Tolerability profile of topical cannabidiol and palmitoylethanolamide: a compilation of single-centre randomized evaluator-blinded clinical and in vitro studies in normal skin.

BACKGROUND: An increasing number of studies have investigated the adverse effect profile of oral cannabinoids; however, few studies have provided sufficient data on the tolerability of topical cannabinoids in human participants. AIM: To assess the tolerability profile of several commercial topical formulations containing cannabidiol (CBD) and palmitoylethanolamide (PEA) on the skin of healthy human participants. METHODS: Three human clinical trials and one in vitro study were conducted. The potential for skin irritation, sensitization and phototoxicity of several products, were assessed via patch testing on healthy human skin. The products assessed included two formulations containing CBD and PEA, one containing hemp seed oil and four concentrations of CBD alone. Ocular toxicity was tested using a traditional hen's egg chorioallantoic membrane model with three CBD, PEA and hemp seed oil formulations. RESULTS: There was no irritation or sensitization of the products evident via patch testing on healthy participants. Additionally, mild phototoxicity of a hemp seed oil product was found at the 48-h time point compared with the negative control. The in vitro experiment demonstrated comparable effects of cannabinoid products with historically nonirritating products. CONCLUSION: These specific formulations of CBD- and PEA-containing products are nonirritating and nonsensitizing in healthy adults, and further encourage similar research assessing their long-term safety and efficacy in human participants with dermatological diseases. There are some limitations to the study: (i) external validity may be limited as formulations from a single manufacturer were used for this study, while vast heterogeneity exists across unregulated, commercial CBD products on the market; and (ii) products were assessed only on normal, nondiseased human skin, and therefore extrapolation to those with dermatological diseases cannot be assumed.

The global burden of atopic dermatitis: lessons from the Global Burden of Disease Study 1990-2017.

BACKGROUND: The Global Burden of Disease (GBD) Study provides an annually updated resource to study disease-related morbidity and mortality worldwide. OBJECTIVES: Here we present the burden estimates for atopic dermatitis (AD), including data from inception of the GBD project in 1990 until 2017. METHODS: Data on the burden of AD were obtained from the GBD Study. RESULTS: Atopic dermatitis (AD) ranks 15th among all nonfatal diseases and has the highest disease burden among skin diseases as measured by disability-adjusted life-years (DALYs). Overall, the global DALY rate for AD in 1990 was 121 [95% uncertainty interval (UI) 65·4-201] and remained similar in 2017 at 123 (95% UI 66·8-205). The three countries with the highest DALY rates of AD were Sweden (327, 95% UI 178-547), the UK (284, 95% UI 155-478) and Iceland (277, 95% UI 149-465), whereas Uzbekistan (85·1, 95% UI 45·2-144), Armenia (85·1, 95% UI 45·8-143) and Tajikistan (85·1, 95% UI 46·1-143) ranked lowest. CONCLUSIONS: The global prevalence rate of AD has remained stable from 1990 to 2017. However, the distribution of AD by age groups shows a bimodal curve with the highest peak in early childhood, decreasing in prevalence among young adults, and a second peak in middle-aged and older populations. We also found a moderate positive correlation between a country's gross domestic product and disease burden. GBD data confirm the substantial worldwide burden of AD, which has remained stable since 1990 but shows significant geographical variation. Lifestyle factors, partially linked to affluence, are likely important disease drivers. However, the GBD methodology needs to be developed further to incorporate environmental risk factors, such as ultraviolet exposure, to understand better the geographical and age-related variations in disease burden.

Development of Patient Decision Aids for Plaque Psoriasis and Acne.

INTRODUCTION: Despite proven benefits in other medical specialties, there is a paucity of patient decision aids (PDAs) in dermatology. The present study developed online PDAs for acne and psoriasis, incorporating iterative patient and physician feedback, in accordance with International Patient Decision Aid Standards (IPDAS). DESIGN AND METHOD: Content was adapted from clinical practice guidelines and primary research and formatted for an 8th grade reading level. Feedback on content and format was obtained through focus groups with 15 psoriasis patients and survey with 34 acne patients. Feedback on presentation and clinical utility of the PDAs was gathered by survey from 51 physicians in Canada and the United States. Each data collection stage informed further development. RESULTS: Demand for decision support, and satisfaction with the PDAs was high among patients. Physicians were approving of content and expressed a strong interest in PDA use. CONCLUSION: Patients and physicians approve of the PDAs' content, format, and intended use. Online PDAs allow accessibility for patients and may reduce barriers to use for physicians.

The global burden of melanoma: results from the Global Burden of Disease Study 2015.

BACKGROUND: Despite recent improvements in prevention, diagnosis and treatment, vast differences in melanoma burden still exist between populations. Comparative data can highlight these differences and lead to focused efforts to reduce the burden of melanoma. OBJECTIVES: To assess global, regional and national melanoma incidence, mortality and disability-adjusted life year (DALY) estimates from the Global Burden of Disease Study 2015. METHODS: Vital registration system and cancer registry data were used for melanoma mortality modelling. Incidence and prevalence were estimated using separately modelled mortality-to-incidence ratios. Total prevalence was divided into four disease phases and multiplied by disability weights to generate years lived with disability (YLDs). Deaths in each age group were multiplied by the reference life expectancy to generate years of life lost (YLLs). YLDs and YLLs were added to estimate DALYs. RESULTS: The five world regions with the greatest melanoma incidence, DALY and mortality rates were Australasia, North America, Eastern Europe, Western Europe and Central Europe. With the exception of regions in sub-Saharan Africa, DALY and mortality rates were greater in men than in women. DALY rate by age was highest in those aged 75-79 years, 70-74 years and ≥ 80 years. CONCLUSIONS: The greatest burden from melanoma falls on Australasian, North American, European, elderly and male populations, which is consistent with previous investigations. These substantial disparities in melanoma burden worldwide highlight the need for aggressive prevention efforts. The Global Burden of Disease Study results can help shape melanoma research and public policy.

Shared decision making and patient decision aids in dermatology.

Shared decision making combines individual patient interests and values with clinical best evidence under the guiding principle of patient autonomy. Patient decision aids can support shared decision making and facilitate decisions that have multiple options with varying outcomes for which patients may attribute different values. Given the variable psychosocial impact of skin disease on individuals and relative uncertainty regarding best treatments and their adherence in many dermatological conditions, informed shared decision making, supported by patient decision aids, should constitute a central component of dermatological care.

Conflicts of interest in dermatology: a medical student and mentor perspective.

Conflict of interest (COI) in medicine is well defined, but is seldom discussed in the field of dermatology. This perspective sheds light on this topic in dermatology and provides suggestions on how better to approach COI in medical school and residency.

A North American perspective on dermoscopy: benefits, limitations, and grey zones.

Dermoscopy offers novel and cost-effective diagnostic information to guide patient care for melanocytic and non-melanocytic dermatoses. This article reviews the current use of dermoscopy, including its clinical benefits and limitations. Surveys of U.S. and Canadian dermatology residents have demonstrated a desire for improved dermoscopy teaching; an abundance of evidence calls for increasing its use in the clinical setting. Using the current evidence framework, North American dermatology training centers and professional societies should work to foster dermoscopy training and use by both dermatologists and other health care providers.

Clinical questions asked by medical students: a learning tool for dermatology rotations.

BACKGROUND/AIMS: To determine whether having medical students answer self-generated patient-specific questions in a clinical setting promotes learning. METHODS: Medical students rotating through dermatology clinics at the Denver Veterans' Affairs (VA) Medical Center were asked to formulate and answer one clinical question arising during patient encounters, and to complete a survey regarding their findings and experience. RESULTS: 49% (44/89) of rotating medical students completed the exercise. Self-generated questions frequently addressed therapy (61%, 27/44), prognosis (13%, 6/44), etiology/risk factors (7%, 3/44), and harm (5%, 2/44). The most frequently used sources of clinical information were journal abstracts/articles (55%, 24/44), UpToDate (50%, 22/44), websites (27%, 12/44) and printed textbooks (25%, 11/44). Medical students rated the impact of answers they obtained on a Likert scale of 1 (strongly disagree) to 5 (strongly agree) for the following: can be used to assist in patient's care (mean 4.1), improved care (mean 3.7), improved communication (mean 4.4), improved confidence in care (mean 4.2), improved knowledge (mean 4.6), and will improve future care (mean 4.5). CONCLUSIONS: Medical students report increased knowledge, confidence and patient care skills after completing a self-directed formal exercise consisting of formulating and answering a patient-specific clinical question.

Cochrane Skin Group systematic reviews are more methodologically rigorous than other systematic reviews in dermatology.

BACKGROUND: The Cochrane collaboration aims to produce high-quality systematic reviews. It is not known whether the methods used in producing Cochrane Skin Group (CSG) reviews result in higher quality reviews than other systematic reviews in dermatology. OBJECTIVES: To determine how the methodological quality of dermatological CSG reviews published in The Cochrane Library and in peer-reviewed journals compare with non-Cochrane systematic reviews. METHODS: Two blinded investigators independently assessed review quality using the 10-item Oxman and Guyatt scale. RESULTS: Thirty-eight systematic reviews (17 Cochrane reviews published in The Cochrane Library, 11 Cochrane reviews published in peer-reviewed journals and 10 non-Cochrane reviews published in peer-reviewed journals) were examined. The Cochrane Library reviews included quality of life (11/17 vs. 1/10, P = 0.014) and adverse outcomes (14/17 vs. 2/10, P = 0.003) more often than non-Cochrane reviews published in peer-reviewed journals. Cochrane reviews published in both peer-reviewed journals and The Cochrane Library were more likely to include comprehensive search strategies (11/11 and 17/17 vs. 6/10, P-values = 0.04 and 0.01), take steps to minimize selection bias (11/11 and 16/17 vs. 3/10, P-values = 0.003 and 0.001) and appropriately assess the validity of all included trials (10/11 and 16/17 vs. 4/10, P-values = 0.04 and 0.007) than non-Cochrane reviews. Overall, Cochrane reviews published both in peer-reviewed journals and in The Cochrane Library were assigned higher quality scores by reviewers than non-Cochrane reviews (median = 6.0 and 6.5 vs. 4.5, P-values = 0.01 and 0.002). CONCLUSIONS: The Cochrane Library systematic review methodology leads to higher quality reviews on dermatological topics.

Statins and fibrates for preventing melanoma.

BACKGROUND: Effective treatment for advanced melanoma is lacking. While no drug therapy currently exists for prevention of melanoma, in vitro, case-control, and animal model evidence suggest that lipid-lowering medications, commonly taken for high cholesterol, might prevent melanoma. OBJECTIVES: To assess the effects of statin or fibrate lipid-lowering medications on melanoma outcomes. SEARCH STRATEGY: We searched the Cochrane Skin Group Specialised Register (February 2003), CENTRAL (The Cochrane Library Issue 1, 2005), MEDLINE (to March 2003), EMBASE (to September 2003), CANCERLIT (to October 2002), Web of Science (to May 2003), and reference lists of articles. We approached study investigators and pharmaceutical companies for additional information (published or unpublished studies). SELECTION CRITERIA: Trials involving random allocation of study participants, where experimental groups used statins or fibrates and participants were enrolled for at least four years of therapy. DATA COLLECTION AND ANALYSIS: Three authors screened 109 abstracts of articles with titles of possible relevance. We then thoroughly examined the full text of 72 potentially relevant articles. We requested unpublished melanoma outcomes data from the corresponding author of each qualifying trial. MAIN RESULTS: We identified 16 qualifying randomised controlled trials (RCTs) (seven statin, nine fibrate). Thirteen of these trials (involving 62,197 participants) provided data on incident melanomas (six statin, seven fibrate). A total of 66 melanomas were reported in groups receiving the experimental drug and 86 in groups receiving placebo or other control therapies. For statin trials this translated to an odds ratio of 0.90 (95% confidence interval 0.56 to 1.44) and for fibrate trials an odds ratio of 0.58 (95% confidence interval 0.19 to 1.82). Subgroup analyses failed to show statistically significant differences in melanoma outcomes by gender, melanoma occurrence after two years of participation in trial, stage or histology, or trial funding. Subgroup analysis by type of fibrate or statin also failed to show statistically significant differences, except for the statin subgroup analysis which showed reduced melanoma incidence for lovastatin, based on one trial only (odds ratio 0.52, 95% confidence interval 0.27 to 0.99). AUTHORS' CONCLUSIONS: The melanoma outcomes data collected in this review of RCTs of statins and fibrates does not exclude the possibility that these drugs prevent melanoma. There was a 10% and 42% reduction for participants on statins and fibrates, respectively, however these results were not statistically significant. Until further evidence is established, limiting exposure to ultraviolet radiation remains the most effective way to reduce the risk of melanoma.