Robert P. Dellavalle

The Global Burden of Skin Disease in 2010: An Analysis of the Prevalence and Impact of Skin Conditions

The Global Burden of Disease (GBD) Study 2010 estimated the GBD attributable to 15 categories of skin disease from 1990 to 2010 for 187 countries. For each of the following diseases, we performed systematic literature reviews and analyzed resulting data: eczema, psoriasis, acne vulgaris, pruritus, alopecia areata, decubitus ulcer, urticaria, scabies, fungal skin diseases, impetigo, abscess, and other bacterial skin diseases, cellulitis, viral warts, molluscum contagiosum, and non-melanoma skin cancer. We used disability estimates to determine nonfatal burden. Three skin conditions, fungal skin diseases, other skin and subcutaneous diseases, and acne were in the top 10 most prevalent diseases worldwide in 2010, and eight fell into the top 50; these additional five skin problems were pruritus, eczema, impetigo, scabies, and molluscum contagiosum. Collectively, skin conditions ranged from the 2nd to 11th leading cause of years lived with disability at the country level. At the global level, skin conditions were the fourth leading cause of nonfatal disease burden. Using more data than has been used previously, the burden due to these diseases is enormous in both high- and low-income countries. These results argue strongly to include skin disease prevention and treatment in future global health strategies as a matter of urgency.

Mobile medical and health apps: state of the art, concerns, regulatory control and certification

This paper examines the state of the art in mobile clinical and health-related apps. A 2012 estimate puts the number of health-related apps at no fewer than 40,000, as healthcare professionals and consumers continue to express concerns about the quality of many apps, calling for some form of app regulatory control or certification to be put in place. We describe the range of apps on offer as of 2013, and then present a brief survey of evaluation studies of medical and health-related apps that have been conducted to date, covering a range of clinical disciplines and topics. Our survey includes studies that highlighted risks, negative issues and worrying deficiencies in existing apps. We discuss the concept of ‘apps as a medical device’ and the relevant regulatory controls that apply in USA and Europe, offering examples of apps that have been formally approved using these mechanisms. We describe the online Health Apps Library run by the National Health Service in England and the calls for a vetted medical and health app store. We discuss the ingredients for successful apps beyond the rather narrow definition of ‘apps as a medical device’. These ingredients cover app content quality, usability, the need to match apps to consumers’ general and health literacy levels, device connectivity standards (for apps that connect to glucometers, blood pressure monitors, etc.), as well as app security and user privacy. ‘Happtique Health App Certification Program’ (HACP), a voluntary app certification scheme, successfully captures most of these desiderata, but is solely focused on apps targeting the US market. HACP, while very welcome, is in ways reminiscent of the early days of the Web, when many “similar” quality benchmarking tools and codes of conduct for information publishers were proposed to appraise and rate online medical and health information. It is probably impossible to rate and police every app on offer today, much like in those early days of the Web, when people quickly realised the same regarding informational Web pages. The best first line of defence was, is, and will always be to educate consumers regarding the potentially harmful content of (some) apps.

Lovastatin-induced apoptosis in human melanoma cell lines.

The cholesterol-lowering medications, statins, inhibit cellular proliferation and induce apoptosis in an array of cancer cell lines, including melanoma. We investigated the apoptotic mechanism of lovastatin on human melanoma cell lines in vitro. The cytotoxicity of statins on multiple cell lines was examined by Cell Titer 96™ Aqueous One solution cell proliferation assay (MTS assay). Apoptosis was assayed by ethidium bromide and acridine orange morphologic assays, an Annexin V apoptosis detection kit and active caspase 3 assays. Farnesyl pyrophosphate and geranylgeranyl pyrophosphate add-back experiments were performed to better define the molecular mechanisms mediating lovastatin cytotoxicity. Lovastatin caused cytotoxicity in human and murine melanoma cells, but did not induce toxicity in an epidermoid carcinoma cell line A431. For human melanoma cells, lovastatin precipitated cell rounding, increased the percentage of apoptotic cells detected by ethidium bromide and acridine orange staining and by the Annexin V apoptosis detection kit, and resulted in a 50-fold increase in active caspase 3, corroborating that lovastatin induced apoptosis. Adding back geranylgeranyl pyrophosphate, but not farnesyl pyrophosphate, reversed the effects of lovastatin in A375 cells. Of the five statins tested, pravastatin was least effective in killing melanoma cells. Lovastatin induced caspase-dependent apoptosis in multiple melanoma cell lines via a geranylation-specific mechanism. This study supports a possible role of lovastatin as a therapeutic, adjuvant or chemopreventative agent for melanoma.

Legislation Restricting Access to Indoor Tanning Throughout the World

OBJECTIVE To compile current legislation of indoor tanning throughout the world and compare them with existing legislation found in 2003. DESIGN Cross-sectional study. SETTING International. PARTICIPANTS All nations with legislation regarding access to indoor tanning found through web-based Internet search. MAIN OUTCOME MEASURES Number of nations with legislation and changes to laws regarding access to indoor tanning since 2003. RESULTS The number of countries with nationwide indoor tanning legislation restricting youth 18 years or younger increased from 2 countries in 2003 to 11 countries in 2011. Six states or territories in Australia restricted indoor tanning in all minors; a province and a region in Canada implemented youth tanning laws; and 8 states, in addition to 3 preexisting state laws, in the United States implemented indoor tanning legislation since 2003. CONCLUSION Since 2003, access to indoor tanning has become increasingly restricted around the world.

Global Burden of Skin Disease as Reflected in Cochrane Database of Systematic Reviews

IMPORTANCE Research prioritization should be guided by impact of disease. OBJECTIVE To determine whether systematic reviews and protocol topics in Cochrane Database of Systematic Reviews (CDSR) reflect disease burden, measured by disability-adjusted life years (DALYs) from the Global Burden of Disease (GBD) 2010 project. DESIGN, SETTING, AND PARTICIPANTS Two investigators independently assessed 15 skin conditions in the CDSR for systematic review and protocol representation from November 1, 2013, to December 6, 2013. The 15 skin diseases were matched to their respective DALYs from GBD 2010. An official publication report of all reviews and protocols published by the Cochrane Skin Group (CSG) was also obtained to ensure that no titles were missed. There were no study participants other than the researchers, who worked with databases evaluating CDSR and GBD 2010 skin condition disability data. MAIN OUTCOMES AND MEASURES Relationship of CDSR topic coverage (systematic reviews and protocols) with percentage of total 2010 DALYs, 2010 DALY rank, and DALY percentage change from 1990 to 2010 for 15 skin conditions. RESULTS All 15 skin conditions were represented by at least 1 systematic review in CDSR; 69% of systematic reviews and 67% of protocols by the CSG covered the 15 skin conditions. Comparing the number of reviews/protocols and disability, dermatitis, melanoma, nonmelanoma skin cancer, viral skin diseases, and fungal skin diseases were well matched. Decubitus ulcer, psoriasis, and leprosy demonstrated review/protocol overrepresentation when matched with corresponding DALYs. In comparison, acne vulgaris, bacterial skin diseases, urticaria, pruritus, scabies, cellulitis, and alopecia areata were underrepresented in CDSR when matched with corresponding DALYs. CONCLUSIONS AND RELEVANCE Degree of representation in CDSR is partly correlated with DALY metrics. The number of published reviews/protocols was well matched with disability metrics for 5 of the 15 studied skin diseases, while 3 skin diseases were overrepresented, and 7 were underrepresented. Our results provide high-quality and transparent data to inform future prioritization decisions.

Long-term Efficacy of Topical Fluorouracil Cream, 5%, for Treating Actinic Keratosis: A Randomized Clinical Trial

IMPORTANCE Topical fluorouracil was demonstrated to be effective in reducing the number of actinic keratoses (AKs) for up to 6 months, but no randomized trials studied its long-term efficacy. OBJECTIVE To evaluate the long-term efficacy of a single course of fluorouracil cream, 5%, for AK treatment. DESIGN, SETTING, AND PARTICIPANTS The Veterans Affairs Keratinocyte Carcinoma Chemoprevention (VAKCC) trial was a randomized, double-blinded, placebo-controlled trial with patients from dermatology clinics at 12 VA medical centers recruited from 2009 to 2011 and followed up until 2013. Our study population comprised 932 veterans with 2 or more keratinocyte carcinomas in the 5 years prior to enrollment. The mean follow-up duration was 2.6 years in both treatment and control groups. INTERVENTIONS Participants applied either topical fluorouracil cream, 5% (n = 468), or vehicle control cream (n = 464) to the face and ears twice daily for up to 4 weeks. MAIN OUTCOMES AND MEASURES This study reports on AK counts and treatments, which were secondary outcomes of the VAKCC trial. Actinic keratoses on the face and ears were counted by study dermatologists at enrollment and at study visits every 6 months. The number of spot treatments for AKs on the face and ears at semiannual study visits and in between study visits was recorded. RESULTS The number of AKs on the face and ears per participant was not different between the fluorouracil and control groups at randomization (11.1 vs 10.6, P > .10). After randomization, the fluorouracil group had fewer AKs compared with the control group at 6 months (3.0 vs 8.1, P < .001) and for the overall study duration (P < .001). The fluorouracil group also had higher complete AK clearance rates (38% vs 17% at 6 months) and fewer spot treatments at 6-month intervals, at study visits, and in between study visits during the trial (P < .01 for all). The fluorouracil group took longer to require the first spot AK treatment (6.2 months) compared with the control group (6.0 months) (hazard ratio, 0.69; 95% CI, 0.60-0.79). The number of hypertrophic AKs was not different between the 2 groups overall (P = .60), although there were fewer hypertrophic AKs in the fluorouracil group at 6 months (0.23 vs 0.41) (P = .05). CONCLUSIONS AND RELEVANCE Our results indicate that a single course of fluorouracil cream, 5%, effectively reduces AK counts and the need for spot treatments for longer than 2 years. TRIAL REGISTRATION clinicaltrials.gov Identifier:NCT00847912.

Melanoma chemoprevention: a role for statins or fibrates?

Although numerous second-generation isoprenylation inhibitors are proposed or under investigation for the treatment and/or prevention of cancer (eg, R115777, SCH 66336, L-778,123, BMS-214662), the chemotherapeutic and chemopreventive potential of commonly prescribed first-generation isoprenylation inhibitors, the statins, and other classes of lipid-lowering medications, the fibrates, has yet to be seriously explored. Two lipid-lowering medications, lovastatin and gemfibrozil, have been associated with a decreased incidence of melanoma in large, prospective, randomized, double-blind, placebo-controlled clinical cardiology trials. This article reviews melanoma biology and the clinical evidence for the use of lipid-lowering medications for melanoma chemoprevention and/or adjuvant chemotherapy.

The epidemiology of acne vulgaris in late adolescence

Importance Acne vulgaris is the most common skin condition affecting late adolescents across the globe. Although prior studies have evaluated epidemiologic patterns of acne vulgaris in various ethnicities and regions, adequate understanding of the worldwide burden of the disease associated with patients in their late adolescence (15–19-year olds) remains lacking. Objective To assess the global burden of the disease associated with acne vulgaris for late adolescents (15–19-year olds) and provide an overview of the epidemiology, pathophysiology, and treatment options for acne in this population. Design Database summary study. Setting Global Burden of Disease Study 2010 database. Participants Global Burden of Disease regions comprised countries with prevalence of acne vulgaris between the ages of 15 and 19 years. Main outcomes and measures Geographic region-level disability-adjusted life year rates (per 100,000 persons) associated with acne vulgaris in years 1990 through 2010. Median percentage change in disability-adjusted life year rates was estimated for each region across the specified study period. Conclusion and relevance Acne vulgaris-associated disease burden exhibits global distribution and has continued to grow in prevalence over time within this population. This continued growth suggests an unmet dermatologic need worldwide for this disorder and potential opportunities for improved access and delivery of dermatologic care. Our analysis of the literature reveals numerous opportunities for enhanced patient care. To that end, we highlight some of the effective and promising treatments currently available and address important factors, such as sex, nationality, genetics, pathophysiology, and diet, as they relate to acne vulgaris in late adolescence.

Tanning and increased nevus development in very-light-skinned children without red hair.

OBJECTIVE To examine the relationship between tanning and nevus development in very-light-skinned children. DESIGN Prospective cohort nested within a randomized controlled trial. Skin examinations in 3 consecutive years (2004, 2005, and 2006) included full-body counts of nevi, skin color and tanning measurement using colorimetry, and hair and eye color evaluation by comparison with charts. Telephone interviews of parents provided sun exposure, sun protection, and sunburn history. SETTING Large managed-care organization and private pediatric offices in the Denver, Colorado, metropolitan area. PARTICIPANTS A total of 131 very-light-skinned white children without red hair and 444 darker-skinned white children without red hair born in Colorado in 1998. MAIN OUTCOME MEASURES Full-body nevus counts at ages 6 to 8 years. RESULTS Among very-light-skinned white children, geometric mean numbers of nevi for minimally tanned children were 14.8 at age 6 years; 18.8 at age 7 years; and 22.3 at age 8 years. Mean numbers of nevi for tanned children were 21.2 at age 6 years; 27.9 at age 7 years; and 31.9 at age 8 years. Differences in nevus counts between untanned and tanned children were statistically significant at all ages (P < .05 for all comparisons). The relationship between tanning and number of nevi was independent of the childs hair and eye color, parent-reported sun exposure, and skin phototype. Among darker-skinned white children, there was no relationship between tanning and nevi. CONCLUSIONS Very-light-skinned children who tan (based on objective measurement) develop more nevi than children who do not tan. These results suggest that light-skinned children who develop tans may be increasing their risk for developing melanoma later in life.

Melanocytic nevus development in Colorado children born in 1998: a longitudinal study.

OBJECTIVE To describe the development of nevi from 3 to 8 years of age in a birth cohort of children in Colorado. DESIGN Longitudinal observational study. SETTING Large managed care organization and university and private primary care practices. PARTICIPANTS Annual convenience samples of children born in 1998 (range, n = 137 to n = 870) (participation rates, 18.8%-76.0%). We recruited children through the managed care organization, private primary care practices, and community settings. MAIN OUTCOME MEASURES Total whole body nevus counts, counts by nevus diameter (< 2, 2 to < 5, or > or = 5 mm), and counts for chronically and intermittently exposed body sites. RESULTS Non-Hispanic white children had significantly more nevi than did other racial/ethnic groups and developed an average of 4 to 6 new nevi per year from 3 to 8 years of age. Non-Hispanic white boys had significantly more nevi than did girls beginning at 6 years of age (median, 21 [interquartile range, 28] vs 17 [17]; P = .002). This difference was due to nevi of less than 2 mm and nevi in chronically exposed body sites. Development of new nevi leveled off in chronically exposed body sites at 7 years of age and at a higher level for boys than girls. CONCLUSIONS Children in Colorado developed more small nevi and fewer large nevi compared with children in other regions of the world, highlighting the importance of studying nevus development in various locations where sun exposure patterns and behavioral norms vary. The sex difference in nevus development could be owing to variation in sun exposure and/or a biological predisposition of boys to develop more nevi. Studies of nevus development can aid in the understanding of the complicated relationship between nevus development and malignant melanoma.