Working Together to Address Women's Health in Research and Drug Development: Summary of the 2017 Women's Health Congress Preconference Symposium.

Historically, women have been underrepresented in clinical research, requiring physicians to extrapolate medical recommendations for women from clinical research done in cohorts consisting predominantly of male participants. While government-funded clinical research has achieved gender parity in phase-3 clinical trials across many biomedical disciplines, improvements are still needed in several facets of women's health research, such as the inclusion of women in early-phase clinical trials, the inclusion of pregnant women and women with physical and intellectual disabilities, the consideration of sex as a biological variable in preclinical research, and the analysis and reporting of sex and gender differences across the full biomedical research continuum. The National Institutes of Health (NIH) Office of Research on Women's Health and the Office of Women's Health of the U.S. Food and Drug Administration (FDA) cosponsored a preconference symposium at the 25th Annual Women's Health Congress, held in Arlington, VA in April, 2017, to highlight gains made and remaining needs regarding the representation of women in clinical research, to introduce innovative procedures and technologies, and to outline revised policy for future studies. Six speakers presented information on a range of subjects related to the representation of women in clinical research and federal initiatives to advance precision medicine. Topics included the following: the return on investment from the NIH-funded Women's Health Initiative; progress in including women in clinical trials for FDA-approved drugs and products; the importance of clinical trials in pregnant women; FDA initiatives to report drug safety during pregnancy; the NIH-funded All of Us Research Program; and efforts to enhance FDA transparency and communications, including the introduction of Drug Trials Snapshots. This article summarizes the major points of the presentations and the discussions that followed.

Prospective Controlled Trial for the Treatment of Acne Keloidalis Nuchae With a Long-Pulsed Neodymium-Doped Yttrium-Aluminum-Garnet Laser.

BACKGROUND: Acne keloidalis nuchae (AKN) is a chronic scarring folliculitis with limited interventions of both high efficacy and low morbidity. OBJECTIVE: To assess the efficacy of the long-pulsed 1064-nm neodymium-doped yttrium-aluminum-garnet (Nd:YAG) laser and topical steroids as a treatment for AKN compared to topical steroids alone. METHODS: We conducted a single-blinded, randomised, within-patient right-left controlled trial (n = 13). Eight monthly laser treatments were performed on the treated half of the scalp, and triamcinolone 0.1% cream was applied to both sides twice daily. Treatment response was measured using a global assessment score (0 to 10). RESULTS: The laser-treated side showed greater improvement in global assessment score. The mean change was -3.2 (-49.2%) on the treated side and -2.2 (-32.8%) on the control side ( P = .144). Papules responded well to laser treatment, while larger plaques and nodules showed limited improvement. In the 10 patients with papules only, the difference in improvement between the treated and control sides was statistically significant (mean change was -3.5 [-59.3%] for the treated side and -1.8 [-29.5%] for the control side, P = .031). LIMITATIONS: This study was limited by a small sample size and a high dropout rate, as well as the lack of a standardised scoring system for AKN. CONCLUSION: The long-pulsed Nd:YAG laser in conjunction with topical steroids shows promising results in the treatment of AKN, particularly the papular component, and is well tolerated by patients.

Long-term follow-up of patients undergoing autologous noncultured melanocyte-keratinocyte transplantation for vitiligo and other leukodermas.

BACKGROUND: Persistence of pigmentation after a melanocyte-keratinocyte transplantation procedure (MKTP) is an important consideration for efficacy. OBJECTIVE: We sought to determine long-term repigmentation of MKTP in vitiligo and other leukodermas. METHODS: A retrospective review of electronic medical records was conducted for all MKTPs performed at Henry Ford Hospital between January 2009 and April 2014. Repigmentation was assessed by a 5-point grading scale (poor to excellent) and Vitiligo Area Scoring Index (VASI). RESULTS: One hundred patients had MKTP performed at 236 anatomically-based lesions (ABLs); 63 patients with 157 ABLs had long-term data available (12-72 months; median, 24 months). Segmental vitiligo, nonsegmental vitiligo, and physical leukoderma demonstrated improvement in VASI scores: -75.6 ± 24.6%, -59.2 ± 36.6%, and -32.4 ± 33.5%, respectively. In vitiligo, at 24, 48, and 72 months after MKTP, 53%, 64%, and 53% of ABLs, respectively, maintained >75% repigmentation. Skin phototype, age, and anatomic location of ABLs had no significant effect on the outcome of treatment. LIMITATIONS: Limitations of the study include the retrospective design with uncontrolled, postoperative adjuvant treatments and inconsistent compliance to scheduled follow-up evaluations. CONCLUSIONS: MKTP provides satisfactory long-term repigmentation in the majority of appropriately selected patients with leukoderma. MKTP can maintain repigmentation for at least 72 months.

The Food and Drug Administration Office of Women's Health: Impact of Science on Regulatory Policy: An Update.

The U.S. Food and Drug Administration Office of Women's Health (FDA OWH) has supported women's health research for ∼20 years, funding more than 300 studies on women's health issues, including research on diseases/conditions that disproportionately affect women in addition to the evaluation of sex differences in the performance of and response to medical products. These important women's health issues are studied from a regulatory perspective, with a focus on improving and optimizing medical product development and the evaluation of product safety and efficacy in women. These findings have influenced industry direction, labeling, product discontinuation, safety notices, and clinical practice. In addition, OWH-funded research has addressed gaps in the knowledge about diseases and medical conditions that impact women across the life span such as cardiovascular disease, pregnancy, menopause, osteoporosis, and the safe use of numerous medical products.

Guidelines for phototherapy of mycosis fungoides and Sézary syndrome: A consensus statement of the United States Cutaneous Lymphoma Consortium.

BACKGROUND: Ultraviolet light (UVL) is a long established treatment for mycosis fungoides (MF) and Sézary syndrome (SS), subtypes of cutaneous T-cell lymphoma (CTCL). Treatments have traditionally included broadband, narrowband ultraviolet B light (UVB) and psoralen plus ultraviolet A light photochemotherapy (PUVA), but more recently, treatment options have expanded to include UVA1 and excimer laser. UVL is used either as monotherapy or as an adjuvant to systemic therapy, demonstrating efficacy in many cases that equal or surpass systemic medications. Despite its utility and duration of use, the current practice of using UVL guidelines for psoriasis to treat patients with MF/SS is problematic because the goals of prolonging survival and preventing disease progression are unique to CTCL compared to psoriasis. OBJECTIVES: We sought to develop separate guidelines for phototherapy for MF/SS for both clinical practice and for clinical trials. METHODS: Literature review and cutaneous lymphoma expert consensus group recommendations. RESULTS: This paper reviews the published literature for UVB and UVA/PUVA in MF/SS and suggests practical standardized guidelines for their use. LIMITATIONS: New standardization of phototherapy. CONCLUSIONS: These guidelines should allow the comparison of results with phototherapy in MF/SS across different stages of patients, centers, and in combination with other agents in practice and in clinical trials.

Afamelanotide and narrowband UV-B phototherapy for the treatment of vitiligo: a randomized multicenter trial.

IMPORTANCE: Narrowband UV-B (NB-UV-B) phototherapy is used extensively to treat vitiligo. Afamelanotide, an analogue of α-melanocyte-stimulating hormone, is known to induce tanning of the skin. OBJECTIVE: To evaluate the efficacy and safety of combination therapy for generalized vitiligo consisting of afamelanotide implant and NB-UV-B phototherapy. DESIGN, SETTING, AND PARTICIPANTS: This study was performed in 2 academic outpatient dermatology centers and 1 private dermatology practice. We enrolled men and women 18 years or older with Fitzpatrick skin phototypes (SPTs) III to VI and a confirmed diagnosis of nonsegmental vitiligo that involved 15% to 50% of total body surface area. Vitiligo was stable or slowly progressive for 3 months. Patients were randomized to combination therapy (n = 28) vs NB-UV-B monotherapy (n = 27). After 1 month of NB-UV-B phototherapy, 16 mg of afamelanotide was administered subcutaneously to the combination therapy group monthly for 4 months while NB-UV-B phototherapy continued; the other group continued to receive NB-UV-B monotherapy. INTERVENTIONS: Narrowband UV-B monotherapy vs combined NB-UV-B phototherapy and afamelanotide. MAIN OUTCOMES AND MEASURES: Response on the Vitiligo Area Scoring Index and Vitiligo European Task Force scoring system. RESULTS: Response in the combination therapy group was superior to that in the NB-UV-B monotherapy group (P < .05) at day 56. For the face and upper extremities, a significantly higher percentage of patients in the combination therapy group achieved repigmentation, and at earlier times (face, 41.0 vs 61.0 days [P = .001]; upper extremities, 46.0 vs 69.0 days [P = .003]). In the combination therapy group, repigmentation was 48.64% (95% CI, 39.49%-57.80%) at day 168 vs 33.26% (95% CI, 24.18%-42.33%) in the NB-UV-B monotherapy group. Notable adverse events included erythema in both groups and minor infections and nausea in the combination therapy group. Comparison between Fitzpatrick SPTs showed patients with SPTs IV to VI in the combination therapy group had improvement in the Vitiligo Area Scoring Index at days 56 and 84 (P < .05); no significant difference was noted in patients with SPT III. CONCLUSIONS AND RELEVANCE: A combination of afamelanotide implant and NB-UV-B phototherapy resulted in clinically apparent, statistically significant superior and faster repigmentation compared with NB-UV-B monotherapy. The response was more noticeable in patients with SPTs IV to VI. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01430195.

Comparison of photodermatoses in African-Americans and Caucasians: a follow-up study.

BACKGROUND/PURPOSE: Only a few studies have compared frequencies of photodermatoses among different races and skin types. This is an extension of a study performed by Kerr and Lim and evaluates the frequency of photodermatoses in African-Americans compared with Caucasians in the same institution during an 8-year period. METHODS: Retrospective chart review was performed, including dermatology clinic charts from October 2004 to August 2012 with International Classification of Diseases, Ninth Revision diagnostic codes related to photodermatoses. RESULTS: We identified 229 patients with photodermatoses. Of these, 138 (46.6%) were African-American and 63 (42.2%) were Caucasian. Statistically significant differences in the distribution of photodermatoses in African-Americans and Caucasians, respectively, were as follows: phototoxic drug eruption (0.7% and 15.9%, P < 0.0001), phytophotodermatitis (0% and 6.3%, P = 0.009), polymorphous light eruption (PMLE) (86.2% and 54%, P < 0.0001) and porphyrias (0% and 7.9%, P = 0.003). CONCLUSION: Combined with data from Kerr and Lim, this is the largest study of photodermatoses in African-Americans to date. Congruent to former studies, photodermatoses do occur regularly in dark-skinned individuals. Overall, the frequency of photodermatoses in African-Americans and Caucasians are similar; however, PMLE occurs more commonly in African-Americans, and porphyias and phototoxicity occur more commonly in Caucasians.

Quantitative skin color measurements in acanthosis nigricans patients: colorimetry and diffuse reflectance spectroscopy.

Tristimulus colorimetry and diffuse reflectance spectroscopy (DRS) are white-light skin reflectance techniques used to measure the intensity of skin pigmentation. The tristimulus colorimeter is an instrument that measures a perceived color and the DRS instrument measures biological chromophores of the skin, including oxy- and deoxyhemoglobin, melanin and scattering. Data gathered from these tools can be used to understand morphological changes induced in skin chromophores due to conditions of the skin or their treatments. The purpose of this study was to evaluate the use of these two instruments in color measurements of acanthosis nigricans (AN) lesions. Eight patients with hyperinsulinemia and clinically diagnosable AN were seen monthly. Skin pigmentation was measured at three sites: the inner forearm, the medial aspect of the posterior neck, and anterior neck unaffected by AN. Of the three, measured tristimulus L*a*b* color parameters, the luminosity parameter L* was found to most reliably distinguish lesion from normally pigmented skin. The DRS instrument was able to characterize a lesion on the basis of the calculated melanin concentration, though melanin is a weak indicator of skin change and not a reliable measure to be used independently. Calculated oxyhemoglobin and deoxyhemoglobin concentrations were not found to be reliable indicators of AN. Tristimulus colorimetry may provide reliable methods for respectively quantifying and characterizing the objective color change in AN, while DRS may be useful in characterizing changes in skin melanin content associated with this skin condition.

Skin-of-color epidemiology: a report of the most common skin conditions by race.

To quantify and compare diagnoses according to race in pediatric Health Maintenance Organization (HMO) health plan patients seen in a general dermatology clinic over a 10-year period. Retrospective cohort of health plan pediatric patients seen in the dermatology clinic between 1997 and 2007 was established using an electronic medical record database. Diagnoses and diagnostic codes were recorded according to International Classification of Diseases, Ninth Revision (ICD-9) diagnostic codes grouped on their first three digits. The proportion of patients with each diagnosis was determined according to race and sex, and the 10 most common diagnoses were determined. The most common diagnoses observed in all pediatric patients were acne (28.6%), dermatitis (19.4%), and warts (16.2%), accounting for more than 60% of dermatologic visits by children. Although acne (29.9%), warts (22.6%), and dermatitis (13.1%) were also the most common diagnoses for Caucasian children, African American pediatric patients were most commonly seen for dermatitis (29.0%), acne (27.5%), and dermatophytosis (10.2%). The three most common diagnoses for Asian patients were dermatitis (29.1%), acne (22.2%), and warts (12.6%). Acne remains one of the most common dermatologic diagnoses in children of all races. Differences in frequency of office visits for dermatitis, warts, and dermatophytosis were seen when comparing children of other races with Caucasian children.

Systemic analyses of immunophenotypes of peripheral T cells in non-segmental vitiligo: implication of defective natural killer T cells.

Although it is widely believed that non-segmental vitiligo (NSV) results from the autoimmune destruction of melanocytes, a clear understanding of defects in immune tolerance, which mediate this uncontrolled self-reactivity, is still lacking. In the present study, we systemically evaluated circulating regulatory T (Treg) cells, including CD4(+) CD25(+) FoxP3(+) Treg cells and invariant natural killer T (iNKT) cells, as well as naïve and memory CD4(+) and CD8(+) T cells and their cytokine production, in a cohort of 43 progressive NSV patients with race-, gender-, and age-matched healthy controls. We found that the general immunophenotypes of CD4(+) and CD8(+) T cells and the percentage of CD4(+) CD25(+) FoxP3(+) Tregs were comparable between NSV and healthy controls. However, percentages of peripheral iNKT cells were significantly decreased in NSV patients compared to that in healthy controls. Our data confirm the previous notion that the percentage of peripheral CD4(+) CD25(+) FoxP3(+) Tregs remains unaltered in NSV and suggests the involvement of defective iNKT cells in the pathogenesis of NSV.

Melanocyte-keratinocyte transplantation procedure in the treatment of vitiligo: the experience of an academic medical center in the United States.

BACKGROUND: Vitiligo is a disfiguring disease with limited treatment options. Surgical treatment is underused in the United States because of perceived risk of infection, costs, and difficulty of the procedure. OBJECTIVE: We sought to determine the efficacy and safety of the melanocyte-keratinocyte transplantation procedure (MKTP) in an academic dermatology department in the United States. METHODS: This prospective, uncontrolled, open-label study enrolled patients aged 18 years or older with a self-reported history of vitiligo and no new or expanding lesions for at least 6 months before surgery. Patients with a history of koebnerization or keloid formation were excluded. Patients underwent autologous MKTP. Repigmentation during a 3- to 6-month follow-up period was assessed categorically and by modified Vitiligo Area Scoring Index. Safety was assessed by frequency of adverse events. RESULTS: Of the 28 patients who underwent 36 procedures, 23 patients who underwent 29 procedures completed the 3- to 6-month follow-up period. Data for these 29 procedures show excellent repigmentation (ie, 95%-100%) after the MKTP in 17%, and good repigmentation (ie, 65%-94%) in 31%. Fair (64%-25%) and poor (24%-0%) repigmentation were achieved in 10% and 41% of patients, respectively. Average percent change in Vitiligo Area Scoring Index was -45% (95% confidence interval -64% to -26%), signifying an improvement in pigmentation. LIMITATIONS: Limitations include small sample size and lack of a control group. CONCLUSIONS: The MKTP is an effective and well-tolerated procedure based upon categorical and Vitiligo Area Scoring Index assessments of repigmentation.

Critical comparison of diffuse reflectance spectroscopy and colorimetry as dermatological diagnostic tools for acanthosis nigricans: a chemometric approach.

Quantification of skin changes due to acanthosis nigricans (AN), a disorder common among insulin-resistant diabetic and obese individuals, was investigated using two optical techniques: diffuse reflectance spectroscopy (DRS) and colorimetry. Measurements were obtained from AN lesions on the neck and two control sites of eight AN patients. A principal component/discriminant function analysis successfully differentiated between AN lesion and normal skin with 87.7% sensitivity and 94.8% specificity in DRS measurements and 97.2% sensitivity and 96.4% specificity in colorimetry measurements.