabotulinumtoxinA 40 U (FHL, 20 U; glabellar lines [GL], 20 U), 30 U (FHL, 10 U; GL, 20 U), or placebo. Response was assessed at weeks 1, 2, day 30, and monthly to day 180. Coprimary efficacy end points were investigator- and subject-assessed Facial Wrinkle Scale scores of none or mild (day 30). Patient-reported outcomes, onset/duration of effect, and adverse events (AEs) were evaluated. RESULTS: Responder rates (investigator/subject, respectively) were 40-U group, 91.2%/89.5%; 30-U group, 86.4%/81.4%; placebo, 1.7%/5.1%. OnabotulinumtoxinA resulted in significantly greater responder rates than placebo (p < .001). Adverse events were mild to moderate and similar between groups (most common AEs: nasopharyngitis [4.6%] and headache [4.0%]). CONCLUSION: Treatment of FHL with onabotulinumtoxinA 40 and 30 U (in frontalis and glabellar complex muscles) was tolerable, effective, and sustained. Both doses significantly reduced FHL severity; however, the 40-U dose demonstrated a trend toward greater sustained benefit and longer duration of effect versus the 30-U dose, with similar AE rates.

Epidemiologic analysis of change in eyelash characteristics with increasing age in a population of healthy women.

BACKGROUND: Observations that eyelashes become thinner, shorter, and lighter, as women age has not been previously quantified. OBJECTIVE: This study was conducted to investigate associations between eyelash characteristics and age. MATERIALS AND METHODS: The upper natural eyelashes of 179 subjects were photographed and analyzed (digital image analysis); length, thickness, and darkness (intensity: 0 = white and 255 = black) were calculated. Linear regression, including race as a potentially confounding factor, was used to assess the association between age and mean eyelash characteristics. RESULTS: Subjects' mean age was 40.3 (±10.3) years; 46.1% were white, 36.5% Asian, 9.0% Hispanic, 5.1% East Indian, and 3.4% black. Mean eyelash length ranged from 6.39 (±1.02) to 7.98 (±1.15) mm (subjects aged 50-65 years and 22-29 years, respectively). Mean thickness ranged from 1.17 (±0.42) to 1.62 (±0.56) mm (subjects aged 50-65 years and 20-29 years, respectively). Mean intensity ranged from 118.2 (±19.8) to 129.4 (±17.3) (subjects aged 30-39 years and 50-65 years, respectively). Adjusted for race, eyelash length, thickness, and darkness decreased significantly with increasing age (p < .000, p = .0090, and p < .05, respectively). CONCLUSION: Advancing age among an ethnically diverse population of healthy women is associated with significant decreases in eyelash length, thickness, and darkness.

A retrospective review and observational study of outcomes and safety of bimatoprost ophthalmic solution 0.03% for treating eyelash hypotrichosis.

BACKGROUND: The efficacy and safety of bimatoprost ophthalmic solution 0.03% for treating hypotrichosis were shown in a randomized controlled trial and in an open-label study. To date, no data on real-world experience have been published. OBJECTIVE: To evaluate long-term patient satisfaction, usage patterns, and safety of bimatoprost 0.03% in clinical practice. MATERIALS AND METHODS: In this retrospective chart review with a cross-sectional design, adult patients exposed to bimatoprost 0.03% for at least 12 months were randomly sampled from 16 investigational sites. Charts were reviewed for medication usage characteristics and adverse events (AEs). At a study visit, questionnaires eliciting patient-reported outcomes were administered and spontaneously reported AEs were tabulated. RESULTS: Analysis included 585 subjects with a mean (SD) treatment duration of 19.3 (4.3) months. Patient satisfaction with bimatoprost 0.03% was 92.5%; on average, approximately 3 applications per week maintained benefits. Overall, 27.4% of patients spontaneously recalled experiencing AEs while on treatment; however, patient charts showed that only 4 AEs were documented. No instances of iris hyperpigmentation occurred. No serious or severe AEs were noted. CONCLUSION: Treatment with bimatoprost 0.03% for at least 12 months is safe, and long-term use is associated with a high degree of satisfaction.

The South American Glabellar Experience Study (SAGE): a multicenter retrospective analysis of real-world treatment patterns following the introduction of incobotulinumtoxinA in Argentina.

BACKGROUND: IncobotulinumtoxinA was approved in Argentina in 2007 for the treatment of moderate to severe glabellar lines. OBJECTIVE: The authors evaluate real-world changes in facial aesthetic treatment patterns and patient satisfaction following the introduction of incobotulinumtoxinA in Argentina. METHODS: This multicenter, retrospective chart review conducted in Argentina included women who had received at least 2 treatment cycles of onabotulinumtoxinA (Allergan, Irvine, California) for glabellar lines (period 1) prior to switching to incobotulinumtoxinA (Merz Pharma, GmbH, Frankfurt, Germany (period 2). Subjects were given the option to continue with incobotulinumtoxinA treatments (captured in period 2) or switch back to onabotulinumtoxinA (documented as period 3). Medical records were reviewed for demographics, dosing, reason for switching between products, treatment satisfaction, and interval between injection cycles. RESULTS: One hundred ten women were enrolled and collectively received 662 treatment cycles with botulinum toxin. Subjects were switched to incobotulinumtoxinA at unit doses that were numerically and statistically similar to the onabotulinumtoxinA doses they received in period 1. Most subjects (92%) initially switched to incobotulinumtoxinA because of lower cost. Ninety-two subjects (84%) switched back to onabotulinumtoxinA in period 3, most commonly due to insufficient duration of effect with incobotulinumtoxinA (61/92; 66%). Subjects reported satisfaction with treatment in >90% of their onabotulinumtoxinA visits and in 34% of their incobotulinumtoxinA visits. Median interinjection intervals with onabotulinumtoxinA were 180.3 days (period 1) and 176.9 days (period 3) and 144.3 days with incobotulinumtoxinA in period 2. CONCLUSIONS: In this real-world setting, subjects did not appear to perceive the same facial aesthetic benefits from incobotulinumtoxinA as onabotulinumtoxinA when the products were administered at comparable doses.

OnabotulinumtoxinA: a meta-analysis of duration of effect in the treatment of glabellar lines.

BACKGROUND: Duration of effect of aesthetic treatments with botulinum toxin potentially influences subject satisfaction, treatment frequency, and annual costs, but quantitative outcomes for measuring duration of effect and correlations with subject satisfaction have yet to be fully elucidated. METHODS AND MATERIALS: Phase III clinical trials with similar designs were identified and their data pooled to ascertain duration of clinical effect of onabotulinumtoxinA in glabellar muscles. Duration was calculated using the Kaplan-Meier method for investigator-rated Facial Wrinkle scale (FWS) scores and subject global assessment (SGA) of glabellar lines. Responders were determined according to FWS score at maximum contraction and at repose 30 days after injection. RESULTS: Data from four trials with 621 onabotulinumtoxinA-treated (20 U) subjects were analyzed, 523 of these (84.2%) were identified as day-30 responders on the FWS at maximum contraction. Pooled median duration of effect for day-30 responders was 120 days for FWS at maximum contraction and 131 days for FWS at repose. Higher day 30 SGA scores were correlated with a greater duration of effect on dynamic, but not static lines. CONCLUSION: Treatment of glabellar lines with 20 U of onabotulinumtoxinA resulted in sustained clinical benefit for 4 months in more than 50% of responders; subject satisfaction increased with duration of effect.

Skeletal muscle contractions uncoupled from gravitational loading directly increase cortical bone blood flow rates in vivo.

The direct and indirect effects of muscle contraction on bone microcirculation and fluid flow are neither well documented nor explained. However, skeletal muscle contractions may affect the acquisition and maintenance of bone via stimulation of bone circulatory and interstitial fluid flow parameters. The purposes of this study were to assess the effects of transcutaneous electrical neuromuscular stimulation (TENS)-induced muscle contractions on cortical bone blood flow and bone mineral content, and to demonstrate that alterations in blood flow could occur independently of mechanical loading and systemic circulatory mechanisms. Bone chamber implants were used in a rabbit model to observe real-time blood flow rates and TENS-induced muscle contractions. Video recording of fluorescent microspheres injected into the blood circulation was used to calculate changes in cortical blood flow rates. TENS-induced repetitive muscle contractions uncoupled from mechanical loading instantaneously increased cortical microcirculatory flow, directly increased bone blood flow rates by 130%, and significantly increased bone mineral content over 7 weeks. Heart rates and blood pressure did not significantly increase due to TENS treatment. Our findings suggest that muscle contraction therapies have potential clinical applications for improving blood flow to cortical bone in the appendicular skeleton.

Mucosal regeneration of a duodenal defect using small intestine submucosa.

Intestinal tissue engineering has the potential of developing new treatment strategies for patients with a deficit in intestinal surface area. The purpose of this study was to investigate the capacity of small intestine submucosa (SIS) to regenerate intestinal epithelia in a rodent model for a duodenal defect. A duodenotomy was created in 20 Sprague-Dawley rats and was repaired with a circular patch of SIS. The repaired sites were retrieved 1, 2, 4, and 12 weeks after implantation. The size of the residual mucosal defect was measured. The retrieved tissues were fixed in formalin and processed by standard histologic techniques. The animals tolerated the procedure well. The mean size of the mucosal defects significantly decreased with time. Complete epithelialization of the defects was noted within 4 weeks in three of five samples. Histologically, the defects were lined with crypts and villi, but the muscularis layer did not regenerate. In the rodent model, SIS can be used as a patch to repair a duodenotomy. Mucosal regeneration was observed in the area of the defect. Further studies will determine whether SIS may be used to preserve or increase mucosal surface area in patients whose bowel length is compromised.