Skin self-examination education for early detection of melanoma: a randomized controlled trial of Internet, workbook, and in-person interventions.

BACKGROUND: Early detection of melanoma improves survival. Since many melanoma patients and their spouses seek the care of a physician after discovering their melanoma, an ongoing study will determine the efficacy of teaching at-risk melanoma patients and their skin check partner how to conduct skin self-examinations (SSEs). Internet-based health behavior interventions have proven efficacious in creating behavior change in patients to better prevent, detect, or cope with their health issues. The efficacy of electronic interactive SSE educational intervention provided on a tablet device has not previously been determined. OBJECTIVE: The electronic interactive educational intervention was created to develop a scalable, effective intervention to enhance performance and accuracy of SSE among those at-risk to develop melanoma. The intervention in the office was conducted using one of the following three methods: (1) in-person through a facilitator, (2) with a paper workbook, or (3) with a tablet device used in the clinical office. Differences related to method of delivery were elucidated by having the melanoma patient and their skin check partner provide a self-report of their confidence in performing SSE and take a knowledge-based test immediately after receiving the intervention. METHODS: The three interventions used 9 of the 26 behavioral change techniques defined by Abraham and Michie to promote planning of monthly SSE, encourage performing SSE, and reinforce self-efficacy by praising correct responses to knowledge-based decision making and offering helpful suggestions to improve performance. In creating the electronic interactive SSE educational intervention, the educational content was taken directly from both the scripted in-person presentation delivered with Microsoft PowerPoint by a trained facilitator and the paper workbook training arms of the study. Enrollment totaled 500 pairs (melanoma patient and their SSE partner) with randomization of 165 pairs to the in-person, 165 pairs to the workbook, and 70 pairs to electronic interactive SSE educational intervention. RESULTS: The demographic survey data showed no significant mean differences between groups in age, education, or income. The tablet usability survey given to the first 30 tablet pairs found that, overall, participants found the electronic interactive intervention easy to use and that the video of the doctor-patient-partner dialogue accompanying the dermatologist's examination was particularly helpful in understanding what they were asked to do for the study. The interactive group proved to be just as good as the workbook group in self-confidence of scoring moles, and just as good as both the workbook and the in-person intervention groups in self-confidence of monitoring their moles. While the in-person intervention performed significantly better on a skill-based quiz, the electronic interactive group performed significantly better than the workbook group. The electronic interactive and in-person interventions were more efficient (30 minutes), while the workbook took longer (45 minutes). CONCLUSIONS: This study suggests that an electronic interactive intervention can deliver skills training comparable to other training methods, and the experience can be accommodated during the customary outpatient office visit with the physician. Further testing of the electronic interactive intervention's role in the anxiety of the pair and pair-discovered melanomas upon self-screening will elucidate the impact of these tools on outcomes in at-risk patient populations. TRIAL REGISTRATION: ClinicalTrials.gov NCT01013844; http://clinicaltrials.gov/show/NCT01013844 (Archived by WebCite at http://www.webcitation.org/6LvGGSTKK).

Accuracy of self-report in assessing Fitzpatrick skin phototypes I through VI.

IMPORTANCE: Determining Fitzpatrick skin phototypes (FST) allows physicians to assess a person's risk of developing sunburn and, by extension, the need for sun protection to prevent the development of skin cancer. Reflectance spectrophotometry objectively measures the melanin index and can assist in determining the accuracy of self-report of FST compared with dermatologist-determined FST. OBJECTIVES: To assess whether self-reported or dermatologist-determined FST is more accurate in identifying a participant's FST for FST I through VI and to assess the relevance of the burning and tanning measures for a range of skin types among ethnically diverse participants. DESIGN AND SETTING: A convenience sample of participants in an observational study from June 2, 2010, through December 15, 2010, at an ambulatory academic dermatologic practice and employee health center in an urban city. PARTICIPANTS: Participants, staff, and students of Northwestern University, who self-identified as being non-Hispanic white, Hispanic or Latino, Asian or Pacific Islander, or black. MAIN OUTCOMES AND MEASURES: Melanin index as measured with reflectance spectrophotometry compared with dermatologist- and participant-determined FST. RESULTS: Forty-two percent (114 of 270) of the participants' responses to the burning and tanning questions could not be classified using standard FST definitions. The spectrophotometry measurements for dermatologist-determined FST were significantly different for FST III and IV (P < .001) and FST IV and V (P < .001). The spectrophotometry measurements for participant-determined FST were significantly different for FST III and IV (P < .001) but not for FST IV and V (P = .90). Participant responses to burning and the dermatologist-determined FST were significantly correlated (Spearman ρ, 0.764; P < .001). Participant responses to tanning and the dermatologist-determined FST were not significantly correlated (Spearman ρ, 0.089; P = .15). Spectrophotometry measurements assessing FST were statistically significantly different for FST III through VI (P < .001). CONCLUSIONS AND RELEVANCE: Dermatologist-determined FST is more accurate than self-report for FST III through VI. Rephrasing the questions using specific descriptors that have meaning to people with skin of color, such as skin irritation, tenderness, itching, or skin becoming darker, may allow physicians to more accurately assign a skin phototype and, by inference, assess the risk of these participants developing skin cancer. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01124513.

Sun protection preferences and behaviors among young adult males during maximum ultraviolet radiation exposure activities.

This study explores sun protection attitudes, preferences, and behaviors among young adult males participating in an open-field activity with extreme ultraviolet radiation exposure. Male drum corps members (n = 137) responded to survey questions regarding their behavior and willingness to engage in sun protection and barriers to sunscreen usage. A subset of members (n = 31) participated in cognitive interviews exploring various sunscreen products and intervention techniques. Participants were knowledgeable about health risks and protection benefits regarding sun exposure. Generally, males had positive attitudes and normative beliefs about using sunscreen. A barrier to sunscreen re-application was lack of adequate time to reapply sunscreen during the open field activity. Males preferred a towelette application method, but were unfamiliar with its efficacy and proper use. Thus, they were more likely to use the more familiar sunscreen spray. To increase sun protection behaviors and lower skin cancer risk for males participating in open-field activities, breaks must be allotted every 2 h and have sufficient time to allow sunscreen application. Future development and research into delivery systems that rapidly and evenly apply sunscreen may help lower exposure in this population.

Communication by mothers with breast cancer or melanoma with their children.

Communication of familial risk of breast cancer and melanoma has the potential to educate relatives about their risk, and may also motivate them to engage in prevention and early detection practices. With the Health Insurance Portability and Accountability Act (HIPAA) privacy laws, the patient often becomes the sole communicator of such risks to family members. This study surveys mothers diagnosed with either breast cancer or melanoma and their adult children about their family communication style, knowledge of increased risk, and early detection practices. In both cancer groups, most mothers alerted their children of the risk and need for early detection practices. Breast cancer mothers communicated risk and secondary prevention with early detection by breast self-examination and mammograms whereas the melanoma mothers communicated risk and primary prevention strategies like applying sunscreen and avoiding deliberate tanning. Open communication about health matters significantly increased the likelihood that children engaged in early detection and/or primary prevention behaviors. Examining the information conveyed to at-risk family members, and whether such information motivated them to engage in early detection/prevention behaviors, is key to guiding better cancer prevention communication between doctors and patients.

Melanoma simulation model: promoting opportunistic screening and patient counseling.

IMPORTANCE: Lack of training hampers melanoma recognition by physicians. OBJECTIVE: To evaluate a melanoma simulation model to teach visual assessment and counseling skills. DESIGN AND SETTING: Simulation model study in an academic research setting. PARTICIPANTS: A convenience sample of third-year medical students was randomly assigned to receive the intervention before or after a standardized patient. INTERVENTION: During the primary care clerkship, medical students participated in melanoma skills training using 2 simulation models replicating melanomas and abnormal or benign nevi. Scoring threshold rules for visual assessment and management of pigmented lesions and videos of patient counseling were provided. MAIN OUTCOME MEASURES: Identifying a melanoma moulage and counseling the standardized patient. Secondary measures were preintervention and 2-week postintervention knowledge, attitudes about and confidence in their ability to perform opportunistic surveillance and counseling, as well as identification on the model of clinically suspicious pigmented lesions, lesions needing a biopsy, and lesions to be monitored for change. RESULTS Among 74 students, confidence in their ability to perform opportunistic surveillance improved significantly after skills training (P < .05, χ2 test). Monitoring clinically suspicious lesions for change decreased from 16% (12 of 74) to 3% (2 of 74) and performing a biopsy increased from 80% (59 of 74) to 96% (71 of 74), monitoring benign lesions for change decreased from 43% (32 of 74) to 3% (2 of 74), and biopsying melanoma in situ increased from 10% (7 of 74) to 26% (20 of 74) (P < .05 for all, χ2 test). Detection of the melanoma moulage on the standardized patient occurred more often by trained students (P < .05, χ2 test). CONCLUSION AND RELEVANCE: A 1-hour melanoma simulation education and skills training experience improved performance of opportunistic surveillance, management, and patient counseling by third-year medical students. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01191294.

Mitochondrial reactive oxygen species promote epidermal differentiation and hair follicle development.

Proper regulation of keratinocyte differentiation within the epidermis and follicular epithelium is essential for maintenance of epidermal barrier function and hair growth. The signaling intermediates that regulate the morphological and genetic changes associated with epidermal and follicular differentiation remain poorly understood. We tested the hypothesis that reactive oxygen species (ROS) generated by mitochondria are an important regulator of epidermal differentiation by generating mice with a keratinocyte-specific deficiency in mitochondrial transcription factor A (TFAM), which is required for the transcription of mitochondrial genes encoding electron transport chain subunits. Ablation of TFAM in keratinocytes impaired epidermal differentiation and hair follicle growth and resulted in death 2 weeks after birth. TFAM-deficient keratinocytes failed to generate mitochondria-derived ROS, a deficiency that prevented the transmission of Notch and ß-catenin signals essential for epidermal differentiation and hair follicle development, respectively. In vitro keratinocyte differentiation was inhibited in the presence of antioxidants, and the decreased differentiation marker abundance in TFAM-deficient keratinocytes was partly rescued by application of exogenous hydrogen peroxide. These findings indicate that mitochondria-generated ROS are critical mediators of cellular differentiation and tissue morphogenesis.

Alteration of the EphA2/Ephrin-A signaling axis in psoriatic epidermis.

EphA2 is a receptor tyrosine kinase (RTK) that triggers keratinocyte differentiation upon activation and subsequent downregulation by ephrin-A1 ligand. The objective of this study was to determine whether the EphA2/ephrin-A1 signaling axis was altered in psoriasis, an inflammatory skin condition in which keratinocyte differentiation is abnormal. Microarray analysis of skin biopsies from psoriasis patients revealed increased mRNA transcripts for several members of this RTK family in plaques, including the EphA1, EphA2, and EphA4 subtypes prominently expressed by keratinocytes. Of these, EphA2 showed the greatest upregulation, a finding that was confirmed by quantitative reverse-transcriptase-PCR, immunohistochemistry (IHC), and ELISA. In contrast, psoriatic lesions exhibited reduced ephrin-A ligand immunoreactivity. Exposure of primary keratinocytes induced to differentiate in high calcium or a three-dimensional (3D) raft culture of human epidermis to a combination of growth factors and cytokines elevated in psoriasis increased EphA2 mRNA and protein expression while inducing S100A7 and disrupting differentiation. Pharmacological delivery of a soluble ephrin-A1 peptidomimetic ligand led to a reduction in EphA2 expression and ameliorated proliferation and differentiation in raft cultures exposed to EGF and IL-1α. These findings suggest that ephrin-A1-mediated downregulation of EphA2 supports keratinocyte differentiation in the context of cytokine perturbation.

Nicotinic acetylcholine receptor stimulation impairs epidermal permeability barrier function and recovery and modulates cornified envelope proteins.

AIM: To characterize how nicotinic acetylcholine receptors (nAChRs) influence epidermal barrier function and recovery following prolonged stress or direct nAChR activation or antagonism. MAIN METHODS: Mice were subjected to psychological stress or treated topically with nAChR agonist or antagonist for 3 days. We assessed barrier permeability and recovery by measuring transepidermal water loss (TEWL) before and after barrier disruption. In parallel, we analyzed the production and localization of several epidermal cornified envelope proteins in mouse skin and in human EpiDerm™ organotypic constructs stimulated with a nAChR agonist (nicotine) and/or a nAChR selective antagonist (α-bungarotoxin). KEY FINDINGS: We determined that psychological stress in mice impairs barrier permeability function and recovery, an effect that is reversed by application of the α7 selective nAChR antagonist, α-bungarotoxin (Bung). In the absence of stress, both topical nicotine or Bung treatment alone impaired barrier permeability. We further observed that stress, topical nicotine, or topical Bung treatment in mice influenced the abundance and/or localization of filaggrin, loricrin, and involucrin. Similar alterations in these three major cornified envelope proteins were observed in human EpiDerm™ cultures. SIGNIFICANCE: Perceived psychological stress and nicotine usage can both initiate or exacerbate several dermatoses by altering the cutaneous permeability barrier. Modulation of nAChRs by topical agonists or antagonists may be used to improve epidermal barrier function in skin diseases associated with defects in epidermal barrier permeability.

microRNA-31/factor-inhibiting hypoxia-inducible factor 1 nexus regulates keratinocyte differentiation.

Notch plays a critical role in the transition from proliferation to differentiation in the epidermis and corneal epithelium. Furthermore, aberrant Notch signaling is a feature of diseases like psoriasis, eczema, nonmelanoma skin cancer, and melanoma where differentiation and proliferation are impaired. Whereas much is known about the downstream events following Notch signaling, factors responsible for negatively regulating Notch receptor signaling after ligand activation are incompletely understood. Notch can undergo hydroxylation by factor-inhibiting hypoxia-inducible factor 1 (FIH-1); however, the biological significance of this phenomenon is unclear. Here we show that FIH-1 expression is up-regulated in diseased epidermis and corneal epithelium. Elevating FIH-1 levels in primary human epidermal keratinocytes (HEKs) and human corneal epithelial keratinocytes (HCEKs) impairs differentiation in submerged cultures and in a "three-dimensional" organotypic raft model of human epidermis, in part, via a coordinate decrease in Notch signaling. Knockdown of FIH-1 enhances keratinocyte differentiation. Loss of FIH-1 in vivo increased Notch activity in the limbal epithelium, resulting in a more differentiated phenotype. microRNA-31 (miR-31) is an endogenous negative regulator of FIH-1 expression that results in keratinocyte differentiation, mediated by Notch activation. Ectopically expressing miR-31 in an undifferentiated corneal epithelial cell line promotes differentiation and recapitulates a corneal epithelium in a three-dimensional raft culture model. Our results define a previously unknown mechanism for keratinocyte fate decisions where Notch signaling potential is, in part, controlled through a miR-31/FIH-1 nexus.

Prostaglandin D2 inhibits hair growth and is elevated in bald scalp of men with androgenetic alopecia.

Testosterone is necessary for the development of male pattern baldness, known as androgenetic alopecia (AGA); yet, the mechanisms for decreased hair growth in this disorder are unclear. We show that prostaglandin D(2) synthase (PTGDS) is elevated at the mRNA and protein levels in bald scalp compared to haired scalp of men with AGA. The product of PTGDS enzyme activity, prostaglandin D(2) (PGD(2)), is similarly elevated in bald scalp. During normal follicle cycling in mice, Ptgds and PGD(2) levels increase immediately preceding the regression phase, suggesting an inhibitory effect on hair growth. We show that PGD(2) inhibits hair growth in explanted human hair follicles and when applied topically to mice. Hair growth inhibition requires the PGD(2) receptor G protein (heterotrimeric guanine nucleotide)-coupled receptor 44 (GPR44), but not the PGD(2) receptor 1 (PTGDR). Furthermore, we find that a transgenic mouse, K14-Ptgs2, which targets prostaglandin-endoperoxide synthase 2 expression to the skin, demonstrates elevated levels of PGD(2) in the skin and develops alopecia, follicular miniaturization, and sebaceous gland hyperplasia, which are all hallmarks of human AGA. These results define PGD(2) as an inhibitor of hair growth in AGA and suggest the PGD(2)-GPR44 pathway as a potential target for treatment.

Bald scalp in men with androgenetic alopecia retains hair follicle stem cells but lacks CD200-rich and CD34-positive hair follicle progenitor cells.

Androgenetic alopecia (AGA), also known as common baldness, is characterized by a marked decrease in hair follicle size, which could be related to the loss of hair follicle stem or progenitor cells. To test this hypothesis, we analyzed bald and non-bald scalp from AGA individuals for the presence of hair follicle stem and progenitor cells. Cells expressing cytokeratin15 (KRT15), CD200, CD34, and integrin, α6 (ITGA6) were quantitated via flow cytometry. High levels of KRT15 expression correlated with stem cell properties of small cell size and quiescence. These KRT15(hi) stem cells were maintained in bald scalp samples. However, CD200(hi)ITGA6(hi) and CD34(hi) cell populations--which both possessed a progenitor phenotype, in that they localized closely to the stem cell-rich bulge area but were larger and more proliferative than the KRT15(hi) stem cells--were markedly diminished. In functional assays, analogous CD200(hi)Itga6(hi) cells from murine hair follicles were multipotent and generated new hair follicles in skin reconstitution assays. These findings support the notion that a defect in conversion of hair follicle stem cells to progenitor cells plays a role in the pathogenesis of AGA.