Analysis of the Nature of IRB Contingencies Required for Informed Consent Document Approval.

The University of Michigan Human Research Protection Program formed a six-member committee to analyze the nature of Institutional Review Board (IRB) staff and board contingencies for the approval of informed consent documents. Of the 100 studies examined, 87% had one or more informed consent contingencies. "Omissions" in documentation (40%) and "better clarity" (24%) accounted for the majority, while "word-smithing" accounted for only 10%. This is one of the first studies to examine the nature of IRB contingencies as they relate to informed consent documents. Educational efforts targeting completeness in documentation and clarity on the part of study teams, and discouraging "word-smithing" on the part of IRBs, could reduce the number of informed consent contingencies and expedite the IRB approval process.

Topical fluorouracil for actinic keratoses and photoaging: a clinical and molecular analysis.

OBJECTIVE: To examine clinical and molecular changes after topical fluorouracil treatment of photodamaged human facial skin for actinic keratoses. DESIGN: Nonrandomized, open-label 2-week treatment with fluorouracil cream, 5%, followed by clinical and molecular evaluation. SETTING: Academic referral center. PATIENTS: Twenty-one healthy volunteers, 56 to 85 years old, with actinic keratoses and photodamage. Interventions Twice-daily application of fluorouracil cream for 2 weeks and biopsies and clinical evaluation at baseline and periodically after treatment. MAIN OUTCOME MEASURES: Gene and protein expression of molecular effectors of epidermal injury, inflammation, and extracellular matrix remodeling 24 hours after fluorouracil treatment; clinical improvement measured by evaluators, photography, and patient questionnaires. RESULTS: One day after the final fluorouracil treatment, gene expression of the effectors of epidermal injury (keratin 16), inflammation (interleukin 1beta), and extracellular matrix degradation (matrix metalloproteinases 1 and 3) was significantly increased. Types I and III procollagen messenger RNA were induced at week 4 (7-fold and 3-fold, respectively). Type I procollagen protein levels were increased 2-fold at week 24. Actinic keratoses and photoaging were statistically significantly improved. Most patients rated photoaging as improved and were willing to undergo the therapy again. CONCLUSIONS: Topical fluorouracil causes epidermal injury, which stimulates wound healing and dermal remodeling resulting in improved appearance. The mechanism of topical fluorouracil in photoaged skin follows a predictable wound healing pattern of events reminiscent of that seen with laser treatment of photoaging.

Improvement of naturally aged skin with vitamin A (retinol).

OBJECTIVE: To evaluate the effectiveness of topical retinol (vitamin A) in improving the clinical signs of naturally aged skin. DESIGN: Randomized, double-blind, vehicle-controlled, left and right arm comparison study. SETTING: Academic referral center. PATIENTS: The study population comprised 36 elderly subjects (mean age, 87 years), residing in 2 senior citizen facilities. INTERVENTION: Topical 0.4% retinol lotion or its vehicle was applied at each visit by study personnel to either the right or the left arm, up to 3 times a week for 24 weeks. MAIN OUTCOME MEASURES: Clinical assessment using a semiquantitative scale (0, none; 9, most severe) and biochemical measurements from skin biopsy specimens obtained from treated areas. RESULTS: After 24 weeks, an intent-to-treat analysis using the last-observation-carried-forward method revealed that there were significant differences between retinol-treated and vehicle-treated skin for changes in fine wrinkling scores (-1.64 [95% CI, -2.06 to -1.22] vs -0.08 [95% CI, -0.17 to 0.01]; P<.001). As measured in a subgroup, retinol treatment significantly increased glycosaminoglycan expression (P = .02 [n = 6]) and procollagen I immunostaining (P = .049 [n = 4]) compared with vehicle. CONCLUSIONS: Topical retinol improves fine wrinkles associated with natural aging. Significant induction of glycosaminoglycan, which is known to retain substantial water, and increased collagen production are most likely responsible for wrinkle effacement. With greater skin matrix synthesis, retinol-treated aged skin is more likely to withstand skin injury and ulcer formation along with improved appearance.

Effect of smoking on aging of photoprotected skin: evidence gathered using a new photonumeric scale.

OBJECTIVES: To develop a reproducible photonumeric scale to assess photoprotected skin aging and to determine whether health and lifestyle factors, such as smoking, affect skin aging in photoprotected sites. DESIGN: Using standard photographs of participants' upper inner arms, we created a 9-point photonumeric scale. Three blinded reviewers used the scale to grade the photographs. Participants answered multiple lifestyle questions. SETTING: Academic outpatient dermatology clinic. PARTICIPANTS: Eighty-two healthy men and women aged 22 to 91 years. Interventions A professional medical photographer took standardized photographs of each participant's upper inner arm. Participants answered standardized health and lifestyle questions. MAIN OUTCOME MEASURES: (1) Interobserver agreement and reproducibility using the photonumeric scale and (2) health and lifestyle factors most predictive of the degree of aging in photoprotected skin. RESULTS: There was good blinded interobserver agreement as measured by the maximum range of disagreement scores for each participant (mean, 0.91; 95% confidence interval, 0.76-1.06). Results were reproducible. We developed a multiple regression model showing that the best model for predicting the degree of aging in photoprotected skin includes 2 variables: age and packs of cigarettes smoked per day. CONCLUSIONS: This photonumeric scale demonstrates good interobserver agreement and good reproducibility. Using this scale, the degree of aging in photoprotected skin was significantly correlated with patient age and a history of cigarette smoking. Additional studies are needed to continue garnering information regarding independent risk factors for aging of photoprotected skin.

Long-term treatment of photoaged human skin with topical retinoic acid improves epidermal cell atypia and thickens the collagen band in papillary dermis.

BACKGROUND: Risk of photocarcinogenesis and the relevance of collagen in wrinkle effacement are two issues related to prolonged use of retinoic acid (RA) that have not been fully addressed. OBJECTIVE: Our purpose was to investigate the degree of epidermal cellular atypia and the thickness of papillary dermal collagen in photoaging after long-term use of RA. METHODS: Thirty-four subjects with photoaged skin were treated daily with 0.05% RA for at least 6 months. Epidermal cellular atypia was graded by means of a semiquantitative scale. Thickness of collagen band was measured by using image-analysis software. RESULTS: Compared with pretreatment findings, melanocytic and keratinocytic atypia was significantly reduced and the collagen band thickness doubled. LIMITATIONS: This was an open-label study. CONCLUSION: Improvement in epidermal cellular atypia is consistent with the ability of RA to act as a chemopreventive agent in epithelial carcinogenesis. Prolonged use also significantly increased collagen matrix deposition in dermal repair zones, which most likely contributes to wrinkle effacement by RA.

Assessment of adapalene gel for the treatment of actinic keratoses and lentigines: a randomized trial.

BACKGROUND: Adapalene is a synthetic retinoid with an established clinical efficacy against acne and good local tolerability. Its effectiveness in the treatment of photodamaged skin has not been studied. OBJECTIVE: We sought to determine the safety and efficacy of adapalene gel in the treatment of actinic keratoses and solar lentigines. METHODS: In a prospective, 2-center, randomized, controlled, investigator-masked, parallel-group study, 90 patients with actinic keratoses and solar lentigines were treated daily with either adapalene gel (0.1% or 0.3%) or its vehicle gel for 4 weeks, followed by twice-daily applications, if tolerated, for up to 9 months. RESULTS: Of the 90 Caucasian patients (69 male, 21 female; mean age 63.1 years) who were enrolled into the study, 83 patients completed 9 months of treatment. With adapalene gel 0.1% and 0.3%, the mean number of actinic keratoses was reduced by 0.5 +/- 0.9 (mean +/- SE) and 2.5 +/- 0.9, respectively. Whereas, with the vehicle gel, there was an increase of 1.5 +/- 1.3 (P <.05). After 1 month of treatment, the patients who received adapalene had significant lightening of solar lentigines as compared with the patients who were treated with vehicle gel (P <.05). After 9 months, 57% and 59% of the patients had lighter lesions in the adapalene 0.1% and 0.3% groups, respectively, in comparison with only 36% in the vehicle group (P <.05). Histologic evaluations revealed improved cellular atypia and reduced epidermal melanin in adapalene-, as compared with vehicle-treated group. The differences, however, were not statistically significant. A retrospective evaluation of paired clinical photographs (before and after 9-month treatment) by 2 dermatologists who were treatment-blinded revealed significant improvement in wrinkles and other clinical features of photoaged skin with adapalene as compared with its vehicle. CONCLUSION: Adapalene gel 0.1% and 0.3% were well tolerated and improved actinic keratoses, solar lentigines, and other features of photodamaged skin.

Thin primary cutaneous melanomas: associated detection patterns, lesion characteristics, and patient characteristics.

BACKGROUND: Public awareness and education may lead to the detection of thinner melanomas, which may result in a decrease in morbidity and mortality rates. Which detection patterns, lesion, and patient characteristics are associated with early detection? METHODS: Using the University of Michigan prospective melanoma database, the detection patterns, lesion characteristics, and patient characteristics of 1515 consecutive patients with in situ or invasive cutaneous melanomas were reviewed. Tumor thickness (measured in millimeters) was evaluated in relationship to detection patterns (patient, physician, spouse), lesion characteristics (change in color, size, shape/elevation, ulceration, bleeding, tenderness, itching), and patient characteristics (gender, skin type, number of atypical and clinically benign nevi, history of sunburn, personal and family history of melanoma). RESULTS: Patient characteristics associated with early detection included female gender, at least one atypical nevus, greater than 20 clinically benign nevi, and/or a personal history of melanoma. Skin types I, II, and III, a history of sunburn, and/or a family history of melanoma were also associated with thinner lesions, but these associations were not statistically significant. Lesion characteristics associated with earlier detection included a change in color, size, shape/elevation, and/or itching. Physician-detected melanomas were significantly thinner than patient or spouse-detected lesions. CONCLUSIONS: Educational campaigns should include increasing melanoma awareness in males and educating the public on the early signs and symptoms. Education should be directed at both high and low-risk groups. Physicians should consider performing total skin examinations routinely on patients. Although they detect a relatively small percentage of all melanomas, physicians detect significantly thinner lesions.