Evaluating clinical trial design: systematic review of randomized vehicle-controlled trials for determining efficacy of benzoyl peroxide topical therapy for acne.

Determined efficacies of benzoyl peroxide may be affected by study design, implementation, and vehicle effects. We sought to elucidate areas that may allow improvement in determining accurate treatment efficacies by determining rates of active treatment and vehicle responders in randomized controlled trials assessing the efficacy of topical benzoyl peroxide to treat acne. We conducted a systematic review of randomized vehicle-controlled trials evaluating the efficacy of topical benzoyl peroxide for the treatment of acne. We compared response rates of vehicle treatment arms versus those in benzoyl peroxide arms. Twelve trials met inclusion criteria with 2818 patients receiving benzoyl peroxide monotherapy treatment and 2004 receiving vehicle treatment. The average percent reduction in total number of acne lesions was 44.3 (SD = 9.2) and 27.8 (SD = 21.0) for the active and vehicle treatment groups, respectively. The average reduction in non-inflammatory lesions was 41.5 % (SD = 9.4) in the active treatment group and 27.0 % (SD = 20.9) in the vehicle group. The average percent decrease in inflammatory lesions was 52.1 (SD = 10.4) in the benzoyl peroxide group and 34.7 (SD = 22.7) in the vehicle group. The average percentage of participants achieving success per designated study outcomes was 28.6 (SD = 17.3) and 15.2 (SD = 9.5) in the active treatment and vehicle groups, respectively. Patient responses in randomized controlled trials evaluating topical acne therapies may be affected by clinical trial design, implementation, the biologic effects of vehicles, and natural disease progression. "No treatment" groups may facilitate determination of accurate treatment efficacies.

US-National Institutes of Health-funded research for cutaneous wounds in 2012.

Chronic cutaneous wounds are a major burden on patients, healthcare providers, and the US healthcare system. This study, carried out in part by the Wound Healing Society's Government Regulatory Committee, aimed to evaluate the current state of National Institutes of Health funding of cutaneous wound healing-related research projects. National Institutes of Health Research Portfolio Online Reporting Tools Expenditures & Results system was used to identify wound healing projects funded by the National Institutes of Health in the 2012 fiscal year. Research projects focusing on cutaneous wound prevention/education, mechanisms, complications, treatment, or imaging/monitoring were included in the analysis. Ninety-one projects were identified, totaling a collective funding of $29,798,991 and median funding of $308,941. Thirteen institutes/centers from the National Institutes of Health were responsible for awarding funds; three of which (National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institute of General Medical Sciences, National Institute of Diabetes and Digestive and Kidney Diseases) accounted for 60.4% of the grant funding. The predominant funding mechanisms included R01 (48.3%), R43 (14.3%), and R21 (9.9%). New applications and pre-existing applications accounted for 39.6 and 55.0% of the awarded grants, respectively. Grants awarded to investigators affiliated with universities accounted for 68.1% of grants and 25.3% were to investigators in the private sector. This analysis of current National Institutes of Health funding may facilitate more transparency of National Institutes of Health-allocated research funds and serve as an impetus to procure additional support for the field of wound healing.

Postinflammatory hyperpigmentation secondary to external insult: an overview of the quantitative analysis of pigmentation.

CONTEXT: Despite new technologies, few studies have quantified changes in melanocyte numbers associated with postinflammatory hyperpigmentation (PIH) secondary to exogenous causes. OBJECTIVE: This article aims to review what is known about the pathogenesis of PIH secondary to external insults and its relationship to the resultant degree of quantitative changes in melanocytes. METHODS: We performed a review of articles exploring PIH resulting from external cutaneous insults retrieved through database searching. We reviewed relevant articles for the pathogenesis, histopathology, and quantitative changes in melanocytes related to specific etiologies of PIH. Methodologies to quantify pigmentation changes in dermatologic conditions with clinical hyperpigmentation were also explored. RESULTS: Significant increases in melanocyte counts of irritant affected skin is seen compared with melanocyte counts of unaffected skin. An increase in melanocyte counts was also found for spontaneous inflammatory dermatoses, even in the absence of clinical hyperpigmentation. Furthermore, changes in melanocyte density and appearance are also seen secondary to inflammation. In addition, increases in epidermal melanocytes are seen with cutaneous exposure to certain agents, and melanocyte increases vary by exposure agent. CONCLUSIONS: The degree of hyperpigmentation related to the intensity and duration of exposure to the causative factors of PIH is essential to better understand the pathophysiology of the disease process. The application of new methodologies to determine quantitative changes in melanocytes elicited by specific causative inflammatory agents has implications to prevent PIH, add to knowledge about disease duration, to develop better treatments for PIH, and to aid our understanding of the biology of the melanocyte.

Benzene absorption in animals and man: an overview.

Benzene is a widespread, naturally occurring substance of environmental concern as systemic exposure in humans is proven to be carcinogenic. Dermal exposure is a common and significant route of systemic entry and percutaneous absorption is critical in exposure risk assessment. This article reviews the scientific principles, methodologies, and research behind the multiple steps of the percutaneous absorption of benzene in animals and man and the application of this information to optimize exposure risk assessments. A focus on occupational exposures to benzene is made with an exploration of the limitations of current preventative measures and hazard assessments. Finally, recommendations for future research to fill existing knowledge gaps are made.

Randomized, vehicle-controlled trials of topical 5-fluorouracil therapy for actinic keratosis treatment: an overview.

Actinic keratoses are common in older individuals and topical immunotherapy is an important treatment when multiple lesions are present. To assess the efficacy of 5-fluorouracil in treating actinic keratoses, a systematic review of randomized, vehicle-controlled trials was performed. Percentages of 5-fluorouracil and vehicle responders were determined by absolute clearance and mean percent reduction in lesion count. Four trials with 399 and 269 participants in active treatment and vehicle groups, respectively, were evaluated. After 4 weeks of treatment, total clearance and mean lesion count reduction were 52.6 and 90.2% in the treatment group versus 0.85 and 28.3% in the vehicle group, respectively. Topical 5-fluorouracil is efficacious in treating actinic keratoses; however, vehicle responses warrant further investigation of study design and disease severity scales.

Placebo response in relation to clinical trial design: a systematic review and meta-analysis of randomized controlled trials for determining biologic efficacy in psoriasis treatment.

There is a need to better define how the efficacy of investigational drugs is affected by study design, implementation, and placebo responses in randomized controlled trials. The improvements observed in placebo groups within trials examining psoriasis treatments may be partially due to study design and implementation. We conducted a systematic review of randomized placebo-controlled trials assessing the efficacy of biologics in the treatment of psoriasis and psoriatic arthritis to evaluate rates of placebo and active drug responders to determine specific factors within study design that may contribute to placebo responses. We included randomized, placebo-controlled trials of etanercept, infliximab, adalimumab, golimumab, ustekinumab, alefacept, and efalizumab that utilized Psoriasis Area Severity Index as an outcomes measure. We compared the rates of the placebo treatment arm versus the active drug arm achieving 75 % improvement of Psoriasis Area Severity Index. 31 trials involving 8285 active treatment and 3999 placebo patients were included. Rates of placebo responders (4.14 %) were significantly lower than active drug responders (48.4 %). The overall odds ratio calculated was 23.94 (p < 0.0001, 95 % CI 16.02-35.76). Binomial regression models showed that treatment indication, randomization fraction, a PASI inclusion requirement, and the time period of outcomes measure documentation affect placebo responses. Placebo responses seen in randomized controlled trials evaluating biologics in the treatment of psoriasis are not likely due to a physiologic mechanism, but may be secondary to chronic disease course and factors of clinical trial design and implementation.

Application of mobile teledermatology for skin cancer screening.

BACKGROUND: With advancements in mobile technology, cellular phone-based store-and-forward teledermatology may be applied to skin cancer screening. OBJECTIVE: We sought to determine diagnostic and management concordance between in-person and teledermatology evaluations for patients at skin cancer screening whose clinical images and history were transmitted through mobile phones. METHODS: A total of 86 patients with 137 skin lesions presented to a skin cancer screening event in California. These patients' clinical history and skin images were captured by a software-enabled mobile phone. Patients were assessed separately by an in-person dermatologist and a teledermatologist, who evaluated the mobile phone-transmitted history and images. Diagnostic and management concordance was determined between the in-person and teledermatology evaluations. RESULTS: The primary categorical diagnostic concordance was 82% between the in-person dermatologist and the teledermatologist (95% confidence interval 0.73-0.89), with a Kappa coefficient of 0.62 indicating good agreement. The aggregated diagnostic concordance between the in-person dermatologist and the teledermatologist was 62% (95% confidence interval 0.51-0.71), with Kappa coefficient of 0.60 indicating good agreement. Management concordance between the in-person dermatologist and the teledermatologist was 81% (95% confidence interval 0.72-0.88), with a Kappa coefficient of 0.57, which indicates moderate agreement between the dermatologists. Multivariate analysis showed that older age and presentation of atypical nevus were significantly associated with disagreement in diagnosis between the teledermatologist and in-person dermatologist, after adjusting for other factors. LIMITATIONS: Dermatoscopic images were not captured via mobile phones, which might improve diagnostic accuracy. CONCLUSION: Mobile teledermatology using cellular phones is an innovative and convenient modality of providing dermatologic consultations for skin cancer screening.