Subcision with and without suction for acne scars: a split-faced, rater-blinded randomized control trial.

Therapeutic options for acne scars include subcision and suction with microdermabrasion, but these treatment modalities have not been studied in conjunction. To compare effectiveness of subcision alone versus subcision with suction for the treatment of facial acne scars. Randomized, split-faced, evaluator-blinded control trial. Participants underwent one subcision treatment on both sides of the face followed by 10 sessions of suction to one side. Photographs at baseline, 1-month, and 4-months were assessed. Primary outcome measures were the validated Acne Scar Severity Scale (ASSS) (0 = no acne scarring, 4 = severe), Acne Scar Improvement Grading Scale (ASIGS) (-100 to 100%), and modified Quantitative Global Scarring Grades (QGSG) (point-based questionnaire instrument), as well as subject preference. Twenty-eight treatment areas and 154 treatments were analyzed. Dermatologist raters found no differences between subcision alone and subcision-suction at 1-month or 4-months. Mean subject-assessed percent improvement for subcision-suction was higher than that for subcision alone at 1-month (37% versus 24%, p = 0.04) but not at 4-months (p = 0.37). Subjects preferred combination therapy to monotherapy at 1-month (50% vs. 21%) and 4-months (43% vs. 21%). While blinded raters did not detect significant differences, subjects perceived combination treatment as working more quickly than monotherapy, and preferred combination treatment at all time points.Clinical trial registration NCT01696513 on Clinicaltrials.gov.

Machine learning identification of patient clusters for cutaneous melanoma.

BACKGROUND: Cutaneous melanoma is a cancer arising in melanocyte skin cells and is the deadliest form of skin cancer worldwide. Although some risk factors are known, accurate prediction of disease progression and probability for metastasis are difficult to ascertain, given the complexity of the disease and the absence of reliable predictive markers. Since early detection and treatment are essential to enhance survival, this study utilizing machine learning (ML) aims to further delineate additional risk factors associated with cutaneous melanoma. METHODS: A Bayesian Gaussian Mixture ML model was created with data from 2056 patients diagnosed with cutaneous melanoma and then used to group the patients into six Clusters based on a Silhouette Score analysis. A t-distributed stochastic neighbor embedding (t-SNE) model was used to visualize the six Clusters. RESULTS: Statistical analysis revealed that Cluster 4 showed a significantly higher rate of metastatic disease, as well as higher Breslow depth at diagnosis, compared to the other five Clusters. Compared to the other five Clusters, patients represented in Cluster 4 also had lower healthcare utilization, fewer dermatology clinic visits, fewer primary care providers, and less frequent colonoscopies and mammograms, and were more likely to smoke and less likely to have a prior diagnosis of basal cell carcinoma. CONCLUSIONS: This study uncovers gaps in healthcare utilization of services among patient groups with cutaneous melanoma as well as possible implications for management of disease progression. Data-driven analyses emphasize the importance of routine clinic visits to dermatologists and/or primary care physicians (PCPs) for early detection and management of cutaneous melanoma. The findings from this study demonstrate that unsupervised ML methodology may serve to define the best candidate patients to benefit from enhanced dermatology/primary care which, in turn, is expected to improve outcomes for cutaneous melanoma.

While ethical considerations predominate, scientific merit can impact Institutional Review Board (IRB) determinations: a cross-sectional study.

BACKGROUND AND OBJECTIVES: To determine the most common reasons for Institutional Review Boards deferral of biomedical research proposals. METHODS: Cross-sectional study administered to chairs, vice-chairs, and co-chairs of IRBs at NIH-funded institutions. RESULTS: Data forms were distributed to IRB chairs at 21 of 25 NIH-funded institutions (four declined to participate), with an institutional response rate of 86% (18/21). Overall, ethical considerations were more likely than scientific merit to be a reason for protocol deferral. Common ethical considerations for deferral were inadequate informed consent, inadequate detail for risk assessment, insufficient protection of participant safety, and inadequate minimization of risks. Important elements of scientific merit were appropriate research design, adequate adverse event reporting, and the importance of knowledge to be gained. Nonsponsored, investigator-initiated proposals (including those receiving internal funding) were more likely to be deferred (66%), usually due to inadequate protocol development (43%), less external vetting and oversight (20%), and submissions from inexperienced faculty (16%). CONCLUSION: Deferrals may be avoided by careful compliance with ethical considerations, and by ensuring sufficient scientific merit of the proposal, with research design optimized for participant safety. Those submitting investigator-initiated proposals may consider obtaining at least partial funding to decrease the risk of deferral.

Relative Prevalence of Contact Allergens in North America in 2018.

BACKGROUND: The American Contact Dermatitis Society Contact Allergen Management Program (CAMP) database was developed to provide patients with safe alternative products free of selected contact allergens. However, the CAMP database also records valuable information including the frequency of contact allergen searches for patients. OBJECTIVES: The aim of the study was to determine the relative prevalence of contact allergens in North America. METHODS: Data from the CAMP database were analyzed from January 1, 2018, to January 1, 2019. The number of searches performed for each specific allergen served as a measure of the relative prevalence for each contact allergen. Results were then stratified by age, sex, atopic history, and patch screening tray used. RESULTS: The 2018 CAMP data show that many of the prevalent allergens are not currently on any contact allergy screening series. These data strongly indicate that testing only to an 80-item screening series will not provide adequate care for many patients with contact allergy. The most prevalent contact allergens seen were fragrance mix, nickel, balsam of Peru, methylchloroisothiazolinone/methylisothiazolinone, and cobalt. Some important differences are seen when stratifying CAMP data by age, sex, atopic history, and patch screening tray used. LIMITATIONS: Possible sources of data error exist because of lack of uniformity of patch test practices. CONCLUSIONS: The CAMP database can be used to determine the relative prevalence of contact allergens, to help develop North American core screening patch test series, and to document the medical necessity of more comprehensive patch testing for patients with recalcitrant contact allergy.

A Comparison of Psoriasis Severity in Pediatric Patients Treated With Methotrexate vs Biologic Agents.

Importance: Few studies have compared the use of methotrexate and biologics, the most commonly used systemic medications for treatment of moderate to severe psoriasis in children. Objective: To assess the real-world, 6-month reduction in psoriasis severity and long-term drug survival (rate and duration of adherence to a specific drug) of methotrexate vs biologics in plaque psoriasis in children. Design, Setting, and Participants: A retrospective medical records review was conducted at 20 European and North American centers. Treatment response was based on site-reported Psoriasis Area and Severity Index (PASI) and/or Physician Global Assessment (PGA) scores at baseline and within the first 6 months of treatment. Participants included all 234 consecutively seen children with moderate to severe psoriasis who received at least 3 months of methotrexate or biologics from December 1, 1990, to September 16, 2014, with sufficient data for analysis. Data analysis was performed from December 14, 2015, to September 1, 2016. Main Outcomes and Measures: PASI, with a range from 0 to 72 (highest score indicating severe psoriasis), and/or PGA, with a scale of 0 (clear), 1 (minimal), 2 (mild), 3 (moderate), 4 (severe), and 5 (very severe). Results: Of 234 pediatric patients (103 boys [44.0%]; 131 girls [56.0%]) treated with methotrexate and/or biologics, 163 patients (69.7%) exclusively received methotrexate, 47 patients (20.1%) exclusively received biologics, and 24 children (10.2%) received methotrexate and biologics sequentially. Of the latter cohort, 23 children were treated initially with methotrexate. Mean (SD) age at initiation was 11.6 (3.7) years for methotrexate and 13.3 (2.9) years for biologics (73.2% for etanercept) (P = .002). Among patients evaluated by a scoring method at 6-month follow-up, 75% or greater improvement in PASI (PASI75) was achieved in 12 of 30 patients (40.0%) receiving methotrexate and 20 of 28 patients (71.4%) receiving biologics, and PGA was clear/almost clear (PGA 0/1) in 41 of 115 patients (35.6%) receiving methotrexate and 18 of 37 patients (48.6%) receiving biologics. Achieving PASI75 and/or PGA 0/1 between baseline and 6 months was more likely with biologics than methotrexate (PASI75: odds ratio [OR], 4.56; 95% CI, 2.02-10.27; P < .001; and PGA 0/1: OR, 2.00; 95% CI, 0.98-4.00; P = .06). Decreased mean PASI and PGA scores were associated with biologics more than with methotrexate (PASI effect, -3.13; 95% CI, -4.33 to -1.94; P < .001; and PGA effect, -0.31; 95% CI, -0.56 to -0.06; P = .02). After 1, 3, and 5 years of use, overall drug survival rates for methotrexate were 77.5%, 50.3%, and 35.9%, and for biologics, the rates were 83.4%, 64.3%, and 57.1%, respectively. Biologics were associated with a better confounder-corrected drug survival than methotrexate (hazard ratio [HR], 2.23; 95% CI, 1.21-4.10; P = .01). Discontinuation owing to lack of response was comparable (HR, 1.64; 95% CI, 0.80-3.36; P = .18). Conclusions and Relevance: Methotrexate and biologics appear to be associated with improvement in pediatric psoriasis, although biologics seem to be associated with greater reduction in psoriasis severity scores and higher drug survival rates than methotrexate in the real-world setting. Additional studies directly comparing these medications should be performed for confirmation.

Risks for noncutaneous second primary malignancy in cutaneous malignant melanoma survivors: an analysis of data from the Surveillance, Epidemiology, and End Results (SEER) program.

BACKGROUND: It is known that malignant melanoma (MM) survivors are at increased risk of future primary MM. However, the risk for noncutaneous second primary malignancies (SPMs) is not as well-understood. METHODS: An observational study utilizing data from the Surveillance, Epidemiology, and End Results (SEER) database was performed, assessing data from patients diagnosed with primary cutaneous MM to measure overall, as well as specific, tumor type and risk of SPM. RESULTS: Of the 132,438 patients recruited in the study population (mean age 55.5 years; 54% male), 23,794 SPMs were observed (O) (18% of patients at a mean age of 68.8 years), while 17,923 SPMs were expected (E) to occur (O : E 1.33, 95% CI 1.31-1.34). Excluding cutaneous MM occurring as a new primary malignancy, there was a significantly increased risk for SPMs among cutaneous MM survivors for each of the following tumor types: eye and orbit melanoma, tracheal, thyroid, salivary gland, retroperitoneum, small intestine, kidney, lymphoid and hematopoietic system, lymphoma overall, non-Hodgkin lymphoma, lymphocytic leukemia overall, chronic lymphocytic leukemia, male genital system (including prostate), and breast. Certain gender-specific trends for SPMs were also detected. CONCLUSIONS: Patients with primary cutaneous MM are at increased risk for primary noncutaneous MM as well as noncutaneous SPMs that include numerous tumor types. Enhanced oncologic surveillance for a variety of tumor types in melanoma survivors is warranted.

A systematic review of the safety and effectiveness of platelet-rich plasma (PRP) for skin aging.

Injection of platelet concentrates for the treatment of aging skin has gained popularity. The objective was to systematically assess the evidence regarding the safety and effectiveness of platelet-rich plasma (PRP) for reducing the visible signs of aging. Cochrane Library, MEDLINE (PubMed), EMBASE, and Scopus were searched from inception to March 2019 for prospective trials and case series assessing PRP for skin aging in 10 or more patients. Twenty-four studies, including 8 randomized controlled trials (RCTs), representing 480 total patients receiving PRP, were included. Based on physician global assessment, injection PRP monotherapy was shown to at least temporarily induce modest improvement in facial skin appearance, texture, and lines. Periorbital fine lines and pigmentation may also benefit. Adjuvant PRP accelerated healing after fractional laser resurfacing. Although the degree of improvement was typically less than 50%, patients generally reported high satisfaction. It was limited by heterogeneity in PRP preparation and administration, and lack of standardization in outcome measures. PRP injections are safe and may be modestly beneficial for aging skin. The evidence is most convincing for improvement of facial skin texture. The persistence of these effects is not known. More high-quality trials with sufficient follow-up are needed to optimize treatment regimens.

Hyperkalemia in women with acne exposed to oral spironolactone: A retrospective study from the RADAR (Research on Adverse Drug Events and Reports) program.

PURPOSE: The necessity of serum potassium monitoring for healthy women who are prescribed spironolactone for acne has been debated. The aim of this study was to compare the incidence of hyperkalemia in women 18 to 45 years of age to that in women 46 to 65 years of age, when treated with oral spironolactone for acne. METHODS AND MATERIALS: Data for all women 18 to 65 years of age who were prescribed oral spironolactone by a dermatologist for acne between January 2006 and October 2016 were extracted for analysis. Retrospective data were included for women who exhibited baseline serum potassium within the normal limits and who had repeat serum potassium monitoring within 12 months after initiation of spironolactone. The rate of incident hyperkalemia was determined. RESULTS: Of 618 women who received spironolactone for acne, 133 had serum potassium monitoring both before and after spironolactone initiation. Nine were excluded due to confounding comorbidities. Of the remaining 124 women, the mean age at initiation of spironolactone was 32 years (range, 18-57 years); 112 women were in the 18 to 45 years age group, and 12 were in the 46 to 65 years age group. All women had serum potassium within normal limits at baseline. Women in the 46 to 65 years age group had a significantly higher rate of incident hyperkalemia after spironolactone initiation compared with women 18 to 45 years of age (2 of 12 women [16.7%] vs. 1 of 112 women [< 1%]; p = .0245). CONCLUSIONS: Although controversy surrounds the clinical utility of serum potassium monitoring in healthy women exposed to spironolactone for acne, based on the findings from this large patient population, monitoring of serum potassium is warranted for women over 45 years of age given an age-related greater risk of hyperkalemia.

Sodium hypochlorite body wash in the management of Staphylococcus aureus-colonized moderate-to-severe atopic dermatitis in infants, children, and adolescents.

OBJECTIVES: A cleansing body wash containing diluted sodium hypochlorite (0.006% NaOCl) was evaluated for management of moderate-to-severe Staphylococcus aureus-colonized, atopic dermatitis in children. METHODS: A 6-week, prospective, open-label study was conducted with 50 evaluable participants (ages 6 months to 17 years) who had moderate-to-severe atopic dermatitis with S aureus skin colonization documented by culture. Participants were instructed to continue using their current medications while using the study product, 0.006% NaOCl body wash, once daily to affected areas for 6 weeks. Primary outcome measures were Investigator's Global Assessment, Eczema Area and Severity Index, and Body Surface Area scores. Secondary outcome measures were the Visual Analog Scale for pruritus, Family Dermatology Life Quality Index, and Patient Satisfaction Questionnaire for Problem Areas. A subject daily diary and a six-item subject questionnaire that provided information on preferences for bleach bath vs body wash were secondary outcome measures. RESULTS: Daily use of the 0.006% NaOCl body wash led to improvement for all outcome measures comparing baseline to 2-week and to 6-week evaluations. Of the 50 skin S aureus-positive subjects, 32/50 (64%) were still positive at 2 weeks. A 36.5% decrease in subject's daily record of topical corticosteroid application at end of study compared to baseline was found. Participant surveys indicated preferences for the body wash over bleach baths. CONCLUSIONS: Sodium hypochlorite (NaOCl) body wash improved all outcome measures for moderate-to-severe S aureus-colonized AD in infants, children, and adolescents. The limited reduction in S aureus further suggests that sodium hypochlorite has ameliorative effects other than antimicrobial actions.

Quantitative evaluation of skin shrinkage associated with non-invasive skin tightening: a simple method for reproducible linear measurement using microtattoos.

Non-invasive skin-tightening devices can induce thermal denaturation and skin shrinkage via externally applied radiofrequency emissions or high-frequency ultrasound. Therefore, the purpose of this study is to develop and test a method for measurement of skin reduction associated with application of such energy devices. Twenty-five healthy participants with mild to moderate skin laxity of the arms were enrolled. Pinpoint microtattoos were placed at each of the treatment sites to delineate two 6 × 12 cm rectangles per subject. A non-stretchable filament, tape and marking pen apparatus was used to measure the size of each rectangle before treatment and at follow-up visit by two blinded investigators. After randomization, one side received a single pass with a radiofrequency device (6.78 MHz), while the contralateral side received multiple passes. Participants underwent two treatment sessions to each side 2 weeks apart, and returned for follow-up 4 weeks after the second treatment. Length and area measurement were analyzed to assess precision and accuracy of measurements and to compare efficacy of treatment between pre- and post-treatment. Concordance correlation coefficients (CCC) demonstrated substantial inter-investigator reliability and precision in length measurements (CCC, 0.94 to 0.98 in pre-treatment; 0.95 to 0.98 in post-treatment). Measurements at the 6-week post-treatment follow-up demonstrated a statistically significant skin reduction in all six of the measured parameters. A simple skin measurement method requiring minimal instrumentation can quantitatively evaluate skin shrinkage associated with non-invasive skin-tightening devices.

Effect of Platelet-Rich Plasma Injection for Rejuvenation of Photoaged Facial Skin: A Randomized Clinical Trial.

Importance: There remains little experimental evidence and no randomized clinical trial to date to confirm the benefit of platelet-rich plasma (PRP) for facial rejuvenation. Objective: To investigate whether PRP injection improves the visual appearance, including texture and color, of photodamaged facial skin. Design, Setting, and Participants: In this randomized clinical trial, participants and raters were masked to groupings. The setting was an academic-based, urban outpatient dermatology practice in Chicago, Illinois. Participants were adults aged 18 to 70 years with bilateral cheek rhytids of Glogau class II or greater. The duration of the study was August 21, 2012, to February 16, 2016. Interventions: Each participant received 3 mL intradermal injections of PRP to one cheek and sterile normal saline to the contralateral cheek. Main Outcomes and Measures: Primary outcomes were photoaging scores (with subscores for fine lines, mottled pigmentation, roughness, and sallowness) as rated by 2 masked dermatologists. Secondary outcomes included participant self-assessment scores of improvement on a 5-point scale (worsening, no change, mild improvement, moderate improvement, or significant improvement), participant overall satisfaction scores on a 4-point scale (not satisfied, slightly satisfied, moderately satisfied, or very satisfied), and participant-reported or investigator-observed adverse events. Results: Of 27 enrolled participants, 19 (mean [SD] age, 46.37 [10.88] years; 17 female) were analyzed. Reported adverse events, which were not associated with the study agent, included redness (n = 18), swelling (n = 16), bruising (n = 14), pruritus (n = 1), skin scaling (n = 1), and dryness of skin (n = 1). No participants reported any adverse events at 12 months. Mean (SD) photoaging scores rated by 2 dermatologists showed no significant difference between PRP and normal saline for fine lines (baseline, 1.00 [0.75] vs 1.05 [0.78]; 2 weeks, 0.95 [0.71] vs 0.95 [0.71]; 3 months, 0.95 [0.71] vs 0.95 [0.71]; 6 months, 0.95 [0.71] vs 0.95 [0.71]), mottled pigmentation (baseline, 1.21 [0.53] vs 1.21 [0.54]; 2 weeks, 1.16 [0.60] vs 1.16 [0.60]; 3 months, 1.00 [0.47] vs 1.11 [0.46]; 6 months, 1.16 [0.69] vs 1.16 [0.69]), skin roughness (baseline, 0.47 [0.61] vs 0.47 [0.61]; 2 weeks, 0.47 [0.61] vs 0.47 [0.61]; 3 months, 0.47 [0.61] vs 0.47 [0.61]; 6 months, 0.37 [0.60] vs 0.37 [0.68]), and skin sallowness (baseline, 1.11 [0.88] vs 1.11 [0.88]; 2 weeks, 0.95 [0.85] vs 0.95 [0.85]; 3 months, 0.58 [0.61] vs 0.58 [0.61]; 6 months, 0.37 [0.68] vs 0.37 [0.68]). At 6 months after a single treatment, participants rated the PRP-treated side as significantly more improved compared with normal saline for texture (mean [SD] self-assessment score, 2.00 [1.20] vs 1.21 [0.54]; P = .02) and wrinkles (mean [SD] self-assessment score, 1.74 [0.99] vs 1.21 [0.54]; P = .03). Conclusions and Relevance: Masked participants noted that both fine and coarse texture improved significantly more with a single treatment of PRP than with normal saline. Both participants and raters found PRP to be nominally but not significantly superior to normal saline. Trial Registration: ClinicalTrials.gov Identifier: NCT01372566.

Effectiveness of Low Doses of Hyaluronidase to Remove Hyaluronic Acid Filler Nodules: A Randomized Clinical Trial.

Importance: Although hyaluronidase is known to remove hyaluronic acid fillers, use of low doses has not been well studied. Objective: To assess the effectiveness and dose-related effect of small quantities of hyaluronidase to treat hyaluronic acid filler nodules. Design, Setting, and Participants: Split-arm, parallel-group, randomized clinical trial at an urban academic center. Participants were 9 healthy women. Recruitment and follow-up occurred from February 2013 to March 2014; data analysis occurred from February to July 2016. Interventions: Each participant received aliquots (buttons) of either of 2 types of hyaluronic acid fillers into bilateral upper inner arms, respectively. At 1, 2, and 3 weeks each button was treated with a constant volume (0.1 mL) of variable-dose hyaluronidase (1.5, 3.0, or 9.0 U per 0.1 mL) or saline control. Main Outcomes and Measures: Both a blinded dermatologist and the participant independently assessed detectability. Results: Seventy-two treatment sites on 9 women (mean [SD] age, 45.8 [15.7] years) received all interventions and were analyzed. There was a significant difference in physician rater assessment between saline and hyaluronidase at 4 weeks (visual detection: mean difference = 1.15; 95% CI, 0.46-1.80; P < .001; palpability: mean difference = 1.22; 95% CI, 0.61-1.83; P < .001) and 4 months (visual detection: mean difference = 0.77; 95% CI, 0.33-1.26; P = .001; palpability: mean difference = 0.82; 95% CI, 0.38-1.25; P < .001) that was mirrored by participant self-assessment at 4 weeks (visual detection: mean difference = 0.87; 95% CI, 0.26-1.48; P = .006; palpability: mean difference = 1.59; 95% CI, 1.41-1.77; P < .001) and 4 months (visual detection: mean difference = 1.31; 95% CI, 1.09-1.53; P < .001; palpability: mean difference = 1.52; 95% CI, 1.03-2.01; P < .001), and hyaluronidase was associated with greater resolution of buttons compared with normal saline. The 9.0-unit hyaluronidase injection sites were significantly less palpable than the 1.5-unit sites at both 4 weeks (mean difference = 0.50; 95% CI, 0.01-.99; P = .045) and 4 months (mean difference = 0.47; 95% CI, 0.14-0.81; P = .007). Dose dependence was more notable for Restylane-L. Conclusions and Relevance: Although very small doses of hyaluronidase can remove hyaluronic acid fillers from patient skin, slightly higher doses often result in more rapid resolution. Trial Registration: clinicaltrials.gov Identifier: NCT01722916.