The Level of Agreement between Self-Assessments and Examiner Assessments of Melanocytic Nevus Counts: Findings from an Evaluation of 4548 Double Assessments.

Cutaneous melanoma (CM) is a candidate for screening programs because its prognosis is excellent when diagnosed at an early disease stage. Targeted screening of those at high risk for developing CM, a cost-effective alternative to population-wide screening, requires valid procedures to identify the high-risk group. Self-assessment of the number of nevi has been suggested as a component of such procedures, but its validity has not yet been established. We analyzed the level of agreement between self-assessments and examiner assessments of the number of melanocytic nevi in the area between the wrist and the shoulder of both arms based on 4548 study subjects in whom mutually blinded double counting of nevi was performed. Nevus counting followed the IARC protocol. Study subjects received written instructions, photographs, a mirror, and a "nevometer" to support self-assessment of nevi larger than 2 mm. Nevus counts were categorized based on the quintiles of the distribution into five levels, defining a nevus score. Cohen's weighted kappa coefficient (κ) was estimated to measure the level of agreement. In the total sample, the agreement between self-assessments and examiner assessments was moderate (weighted κ = 0.596). Self-assessed nevus counts were higher than those determined by trained examiners (mean difference: 3.33 nevi). The level of agreement was independent of sociodemographic and cutaneous factors; however, participants' eye color had a significant impact on the level of agreement. Our findings show that even with comprehensive guidance, only a moderate level of agreement between self-assessed and examiner-assessed nevus counts can be achieved. Self-assessed nevus information does not appear to be reliable enough to be used in individual risk assessment to target screening activities.

Global Tanning Bed Advertising: A Comparison of Legal Regulations on Three Continents.

Artificial ultraviolet radiation from tanning beds has been classified as carcinogenic by the International Agency for Research on Cancer in 2009. Several countries have subsequently introduced comprehensive legislation regulating commercial indoor tanning. Specific aspects of these regulations address tanning bed advertising and information requirements for tanning bed customers, which have been previously neglected in international comparisons of indoor tanning regulations. We performed a systematic search regarding legislation on these aspects in 131 legislative units across three continents (North America, Australia/New Zealand, Europe). The legal restrictions found varied widely in type and content. In 49 legislative units we identified total (n = 8) or partial legal bans (n = 41) on advertising for indoor tanning, while 64 legislative units enacted 5regulations that necessitate the dissemination of different types of specific health information to tanning bed customers. Nearly 40% of the legislative units of the study region lacked any legislation on these issues altogether. The heterogenous results emphasize the need for an international dialogue between health authorities and governments to harmonize the regulatory framework for tanning bed advertising and information requirements to a level better protecting the public from skin cancer. Our comprehensive international comparison can serve as a starting point for such a harmonization process that may ultimately protect the public worldwide from misleading tanning bed advertising.

Inter-Rater Agreement in Assessing Risk of Bias in Melanoma Prediction Studies Using the Prediction Model Risk of Bias Assessment Tool (PROBAST): Results from a Controlled Experiment on the Effect of Specific Rater Training.

Assessing the risk of bias (ROB) of studies is an important part of the conduct of systematic reviews and meta-analyses in clinical medicine. Among the many existing ROB tools, the Prediction Model Risk of Bias Assessment Tool (PROBAST) is a rather new instrument specifically designed to assess the ROB of prediction studies. In our study we analyzed the inter-rater reliability (IRR) of PROBAST and the effect of specialized training on the IRR. Six raters independently assessed the risk of bias (ROB) of all melanoma risk prediction studies published until 2021 (n = 42) using the PROBAST instrument. The raters evaluated the ROB of the first 20 studies without any guidance other than the published PROBAST literature. The remaining 22 studies were assessed after receiving customized training and guidance. Gwet's AC1 was used as the primary measure to quantify the pairwise and multi-rater IRR. Depending on the PROBAST domain, results before training showed a slight to moderate IRR (multi-rater AC1 ranging from 0.071 to 0.535). After training, the multi-rater AC1 ranged from 0.294 to 0.780 with a significant improvement for the overall ROB rating and two of the four domains. The largest net gain was achieved in the overall ROB rating (difference in multi-rater AC1: 0.405, 95%-CI 0.149-0.630). In conclusion, without targeted guidance, the IRR of PROBAST is low, questioning its use as an appropriate ROB instrument for prediction studies. Intensive training and guidance manuals with context-specific decision rules are needed to correctly apply and interpret the PROBAST instrument and to ensure consistency of ROB ratings.

Time Trend in SARS-CoV-2 Seropositivity, Surveillance Detection- and Infection Fatality Ratio until Spring 2021 in the Tirschenreuth County-Results from a Population-Based Longitudinal Study in Germany.

Herein, we provide results from a prospective population-based longitudinal follow-up (FU) SARS-CoV-2 serosurveillance study in Tirschenreuth, the county which was hit hardest in Germany in spring 2020 and early 2021. Of 4203 individuals aged 14 years or older enrolled at baseline (BL, June 2020), 3546 participated at FU1 (November 2020) and 3391 at FU2 (April 2021). Key metrics comprising standardized seroprevalence, surveillance detection ratio (SDR), infection fatality ratio (IFR) and success of the vaccination campaign were derived using the Roche N- and S-Elecsys anti-SARS-CoV-2 test together with a self-administered questionnaire. N-seropositivity at BL was 9.2% (1st wave). While we observed a low new seropositivity between BL and FU1 (0.9%), the combined 2nd and 3rd wave accounted for 6.1% new N-seropositives between FU1 and FU2 (ever seropositives at FU2: 15.4%). The SDR decreased from 5.4 (BL) to 1.1 (FU2) highlighting the success of massively increased testing in the population. The IFR based on a combination of serology and registration data resulted in 3.3% between November 2020 and April 2021 compared to 2.3% until June 2020. Although IFRs were consistently higher at FU2 compared to BL across age-groups, highest among individuals aged 70+ (18.3% versus 10.7%, respectively), observed differences were within statistical uncertainty bounds. While municipalities with senior care homes showed a higher IFR at BL (3.0% with senior care home vs. 0.7% w/o), this effect diminished at FU2 (3.4% vs. 2.9%). In April 2021 (FU2), vaccination rate in the elderly was high (>77.4%, age-group 80+).

Using the Prediction Model Risk of Bias Assessment Tool (PROBAST) to Evaluate Melanoma Prediction Studies.

Rising incidences of cutaneous melanoma have fueled the development of statistical models that predict individual melanoma risk. Our aim was to assess the validity of published prediction models for incident cutaneous melanoma using a standardized procedure based on PROBAST (Prediction model Risk Of Bias ASsessment Tool). We included studies that were identified by a recent systematic review and updated the literature search to ensure that our PROBAST rating included all relevant studies. Six reviewers assessed the risk of bias (ROB) for each study using the published "PROBAST Assessment Form" that consists of four domains and an overall ROB rating. We further examined a temporal effect regarding changes in overall and domain-specific ROB rating distributions. Altogether, 42 studies were assessed, of which the vast majority (n = 34; 81%) was rated as having high ROB. Only one study was judged as having low ROB. The main reasons for high ROB ratings were the use of hospital controls in case-control studies and the omission of any validation of prediction models. However, our temporal analysis results showed a significant reduction in the number of studies with high ROB for the domain "analysis". Nevertheless, the evidence base of high-quality studies that can be used to draw conclusions on the prediction of incident cutaneous melanoma is currently much weaker than the high number of studies on this topic would suggest.

Sun Protection and Tanning Behaviors in Caregivers: Prevalence, Determinants, and Associations with Children's Behaviors.

The association between skin cancer and ultraviolet radiation (UVR) is well established, and sun protection behavior represents an important preventative measure. In children, caregivers play a key role in this regard. The subject of this study was threefold: whether caregivers of 1 to 11 year-old children are more likely to use sun protection measures compared to non-caregivers, whether considering oneself a role model is associated with sun protection behaviors, and whether their sun protection and risk behaviors are related to children's behaviors. We used data from the 2020 wave of the National Cancer Aid Monitoring (NCAM) comprised of 4000 individuals (including 554 caregivers of at least one child aged 1−10 years) aged 16 to 65 years and living in Germany. Data were collected through telephone interviews between October and December 2020. No significant differences between caregivers and non-caregivers regarding sun protection and risk behaviors were identified (except tanning on vacation). In both groups, sun protection behaviors were deficient. Caregivers who considered themselves role models concerning sun safety were more likely to use sun protection measures (e.g., using sunscreen on the face: OR = 5.08, p < 0.001). In addition, caregivers' sun protection behaviors were positively associated with children's behaviors. Caregivers being highly protected against UVR were more likely to report the use of different measures by/in the child (mean = 4.03), compared to caregivers with medium (3.41) and low (2.97, p < 0.001) protection levels. However, we also found that caregivers' risk behavior was associated with children's reported risk behavior. For future prevention, it might be worth focusing on the aspect of caregivers serving as role models. A comprehensive public-health strategy is needed, including key figures such as pediatricians to prevent today's children from developing skin cancer in later life.

Reporting Quality of Studies Developing and Validating Melanoma Prediction Models: An Assessment Based on the TRIPOD Statement.

Transparent and accurate reporting is essential to evaluate the validity and applicability of risk prediction models. Our aim was to evaluate the reporting quality of studies developing and validating risk prediction models for melanoma according to the TRIPOD (Transparent Reporting of a multivariate prediction model for Individual Prognosis Or Diagnosis) checklist. We included studies that were identified by a recent systematic review and updated the literature search to ensure that our TRIPOD rating included all relevant studies. Six reviewers assessed compliance with all 37 TRIPOD components for each study using the published "TRIPOD Adherence Assessment Form". We further examined a potential temporal effect of the reporting quality. Altogether 42 studies were assessed including 35 studies reporting the development of a prediction model and seven studies reporting both development and validation. The median adherence to TRIPOD was 57% (range 29% to 78%). Study components that were least likely to be fully reported were related to model specification, title and abstract. Although the reporting quality has slightly increased over the past 35 years, there is still much room for improvement. Adherence to reporting guidelines such as TRIPOD in the publication of study results must be adopted as a matter of course to achieve a sufficient level of reporting quality necessary to foster the use of the prediction models in applications.

The Role of the Global Solar UV Index for Sun Protection of Children in German Kindergartens.

More than twenty-five years ago, the Global Solar UV index (UVI) was introduced as a simple means of visualizing the intensity of ultraviolet radiation and to alert people to the need for sun protection. In our survey, among directors of 436 kindergartens in southern Germany we investigated the level of awareness and knowledge about the UVI as well as the practical consequences for sun protection in kindergartens. Less than half of the directors (n = 208, 47.7%) had ever heard of the UVI, and only a small minority of them (n = 34, 8.7%) used the daily UVI information to adapt sun protective measures in their kindergartens. Detailed knowledge about the UVI was a rarity among the respondents. The proportion of respondents with self-perceived detailed UVI knowledge was five times higher than the actual knowledge assessed by an in-depth structured interview using open-ended questions about the UVI (14.2% vs. 2.8%). No clear relationship between UVI awareness, knowledge, and use and directors' age and gender was found. The UVI-related variables also showed no association with directors' knowledge of risk factors for skin cancer and their attitudes towards tanned skin. Overall, the results paint a sobering picture regarding the penetration of the UVI into sun protection policies of German kindergartens. Future public health campaigns should aim to increase the awareness and understanding of the UVI as well as its relevance for sun protection of children.

Spectrum Bias and Individual Strengths of SARS-CoV-2 Serological Tests-A Population-Based Evaluation.

Antibody testing for determining the SARS-CoV-2 serostatus was rapidly introduced in early 2020 and since then has been gaining special emphasis regarding correlates of protection. With limited access to representative samples with known SARS-CoV-2 infection status during the initial period of test development and validation, spectrum bias has to be considered when moving from a "test establishment setting" to population-based settings, in which antibody testing is currently implemented. To provide insights into the presence and magnitude of spectrum bias and to estimate performance measures of antibody testing in a population-based environment, we compared SARS-CoV-2 neutralization to a battery of serological tests and latent class analyses (LCA) in a subgroup (n = 856) of the larger population based TiKoCo-19 cohort (n = 4185). Regarding spectrum bias, we could proof notable differences in test sensitivities and specificities when moving to a population-based setting, with larger effects visible in earlier registered tests. While in the population-based setting the two Roche ELECSYS anti-SARS-CoV-2 tests outperformed every other test and even LCA regarding sensitivity and specificity in dichotomous testing, they didn't provide satisfying quantitative correlation with neutralization capacity. In contrast, our in-house anti SARS-CoV-2-Spike receptor binding domain (RBD) IgG-ELISA (enzyme-linked-immunosorbant assay) though inferior in dichotomous testing, provided satisfactory quantitative correlation and may thus represent a better correlate of protection. In summary, all tests, led by the two Roche tests, provided sufficient accuracy for dichotomous identification of neutralizing sera, with increasing spectrum bias visible in earlier registered tests, while the majority of tests, except the RBD-ELISA, didn't provide satisfactory quantitative correlations.

Sun Protection and Sunburn in Children Aged 1-10 Years in Germany: Prevalence and Determinants.

Seeking shade, the use of textile sun protection and sunscreen, and protecting one's eyes by wearing sunglasses are recommended sun protection measures in children. We aimed to quantify the use of these measures as well as the prevalence of sunburn in children aged 1 to 10 years in Germany and to identify their determinants. Data collected via telephone interviews in a nationwide sample of 554 parents or caregivers in family were analyzed. Use of sunscreen was the most common measure applied (77.8%), while sunglasses were least frequently used (12.5%). The prevalence of sunburn during the past year was 21.8%, and it was positively associated with children's age. The use of sun protection measures was significantly associated with the age and skin color of the child, while characteristics and tanning behaviors of the caregivers only played a minor role. The use of sun protection measures was higher when caregivers perceived themselves as a role model (Odds Ratio (OR) = 4.33, p < 0.001). Our nationwide data show that there remains a need for the improved use of sun protection measures, especially in children aged 7 to 10 years. In educational material, parents should be encouraged to become positive role models for their children regarding sun protection.

Estimates and Determinants of SARS-Cov-2 Seroprevalence and Infection Fatality Ratio Using Latent Class Analysis: The Population-Based Tirschenreuth Study in the Hardest-Hit German County in Spring 2020.

SARS-CoV-2 infection fatality ratios (IFR) remain controversially discussed with implications for political measures. The German county of Tirschenreuth suffered a severe SARS-CoV-2 outbreak in spring 2020, with particularly high case fatality ratio (CFR). To estimate seroprevalence, underreported infections, and IFR for the Tirschenreuth population aged ≥14 years in June/July 2020, we conducted a population-based study including home visits for the elderly, and analyzed 4203 participants for SARS-CoV-2 antibodies via three antibody tests. Latent class analysis yielded 8.6% standardized county-wide seroprevalence, a factor of underreported infections of 5.0, and 2.5% overall IFR. Seroprevalence was two-fold higher among medical workers and one third among current smokers with similar proportions of registered infections. While seroprevalence did not show an age-trend, the factor of underreported infections was 12.2 in the young versus 1.7 for ≥85-year-old. Age-specific IFRs were <0.5% below 60 years of age, 1.0% for age 60-69, and 13.2% for age 70+. Senior care homes accounted for 45% of COVID-19-related deaths, reflected by an IFR of 7.5% among individuals aged 70+ and an overall IFR of 1.4% when excluding senior care home residents from our computation. Our data underscore senior care home infections as key determinant of IFR additionally to age, insufficient targeted testing in the young, and the need for further investigations on behavioral or molecular causes of the fewer infections among current smokers.

"I've Heard of It, Yes, but I Can't Remember What Exactly It Was"-A Qualitative Study on Awareness, Knowledge, and Use of the UV Index.

Pharmacists and pharmaceutical technicians play an important role in counselling customers regarding sunscreen use and sun protection measures. A potentially helpful tool that can be used during counselling is the ultraviolet index (UVI), which informs individuals when and what sun protection measures are needed at a specific place and time. Our aim in this qualitative study was to explore awareness, knowledge, and use of the UVI during counselling in pharmacies. We used semi-structured interviews with pharmacists and pharmaceutical technicians (n = 20) to answer our research questions. Interviews were audiotaped, transcribed verbatim, and analyzed using qualitative content analysis. During the interviews pharmacists and pharmaceutical technicians revealed a lot of uncertainty and lack of knowledge regarding the UVI. Eight professionals were able to give a correct definition of UVI. Amongst others, the UVI was confused with sun protection factor. Overall, the UVI was hardly used during the counselling of customers. The UVI was developed to provide guidance when which type of sun protection is required to avoid detrimental effects of ultraviolet radiation. For effective implementation, both the general population and health professionals (e.g., pharmacists) have to increase their knowledge about the UVI. This would strengthen its use during professional counselling in pharmacies and may help to reduce the incidence of skin cancer over the long term.

Risk Prediction Models for Melanoma: A Systematic Review on the Heterogeneity in Model Development and Validation.

The rising incidence of cutaneous melanoma over the past few decades has prompted substantial efforts to develop risk prediction models identifying people at high risk of developing melanoma to facilitate targeted screening programs. We review these models, regarding study characteristics, differences in risk factor selection and assessment, evaluation, and validation methods. Our systematic literature search revealed 40 studies comprising 46 different risk prediction models eligible for the review. Altogether, 35 different risk factors were part of the models with nevi being the most common one (n = 35, 78%); little consistency in other risk factors was observed. Results of an internal validation were reported for less than half of the studies (n = 18, 45%), and only 6 performed external validation. In terms of model performance, 29 studies assessed the discriminative ability of their models; other performance measures, e.g., regarding calibration or clinical usefulness, were rarely reported. Due to the substantial heterogeneity in risk factor selection and assessment as well as methodologic aspects of model development, direct comparisons between models are hardly possible. Uniform methodologic standards for the development and validation of risk prediction models for melanoma and reporting standards for the accompanying publications are necessary and need to be obligatory for that reason.

The extent of public awareness, understanding and use of the Global Solar UV index as a worldwide health promotion instrument to improve sun protection: protocol for a systematic review.

INTRODUCTION: (Over)exposure to ultraviolet radiation is a major risk factor for skin cancer. The Global Solar Ultraviolet Index (UVI) was introduced by the WHO and partner organisations in 1995 as a simple measure of the intensity of solar UV radiation, providing guidance for the population to use appropriate sun protective measures. Little is known about the impact of the UVI on actual sun protection behaviour. Our systematic review aims to assess global levels of awareness, understanding and use of the UVI as prerequisites for the preventive effectiveness of this public health tool. METHODS AND ANALYSIS: Systematic searches will be performed in 10 electronic literature databases including Medline, Scopus and Web of Science-Core Collection, two clinical trials registries and at least two grey literature databases (OpenGrey, Bielefeld Academic Search Engine). Additional literature sources will be retrieved using hand search of reference lists of included studies and snowballing methods. We will include studies with all types of quantitative study designs and participants reporting on at least one outcome in the three main categories (i) awareness, (ii) understanding and (iii) use of the UVI. We will assess the risk of bias within studies with an abbreviated version of the AXIS tool, designed specifically for cross-sectional studies. As we expect large heterogeneity in outcomes, we will conduct a narrative synthesis of results instead of a meta-analysis. ETHICS AND DISSEMINATION: Ethical approval and patient consent are not required as this is a systematic review based on published studies. The results of this study will be published in an international peer-reviewed journal. PROSPERO REGISTRATION NUMBER: CRD42018093693.

Public Health Messages Associated with Low UV Index Values Need Reconsideration.

Overexposure to ultraviolet (UV) radiation is the main modifiable risk factor for skin cancer. The Global Solar Ultraviolet Index (UVI) was introduced as a tool to visualize the intensity of UV radiation on a certain day, which should enable and encourage people to take appropriate protective measures. The 'low' exposure category of the UVI, defined by a rounded UVI value of 0, 1 or 2, was linked to the health message 'No protection required' by the World Health Organization and partner organizations. However, published evidence corroborating this advice is not available. To evaluate the erythemal risk of low UVI days, we analyzed 14,431 daily time series of ambient erythemal irradiance data measured at nine stations of the German solar UV monitoring network during the years 2007-2016. We analyzed the proportion of days in the sample for which ambient erythemal doses calculated for various time intervals exceed average minimal erythemal doses (MEDs) of the Fitzpatrick skin phototypes I-VI to assess the potential for erythema arising from sun exposure on days with low UVI values. Additionally, we calculated for each day the minimum exposure duration needed to receive one MED. Our results indicate that on days with a UVI value of 0, risk of erythema is indeed negligible. Conversely, the abovementioned health message appears misleading when melano-compromised individuals (skin type I and II) spend more than 1.5 hours outdoors on days with a UVI value of 2. Under rare circumstances of prolonged exposure, MEDs of the two most sensitive skin types can also be exceeded even on days with a UVI value of 1. Hence, current WHO guidance for sun protection on days with low UVI values needs reconsideration.

Erythemal UV Radiation on Days with Low UV Index Values-an Analysis of Data from the German Solar UV Monitoring Network over a Ten-year Period.

According to the World Health Organization and partner organizations, no protection against ultraviolet (UV) radiation is required on days with "low" values (i.e., values <3) of the Global Solar Ultraviolet Index (UVI). Erythemal irradiance (Eer ) data of such days were analyzed to evaluate this claim. Measurements from 9 stations of the German solar UV monitoring network from 2007 to 2016 yielded 14,431 daily Eer time series of low UVI days. Erythemal doses for certain fixed time intervals-acquired from measurements on horizontal planes-were compared with the average minimal erythemal dose (MED) of skin phototype II. Doses from days with rounded UVI values of 0 were insufficient to induce erythema and even on days with rounded UVI values of 1 doses exceeding 1 MED of skin type II could only be acquired under very specific circumstances of prolonged exposure. Conversely, sun exposure on days with rounded UVI values of 2 can indeed provide doses sufficient to induce erythema in skin type II after two hours around noon. In conclusion, our analyses do not support the claim of harmlessness currently associated with the entire low UVI exposure category in public guidance on interpretation of the UVI.

Shedding Light on the Shade: How Nurseries Protect Their Children from Ultraviolet Radiation.

Minimizing exposure to ultraviolet radiation (UVR) is strongly recommended as the most important primary prevention measure regarding skin cancer. The responsibility for adequate sun protection of young children lies with their parents and external caregivers. Since a high proportion of 3- to 6-year-old children in Germany attend nurseries, the practice of sun protection in this setting was assessed. A survey was conducted in 246 nurseries in southern Germany during spring and summer of 2014 and 2015. Shade coverage in the outdoor area of the nursery was assessed by study team members and UVR protective behavior of staff was assessed by an interview with the directors. On average, 52% of the entire outdoor area and 65% of the children's outdoor play area were covered by shade, with a significant difference between nurseries of different sizes, pointing to a better shade coverage in larger nurseries. The daily outdoor stay was not regularly scheduled before or after peak sun intensity hours around noon to avoid intense UVR exposure. General sun protection rules were present in the majority of the nurseries and addressed predominantly wearing sunhats and applying sunscreen. Our findings show that current sun protection recommendations for children are only partially met in nurseries and indicate a lower level of sun protection in small institutions. Especially, avoidance of excessive exposure to UVR around noon and the importance of shade provision over play structures needs to be emphasized in future information campaigns.

Implications of Low Levels of the UV Index for Sun Protection.

A Global Solar Ultraviolet Index (UVI) value of 2 is generally linked to the health message 'You can safely stay outside!' To examine whether this is sound advice for all skin types and even for prolonged periods spent outside we used erythemal irradiance data of all 136 days during the study period from 2014 till 2016 with such a UVI measured by the German Federal Office for Radiation Protection (BfS) in Munich, Germany. A comparison between the ambient erythemal doses calculated for various time intervals and minimal erythemal doses (MEDs) of the Caucasian skin types I-IV led us to a critical reappraisal of the above health message. Specifically, the message might be misleading if people with a fair complexion want to spend several hours outside, because without any protective measures the doses received can be sufficient to induce erythema. We thus recommend an amendment of the health message related to a safe level of the UVI and, moreover, generally tailoring UVI-related health messages to different skin types. Currently, these messages do not seem to be strictly evidence based, which might be one reason for the unexpected result of our analysis.