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Objectives: Observational studies are not subject to the same requirements as randomized controlled trials, such as registration or publishing a protocol. The aim of this scoping review was to estimate the registration rate of observational studies in leading peer-reviewed medicine journals and to evaluate whether protocols were available in the public domain., Study Design and Setting: In March 2023, we searched OVID Medline for observational studies published in 2022 in the top five general medicine journals according to impact factor (The Lancet, The British Medical Journal (BMJ), The Journal of the American Medical Association, The New England Journal of Medicine, and Annals of Internal Medicine). We defined an observational study as a cohort study, a case-control study, a cross-sectional study, or a case series. Information on i) the proportion of observational studies that have been registered and ii) the proportion of observational studies that have a protocol available in the public domain was extracted from a random sample of studies., Results: Our search identified 699 studies; 290 studies were selected as full text, and a random sample of 200 studies was included. For half of the studies, the first author worked at a US institution. Most studies were cohort studies (n = 126, 63.0%) and used administrative healthcare records, electronic healthcare records, and registries. Of the 200 observational studies, 20 (10.0%) were registered. Among those, 14 were prospectively registered. Twenty-four studies (12.0%) had a protocol available in the public domain. Studies that were registered or had a protocol, were more frequently published in the BMJ (n = 12/28, 42.9%), had a first author working in the UK (n = 10/28, 35.7%) and used electronic health care records (n = 13/28, 46.4%) compared to studies with no registration and no protocol., Conclusion: The rate of prospectively registered observational studies is worryingly low. Prospective registration of observational studies should be encouraged and standardized to ensure transparency in clinical research and reduce research waste., Competing Interests: Declaration of competing interest The authors declare no competing interest., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Nested case-control (NCC) designs are efficient for developing and validating prediction models that use expensive or difficult-to-obtain predictors, especially when the outcome is rare. Previous research has focused on how to develop prediction models in this sampling design, but little attention has been given to model validation in this context. We therefore aimed to systematically characterize the key elements for the correct evaluation of the performance of prediction models in NCC data., Methods: We proposed how to correctly evaluate prediction models in NCC data, by adjusting performance metrics with sampling weights to account for the NCC sampling. We included in this study the C-index, threshold-based metrics, Observed-to-expected events ratio (O/E ratio), calibration slope, and decision curve analysis. We illustrated the proposed metrics with a validation of the Breast and Ovarian Analysis of Disease Incidence and Carrier Estimation Algorithm (BOADICEA version 5) in data from the population-based Rotterdam study. We compared the metrics obtained in the full cohort with those obtained in NCC datasets sampled from the Rotterdam study, with and without a matched design., Results: Performance metrics without weight adjustment were biased: the unweighted C-index in NCC datasets was 0.61 (0.58-0.63) for the unmatched design, while the C-index in the full cohort and the weighted C-index in the NCC datasets were similar: 0.65 (0.62-0.69) and 0.65 (0.61-0.69), respectively. The unweighted O/E ratio was 18.38 (17.67-19.06) in the NCC datasets, while it was 1.69 (1.42-1.93) in the full cohort and its weighted version in the NCC datasets was 1.68 (1.53-1.84). Similarly, weighted adjustments of threshold-based metrics and net benefit for decision curves were unbiased estimates of the corresponding metrics in the full cohort, while the corresponding unweighted metrics were biased. In the matched design, the bias of the unweighted metrics was larger, but it could also be compensated by the weight adjustment., Conclusions: Nested case-control studies are an efficient solution for evaluating the performance of prediction models that use expensive or difficult-to-obtain biomarkers, especially when the outcome is rare, but the performance metrics need to be adjusted to the sampling procedure., (© 2024. The Author(s).)

Background: Actinic keratosis (AK) is a common dermatological condition, and among the most common dermatological diagnoses in older populations. Although the prevalence of AK depends on demographic and environmental factors, little is known about the global context of AK., Objectives: To provide a comprehensive and updated analysis of the global prevalence rate and incidence of AK in the general population through a systematic review and meta-analysis, and - through subgroup analyses - to identify high-risk phenotypes, demographic and lifestyle risk factors and regional variations in disease prevalence., Methods: A systematic search of Embase, MEDLINE, Web of Science and Google Scholar was performed on 20 May 2022. Two reviewers independently screened and assessed the quality of each study using a validated critical appraisal checklist. Epidemiological measurements (e.g. prevalence) from individual studies performed in the general population were then pooled in a random-effects meta-analysis. Subgroup analyses (i.e. population age, geographical region, occupation, sex and study quality) were conducted., Results: Of the 65 articles that made it through the full-text screening, 60 reported a point prevalence. A meta-analysis of these articles yielded an overall point prevalence of 14% [95% confidence interval (CI) 14-15]. In further analyses, the calculated prevalence rate varied depending on subgroup. The pooled incidence rate from the seven eligible studies analysed was 1928 per 100 000 person-years (PY; 95% CI -439 to 4294)., Conclusions: This comprehensive meta-analysis provides an updated global prevalence rate of AK of 14%, indicating a significant worldwide disease burden. The incidence rate of AK was found to be 1928 per 100 000 PY, emphasizing a growing public health concern. However, high heterogeneity among studies suggests that various factors influence the AK prevalence rate, necessitating further research to understand the observed differences., (© The Author(s) 2023. Published by Oxford University Press on behalf of British Association of Dermatologists.)

Background: There is lack of nationwide data on the cumulative incidence and timing of subsequent cutaneous squamous cell carcinomas (cSCCs) among patients with a first cSCC., Objective: To investigate the cumulative incidence and timing of subsequent cSCCs., Methods: Patients with a first cSCC in 2007/2008 from the Netherlands Cancer Registry were linked to the Netherlands Pathology Registry for subsequent cSCCs and the Netherlands Organ Transplant Registry. Cumulative incidence function curves were calculated for subsequent cSCCs and stratified for immune status., Results: Among the 12,345 patients, second to sixth cSCC occurred in 4325, 2010, 1138, 739, and 501 patients, with median time intervals of 1.4, 1.2, 0.9, 0.6, and 0.5 years after the previous cSCC, respectively. The cumulative incidence of a subsequent cSCC at 5 years increased from 28% to 67% for the second to sixth cSCC. For solid organ transplant recipients, the cumulative incidences increased from 74% to 92% and from 41% to 64% for patients with hematologic malignancy., Limitations: Only histopathologically confirmed cSCCs were included., Conclusion: The risk of a subsequent cSCC steeply rises with the number of prior cSCCs and immune status, while the time interval decreases. This can support more informed decisions about follow-up management., Competing Interests: Conflicts of interest Dr Wakkee served as an advisory board member on advanced cSCC for Sanofi Genzyme, and received financial reimbursement for her participation. All other authors declare no conflicts of interest., (Copyright © 2023 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.)

Background: Cutaneous squamous cell carcinoma (cSCC) is a common skin cancer, affecting more than 2 million people worldwide yearly and metastasising in 2-5% of patients. However, current clinical staging systems do not provide estimates of absolute metastatic risk, hence missing the opportunity for more personalised treatment advice. We aimed to develop a clinico-pathological model that predicts the probability of metastasis in patients with cSCC., Methods: Nationwide cohorts from (1) all patients with a first primary cSCC in The Netherlands in 2007-2008 and (2) all patients with a cSCC in 2013-2015 in England were used to derive nested case-control cohorts. Pathology records of primary cSCCs that originated a loco-regional or distant metastasis were identified, and these cSCCs were matched to primary cSCCs of controls without metastasis (1:1 ratio). The model was developed on the Dutch cohort (n = 390) using a weighted Cox regression model with backward selection and validated on the English cohort (n = 696). Model performance was assessed using weighted versions of the C-index, calibration metrics, and decision curve analysis; and compared to the Brigham and Women's Hospital (BWH) and the American Joint Committee on Cancer (AJCC) staging systems. Members of the multidisciplinary Skin Cancer Outcomes (SCOUT) consortium were surveyed to interpret metastatic risk cutoffs in a clinical context., Findings: Eight out of eleven clinico-pathological variables were selected. The model showed good discriminative ability, with an optimism-corrected C-index of 0.80 (95% Confidence interval (CI) 0.75-0.85) in the development cohort and a C-index of 0.84 (95% CI 0.81-0.87) in the validation cohort. Model predictions were well-calibrated: the calibration slope was 0.96 (95% CI 0.76-1.16) in the validation cohort. Decision curve analysis showed improved net benefit compared to current staging systems, particularly for thresholds relevant for decisions on follow-up and adjuvant treatment. The model is available as an online web-based calculator (https://emc-dermatology.shinyapps.io/cscc-abs-met-risk/)., Interpretation: This validated model assigns personalised metastatic risk predictions to patients with cSCC, using routinely reported histological and patient-specific risk factors. The model can empower clinicians and healthcare systems in identifying patients with high-risk cSCC and offering personalised care/treatment and follow-up. Use of the model for clinical decision-making in different patient populations must be further investigated., Funding: PPP Allowance made available by Health-Holland, Top Sector Life Sciences & Health, to stimulate public-private partnerships., Competing Interests: MW participated as speaker/advisory board member/consultant for Sanofi Genzyme, Sunpharma and LEO Pharma. DB is employed by SkylineDx. BRP was employed by SkylineDx before beginning the submitted work (December 2019–July 2021). All other authors declare no competing interests., (© 2023 The Author(s).)

Background: Lymphocyte skin homing in atopic eczema (AE) may induce lymphopenia., Objective: To determine if AE is associated with lymphopenia., Methods: We used UK primary care electronic health records (Clinical Practice Research Datalink GOLD) for a matched cohort study in adults (18 years+) (1997-2015) with at least one recorded lymphocyte count. We matched people with AE to up to five people without. We used multivariable logistic regression to estimate the association between AE and lymphopenia (two low lymphocyte counts within 3 months) and linear mixed effects regression to estimate the association with absolute lymphocyte counts using all available counts. Cox proportional hazard models were used to investigate the effect of lymphopenia on common infections. We replicated the study using US survey data (National Health and Nutrition Examination Survey [NHANES])., Results: Among 71,731 adults with AE and 126,349 adults without AE, we found an adjusted odds ratio (OR) for lymphopenia of 1.16 (95% CI: 1.09-1.23); the strength of association increased with increasing eczema severity. When comparing all recorded lymphocyte counts from adults with AE (n = 1,497,306) to those of people without AE (n = 4,035,870) we saw a lower mean lymphocyte (adjusted mean difference -0.047 × 10 9 /L [95% CI: -0.051 to -0.043]) in those with AE. The difference was larger for men, with increasing age, and with increasing AE severity and was present among people with AE not treated with immunosuppressive drugs. In NHANES (n = 22,624), the adjusted OR for lymphopenia in adults with AE was 1.30 (95% CI: 0.80-2.11), and the adjusted mean lymphocyte count difference was -0.03 × 10 9 /L (95% CI: -0.07 to 0.02). Despite having a lower lymphocyte count, adjusting for time with lymphopenia, did not alter risk estimates of infections., Conclusion: Atopic eczema, including increasing AE severity, is associated with a decreased lymphocyte count, regardless of immunosuppressive drug use. Whether the lower lymphocyte count has wider health implications for people with severe eczema warrants further investigation., (© 2023 The Authors. Journal of the European Academy of Dermatology and Venereology published by John Wiley & Sons Ltd on behalf of European Academy of Dermatology and Venereology.)

Background: The COVID-19 pandemic reduced the number of skin cancer diagnoses, potentially causing a progression to unfavourable tumour stages., Objectives: To identify the impact of delayed diagnostics on primary invasive melanoma and cutaneous squamous cell carcinoma (cSCC) by comparing tumour (pT) stage, Breslow thickness and invasion depth from before to after the first and second lockdown periods., Methods: In this population-based cohort study, histopathology reports registered between 1 January 2018 and 22 July 2021 were obtained from the nationwide histopathology registry in the Netherlands. The Breslow thickness of melanomas, invasion depth of cSCCs, and pT stage for both tumour types were compared across five time periods: (i) pre-COVID, (ii) first lockdown, (iii) between first and second lockdowns, (iv) second lockdown and (v) after second lockdown. Breslow thickness was compared using an independent t-test. pT-stage groups were compared using a χ 2 -test. Outcomes were corrected for multiple testing using the false discovery rate., Results: In total, 20 434 primary invasive melanomas and 68 832 cSCCs were included in this study. The mean primary melanoma Breslow thickness of the prepandemic era (period i) and the following time periods (ii-v) showed no significant difference. A small shift was found towards unfavourable pT stages during the first lockdown compared with the pre-COVID period: pT1 52·3% vs. 58·6%, pT2 18·9% vs. 17·8%, pT3 13·2% vs. 11·0%, pT4 9·1% vs. 7·3% (P = 0·001). No relevant changes were seen in subsequent periods. No significant change in pT stage distribution was observed between the pre-COVID (i) and COVID-affected periods (ii-v) for cSCCs., Conclusions: To date, the diagnostic delay caused by COVID-19 has not resulted in relatively more unfavourable primary tumour characteristics of melanoma or cSCC. Follow-up studies in the coming years are needed to identify a potential impact on staging distribution and survival in the long term., (© 2022 The Authors. British Journal of Dermatology published by John Wiley & Sons Ltd on behalf of British Association of Dermatologists.)

Background: Risk factors for cutaneous squamous cell carcinoma (cSCC) metastasis have been investigated only in relatively small data sets., Objective: To analyze and replicate risk factors for metastatic cSCC., Methods: From English and Dutch nationwide cancer registry cohorts, metastatic cases were selected and 1:1 matched to controls. The variables were extracted from pathology reports from the National Disease Registration Service in England. In the Netherlands, histopathologic slides from the Dutch Pathology Registry were revised by a dermatopathologist. Model building was performed in the English data set using backward conditional logistic regression, whereas replication was performed using the Dutch data set., Results: In addition to diameter and thickness, the following variables were significant risk factors for metastatic cSCC in the English data set (n = 1774): poor differentiation (odds ratio [OR], 4.56; 95% CI, 2.99-6.94), invasion in (OR, 1.69; 95% CI, 1.05-2.71)/beyond (OR, 4.43; 95% CI, 1.98-9.90) subcutaneous fat, male sex (OR, 2.59; 95% CI, 1.70-3.96), perineural/lymphovascular invasion (OR, 2.12; 95% CI, 1.21-3.71), and facial localization (OR, 1.57; 95% CI, 1.02-2.41). Diameter and thickness showed significant nonlinear relationships with metastasis. Similar ORs were observed in the Dutch data set (n = 434 cSCCs)., Limitations: Retrospective use of pathology reports in the English data set., Conclusion: cSCC staging systems can be improved by including differentiation, clinical characteristics such as sex and tumor location, and nonlinear relationships for diameter and thickness., Competing Interests: Conflicts of interest Dr Wakkee participated as an advisory board member on advanced cutaneous squamous cell carcinoma for Sanofi Genzyme for which she received a financial reimbursement. Authors Tokez, Qi, and Rentroia-Pacheco and Drs Venables, Hollestein, Bramer, van den Bos, Rous, Leigh, Nijsten, and Mooyaart have no conflicts of interest to declare., (Copyright © 2022 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.)

Background: The current standard of care for patients without sentinel node (SN) metastasis (i.e., stage I−II melanoma) is watchful waiting, while >40% of patients with stage IB−IIC will eventually present with disease recurrence or die as a result of melanoma. With the prospect of adjuvant therapeutic options for patients with a negative SN, we assessed the performance of a clinicopathologic and gene expression (CP-GEP) model, a model originally developed to predict SN metastasis, to identify patients with stage I−II melanoma at risk of disease relapse. Methods: This study included patients with cutaneous melanoma ≥18 years of age with a negative SN between October 2006 and December 2017 at the Sahlgrenska University Hospital (Sweden) and Erasmus MC Cancer Institute (The Netherlands). According to the CP-GEP model, which can be applied to the primary melanoma tissue, the patients were stratified into high or low risk of recurrence. The primary aim was to assess the 5-year recurrence-free survival (RFS) of low- and high-risk CP-GEP. A secondary aim was to compare the CP-GEP model with the EORTC nomogram, a model based on clinicopathological variables only. Results: In total, 535 patients (stage I−II) were included. CP-GEP stratification among these patients resulted in a 5-year RFS of 92.9% (95% confidence interval (CI): 86.4−96.4) in CP-GEP low-risk patients (n = 122) versus 80.7% (95%CI: 76.3−84.3) in CP-GEP high-risk patients (n = 413; hazard ratio 2.93 (95%CI: 1.41−6.09), p < 0.004). According to the EORTC nomogram, 25% of the patients were classified as having a ‘low risk’ of recurrence (96.8% 5-year RFS (95%CI 91.6−98.8), n = 130), 49% as ‘intermediate risk’ (88.4% 5-year RFS (95%CI 83.6−91.8), n = 261), and 26% as ‘high risk’ (61.1% 5-year RFS (95%CI 51.9−69.1), n = 137). Conclusion: In these two independent European cohorts, the CP-GEP model was able to stratify patients with stage I−II melanoma into two groups differentiated by RFS.

Background: Cutaneous squamous cell carcinoma (cSCC) is the second most common cancer worldwide with relatively low metastatic potential (2-5%). Developments in therapeutic options have highlighted the need to better identify high-risk patients who could benefit from closer surveillance, adjuvant therapies and baseline/follow-up imaging, while at the same time safely omitting low-risk patients from further follow-up. Controversy remains regarding the predictive performance of current cSCC staging systems and which methodology to adopt., Objectives: To validate the performance of four cSCC staging systems [American Joint Committee on Cancer 8th edition (AJCC8), Brigham and Women's Hospital (BWH), Tübingen and Salamanca T3 refinement] in predicting metastasis using a nationwide cohort., Methods: A nested case-control study using data from the National Disease Registration Service, England, 2013-2015 was conducted. Metastatic cSCC cases were identified using an algorithm to identify all potential cases for manual review. These were 1 : 1 matched on follow-up time to nonmetastatic controls randomly selected from 2013. Staging systems were analysed for distinctiveness, homogeneity, monotonicity, specificity, positive predictive value (PPV), negative predictive value (NPV) and c-index., Results: We included 887 metastatic cSCC cases and 887 nonmetastatic cSCC controls. The BWH system showed the highest specificity [92.8%, 95% confidence interval (CI) 90.8-94.3%, PPV (13.2%, 95% CI 10.6-16.2) and c-index (0.84, 95% CI 0.82-0.86). The AJCC8 showed superior NPV (99.2%, 95% CI 99.2-99.3), homogeneity and monotonicity compared with the BWH and Tübingen diameter and thickness classifications (P < 0.001). Salamanca refinement did not show any improvement in AJCC8 T3 cSCC staging., Conclusions: We validated four cSCC staging systems using the largest nationwide dataset of metastatic cSCC so far. Although the BWH system showed the highest overall discriminative ability, PPV was low for all staging systems, which shows the need for further improvement and refining of current cSCC staging systems., (© 2021 The Authors. British Journal of Dermatology published by John Wiley & Sons Ltd on behalf of British Association of Dermatologists.)

The Environmental Effects Assessment Panel of the Montreal Protocol under the United Nations Environment Programme evaluates effects on the environment and human health that arise from changes in the stratospheric ozone layer and concomitant variations in ultraviolet (UV) radiation at the Earth's surface. The current update is based on scientific advances that have accumulated since our last assessment (Photochem and Photobiol Sci 20(1):1-67, 2021). We also discuss how climate change affects stratospheric ozone depletion and ultraviolet radiation, and how stratospheric ozone depletion affects climate change. The resulting interlinking effects of stratospheric ozone depletion, UV radiation, and climate change are assessed in terms of air quality, carbon sinks, ecosystems, human health, and natural and synthetic materials. We further highlight potential impacts on the biosphere from extreme climate events that are occurring with increasing frequency as a consequence of climate change. These and other interactive effects are examined with respect to the benefits that the Montreal Protocol and its Amendments are providing to life on Earth by controlling the production of various substances that contribute to both stratospheric ozone depletion and climate change., (© 2022. The Author(s).)

Background: Cutaneous squamous cell carcinoma (cSCC) represents the most serious form of keratinocyte cancers because of its metastatic potential. Studies on nationwide incidence and disease-specific survival rates of metastatic cSCC (mcSCC) are lacking., Objective: To investigate the cumulative incidence and disease-specific survival of patients with mcSCC in the Dutch population and assess patient-based risk factors., Methods: We conducted a nationwide cancer registry study including all patients with the first cSCC in 2007 or 2008, using data from the Netherlands Cancer Registry, the nationwide network and registry of histopathology and cytopathology, and Statistics Netherlands. Cumulative incidence and Kaplan-Meier curves were calculated, and time-dependent Cox proportional hazards regression analyses were used., Results: Of the 11,137 patients, metastases developed in 1.9% (n = 217). The median time to metastasis was 1.5 years (interquartile range 0.6-3.8 years). The risk factors were age (adjusted hazard ratio [aHR] 1.03, 95% CI 1.02-1.05), male sex (aHR 1.7, 95% CI 1.3-2.3), and immunosuppression (aHR [organ transplant recipient] 5.0, 95% CI 2.5-10.0; aHR [hematologic malignancy] 2.7, 95% CI 1.6-4.6). The 5-year disease-specific survival for patients with mcSCC was 79.1%., Limitations: Only histopathologically confirmed mcSCCs were included., Conclusion: About 2% of cSCCs metastasize, with higher risk for men, increasing age, and immunocompromised patients. Disease-specific survival for patients with mcSCC is high., Competing Interests: Conflict of interest Dr Wakkee participated as an advisory board member on advanced cSCC for Sanofi Genzyme, for which she received a financial reimbursement. Drs Venables, Mooyaart, Louwman, Nijsten, and Hollestein and Authors Tokez and Kan have no conflicts of interest to declare., (Copyright © 2021 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.)

Background: The incidence of keratinocyte carcinomas is high and rapidly growing. Approximately 80% of keratinocyte carcinomas consist of basal cell carcinomas (BCC) with 50% of these being considered as low-risk tumors. Nevertheless, 83% of the low-risk BCC patients were found to receive more follow-up care than recommended according to the Dutch BCC guideline, which is one visit post-treatment for this group. More efficient management could reduce unnecessary follow-up care and related costs., Objectives: To study the efficacy, cost-utility, and budget impact of a personalized discharge letter for low-risk BCC patients compared with usual care (no personalized letter)., Methods: In a multi-center intervention study, a personalized discharge letter in addition to usual care was compared to usual care in first-time BCC patients. Model-based cost-utility and budget impact analyses were conducted, using individual patient data gathered via surveys. The outcome measures were number of follow-up visits, costs and quality adjusted life years (QALY) per patient., Results: A total of 473 first-time BCC patients were recruited. The personalized discharge letter decreased the number of follow-up visits by 14.8% in the first year. The incremental costs after five years were -€24.45 per patient. The QALYs were 4.12 after five years and very similar in both groups. The national budget impact was -€2,7 million after five years., Conclusions: The distribution of a personalized discharge letter decreases the number of unnecessary follow-up visits and implementing the intervention in a large eligible population would results in substantial cost savings, contributing to restraining the growing BCC costs., Competing Interests: The authors have declared that no competing interests exist.

Background: The Clinicopathological and Gene Expression Profile (CP-GEP) model was developed to accurately identify patients with T1-T3 primary cutaneous melanoma at low risk for nodal metastasis., Objectives: To validate the CP-GEP model in an independent Dutch cohort of patients with melanoma., Methods: Patients (aged ≥ 18 years) with primary cutaneous melanoma who underwent sentinel lymph node biopsy (SLNB) between 2007 and 2017 at the Erasmus Medical Centre Cancer Institute were eligible. The CP-GEP model combines clinicopathological features (age and Breslow thickness) with the expression of eight target genes involved in melanoma metastasis (ITGB3, PLAT, SERPINE2, GDF15, TGFBR1, LOXL4, CXCL8 and MLANA). Using the pathology result of SLNB as the gold standard, performance measures of the CP-GEP model were calculated, resulting in CP-GEP high risk or low risk for nodal metastasis., Results: In total, 210 patients were included in the study. Most patients presented with T2 (n = 94, 45%) or T3 (n = 70, 33%) melanoma. Of all patients, 27% (n = 56) had a positive SLNB, with nodal metastasis in 0%, 30%, 54% and 16% of patients with T1, T2, T3 and T4 melanoma, respectively. Overall, the CP-GEP model had a negative predictive value (NPV) of 90·5% [95% confidence interval (CI) 77·9-96.2], with an NPV of 100% (95% CI 72·2-100) in T1, 89·3% (95% CI 72·8-96·3) in T2 and 75·0% (95% CI 30·1-95·4) in T3 melanomas. The CP-GEP indicated high risk in all T4 melanomas., Conclusions: The CP-GEP model is a noninvasive and validated tool that accurately identified patients with primary cutaneous melanoma at low risk for nodal metastasis. In this validation cohort, the CP-GEP model has shown the potential to reduce SLNB procedures in patients with melanoma., (© 2020 The Authors. British Journal of Dermatology published by John Wiley & Sons Ltd on behalf of British Association of Dermatologists.)

Background: Quality indicators are used to benchmark and subsequently improve quality of healthcare. However, defining good quality indicators and applying them to high-volume care such as skin cancer is not always feasible., Objectives: To determine whether claims data could be used to benchmark high-volume skin cancer care and to assess clinical practice variation., Methods: All skin cancer care-related claims in dermatology in 2016 were extracted from a nationwide claims database (Vektis) in the Netherlands., Results: For over 220,000 patients, a skin cancer diagnosis-related group was reimbursed in 124 healthcare centres. Conventional excision reflected 75% of treatments for skin cancer but showed large variation between practices. Large practice variation was also found for 5-fluorouracil and imiquimod creams. The practice variation of Mohs micrographic surgery and photodynamic therapy was low under the 75th percentile, but outliers at the 100th percentile were detected, which indicates that few centres performed these therapies far more often than average. On average, patients received 1.8 follow-up visits in 2016., Conclusions: Claims data demonstrated large practice variation in treatments and follow-up visits of skin cancer and may be a valid and feasible data set to extract quality indicators. The next step is to investigate whether detected practice variation is unwarranted and if a reduction improves quality and efficiency of care., (© 2021 The Author(s) Published by S. Karger AG, Basel.)

This assessment by the Environmental Effects Assessment Panel (EEAP) of the United Nations Environment Programme (UNEP) provides the latest scientific update since our most recent comprehensive assessment (Photochemical and Photobiological Sciences, 2019, 18, 595-828). The interactive effects between the stratospheric ozone layer, solar ultraviolet (UV) radiation, and climate change are presented within the framework of the Montreal Protocol and the United Nations Sustainable Development Goals. We address how these global environmental changes affect the atmosphere and air quality; human health; terrestrial and aquatic ecosystems; biogeochemical cycles; and materials used in outdoor construction, solar energy technologies, and fabrics. In many cases, there is a growing influence from changes in seasonality and extreme events due to climate change. Additionally, we assess the transmission and environmental effects of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which is responsible for the COVID-19 pandemic, in the context of linkages with solar UV radiation and the Montreal Protocol.

Competing Interests: None declared.

This assessment, by the United Nations Environment Programme (UNEP) Environmental Effects Assessment Panel (EEAP), one of three Panels informing the Parties to the Montreal Protocol, provides an update, since our previous extensive assessment (Photochem. Photobiol. Sci., 2019, 18, 595-828), of recent findings of current and projected interactive environmental effects of ultraviolet (UV) radiation, stratospheric ozone, and climate change. These effects include those on human health, air quality, terrestrial and aquatic ecosystems, biogeochemical cycles, and materials used in construction and other services. The present update evaluates further evidence of the consequences of human activity on climate change that are altering the exposure of organisms and ecosystems to UV radiation. This in turn reveals the interactive effects of many climate change factors with UV radiation that have implications for the atmosphere, feedbacks, contaminant fate and transport, organismal responses, and many outdoor materials including plastics, wood, and fabrics. The universal ratification of the Montreal Protocol, signed by 197 countries, has led to the regulation and phase-out of chemicals that deplete the stratospheric ozone layer. Although this treaty has had unprecedented success in protecting the ozone layer, and hence all life on Earth from damaging UV radiation, it is also making a substantial contribution to reducing climate warming because many of the chemicals under this treaty are greenhouse gases.

Background: Keratinocyte carcinomas (KC) impact patient quality of life (QoL). There is a need for validated QoL instruments specific to KC. The Basal and Squamous Cell Carcinoma QoL (BaSQoL) questionnaire was developed to comprehensively measure issues of importance to patients with KC., Objective: To validate and characterize the BaSQoL questionnaire for QoL measurement after diagnosis and treatment of KC., Methods: This was a prospective, observational study. Patients with basal cell carcinoma (BCC) or squamous cell carcinoma (SCC) were asked to fill out BaSQoL, Skin Cancer Index (SCI), and Hospital Anxiety and Depression Scale (HADS) questionnaires. Descriptive statistics and classical test theory were used to assess validity., Results: One hundred eighty-seven subjects enrolled in this study: 122 with BCC and 65 with SCC. One hundred seventy-one subjects (91.4%) completed questionnaires at all 3 time points; 16 patients (8.6%) were lost to follow-up. Overall performance using classical test theory was good, with good internal consistency (Cronbach's α 0.63-0.80). BaSQoL subscales were strongly correlated with subscales of the SCI, demonstrating convergent validity, and weakly correlated with HADS, showing divergent validity., Conclusion: The English language version of BaSQoL has good face, content, and construct validity. This study validates BaSQoL for use in English-speaking patients with BCC and SCC.

Background: Dupilumab is the first biologic registered for the treatment of moderate-to-severe atopic dermatitis (AD), and efficacy was shown in phase III clinical trials (primary outcome at week 16 was reached in 38% of patients). Currently, there are limited daily practice data available for dupilumab, especially when it is combined with systemic immunosuppressants., Objectives: To evaluate dupilumab treatment in daily practice in patients with AD., Methods: In this observational cohort study, we prospectively included all adult patients with AD who had been treated with dupilumab in two university hospitals in the Netherlands. Concomitant systemic immunosuppressive treatment was monitored. Physician-reported outcome measures and patient-reported outcome measures (PROMs) after ≥ 12 weeks of follow-up were analysed. We used a linear mixed-effects model to determine changes in scores during follow-up., Results: Ninety-five patients were included. Of these, 62 patients were using systemic immunosuppressants at baseline; the use of systemic immunosuppressants was continued during dupilumab treatment in 43 patients. From baseline to 16 weeks of treatment, the estimated mean Eczema Area and Severity Index score (0-72) decreased from 18·6 [95% confidence interval (CI) 16·0-21·4)] to 7·3 (95% CI 5·4-10·0), and the estimated mean PROMs showed a decrease of 41-66%. Investigator's Global Assessment 0 or 1 (clear/almost clear) was reached in 38% of the patients. Five patients discontinued dupilumab treatment due to side-effects or ineffectiveness. Eye symptoms and orofacial (nonocular) herpes simplex virus (HSV) reactivation were reported in 62% and 8% of the patients, respectively., Conclusions: Dupilumab treatment in daily practice shows a clinically relevant improvement of physician-reported outcome measures and PROMs, which is in line with efficacy data from clinical trials. Besides frequently reported eye symptoms and orofacial (nonocular) HSV reactivation, there were no apparent safety concerns. What's already known about this topic? Dupilumab has been shown to be an efficacious treatment for atopic dermatitis in several clinical trials. However, it is known that there may be considerable differences in patient characteristics and treatment responses between clinical trials and daily practice. What does this study add? This study presents the first experience with dupilumab treatment in 95 patients with atopic dermatitis in daily practice in two Dutch university hospitals. Less stringent inclusion and exclusion criteria and follow-up schedules, in contrast to those used in clinical trials, might better represent daily practice. Dupilumab treatment shows a clinically relevant improvement of physician- and patient-reported outcome measures; besides patient-reported eye symptoms (in 59 of 95 patients; 62%) and an apparent increase in orofacial (nonocular) herpes simplex virus reactivation (eight of 95 patients; 8%), there were no other safety concerns during follow-up up to 16 weeks of dupilumab treatment., (© 2019 The Authors. British Journal of Dermatology published by John Wiley & Sons Ltd on behalf of British Association of Dermatologists.)

Background: Older people have the highest incidence of melanoma and the population in most Western countries is ageing. We evaluated how the gap in incidence and survival between younger and older patients has developed during the past decades. Material and methods: All patients diagnosed with cutaneous melanoma between 1989 and 2015 ( n  = 84,827) were identified from the Netherlands Cancer Registry. Elderly were defined as aged ≥70 years. Differences in patient and tumor characteristics were described, age-specific incidence rates were calculated, and relative survival (RS) and multivariable analyses estimating the Relative Excess Rate of dying (RER) were conducted Results: In older men, the melanoma age-standardized incidence increased from 18 to 103/100,000 person-years (py) between 1989 and 2015 and in older women from 23 to 70/100,000 py. In younger men and women, it increased from 8 to 21 and from 13 to 28/100,000 py, respectively. Median Breslow thickness declined from 1.8 to 1.1 mm and from 1.6 to 1.1 mm in older men and women (2003 versus 2015), and from 1.1 to 0.9 mm and 0.9 to 0.8 mm in younger men and women. In older men, 5-year RS increased from 67% (95% CI: 63%-72%) in 1989-1997 to 85% (95% CI: 83%-87%) in 2007-2015 and in older women from 81% (95% CI: 78%-85%) to 89% (95% CI: 87%-91%). In younger men and women, RS increased from 82% (95% CI: 81%-83%) to 90% (95% CI: 90%-91%) and from 92% (95% CI: 92%-93%) to 96% (95% CI: 95%-96%). After case-mix correction , older men and women no longer showed an improved survival over time (RER 2010-2015 versus 2003-2009: 0.97; 95% CI: 0.81-1.16 and 0.95; 95% CI: 0.79-1.16). Whereas in younger men and women survival remained improved (RER 0.75; 95% CI: 0.67-0.83 and 0.77; 95%CI: 0.67-0.89). Conclusion: The gap in melanoma incidence between younger and older people is increasing due to a strong increase in incidence in older adults. Disparities in survival are declining, related to a narrowing gap in Breslow thickness.

Dermatofibrosarcoma protuberans is a rare soft tissue tumour with a very low (p < 0.5%) rate of metastasis. Rates of re-excision and recurrence were determined using data from the Netherlands Cancer Registry between 1989 and 2016. Of the 1,890 instances of dermatofibrosarcoma protuberans included, 87% were treated with excision, 4% with Mohs micrographic surgery, and 9% otherwise or unknown. Linked pathology data were retrieved for 1,677 patients. Half of all excisions (847/1,644) were incomplete and 29% (192/622) of all re-excisions were incomplete. The cumulative incidence of a recurrence was 7% (95% confidence interval (95% CI) 6-8) during a median follow-up of 11 years (interquartile range (IQR) 6-17). After Mohs micrographic surgery (n = 34), there were no recurrences during a median follow-up of 4 years (IQR 3-6). Due to the high rate of incomplete excisions and recurrences after excision, this study supports the European guideline, which recommends treating dermatofibrosarcoma protuberans with Mohs micrographic surgery in order to decrease the rate of recurrence.

Background: Basal cell carcinoma (BCC) and cutaneous squamous cell carcinoma (cSCC), together known as keratinocyte cancers (KCs), are the commonest cancer in white ethnic populations. Recent improvements to registry data collection in England has allowed more accurate analysis of the epidemiology of BCC and cSCC and for the first time we are able to provide an accurate (representative) tumour burden for KC in the U.K., Objectives: To estimate the incidence of BCC and cSCC in the U.K., Methods: A cohort of patients with KCs between 2013 and 2015 were identified using linkage to diagnostic codes derived from pathology reports collected into the national cancer registry. Data from England's cancer registry were combined with data from Scotland, Northern Ireland and Wales. European age-standardized incidence rates (EASRs) of the first BCC and cSCC per patient per annum (PPPA) were calculated., Results: In the U.K, the EASR of the first BCC and cSCC PPPA in 2013-15 were 285 and 77 per 100 000 person years, respectively (211 120 KCs total in 2015). The mean annual percentage increase was 5% between 2013 and 2015 for both BCC and cSCC. By counting the first KC PPPA, we include an additional 51% KCs compared with the previous reporting technique which counts only the first BCC and cSCC in a patient's lifetime, yet it represents a probable underestimation of 5-11% of the true tumour count., Conclusions: Based on an improved methodology, a more representative incidence of KC is presented, which is essential to healthcare planning and will lead to improved understanding of the epidemiology of KC. What's already known about this topic? Keratinocyte cancers (KCs) are the most common cancers affecting white ethnic populations. The incidence of basal cell carcinoma (BCC) and cutaneous squamous cell carcinoma (cSCC) is increasing worldwide including the U.K., most commonly in elderly male Caucasian patients. These cancers are traditionally substantially underreported and frequently excluded from national cancer statistics. What does this study add? Using improved data collection methods in England and validated tumour-reporting techniques, we report the most accurate BCC and cSCC incidence data for the U.K. ever published. Identifying the first BCC and cSCC per patient per annum, the incidence of BCC and cSCC in the U.K. (excluding Wales) was 285 and 77 per 100 000 person years, respectively, between 2013 and 2015, with more than 210 000 KCs in the U.K. in 2015., (© 2019 British Association of Dermatologists.)

Background: The high prevalence of actinic keratosis (AK) requires the optimal use of healthcare resources., Objectives: To gain insight in to the healthcare utilization of people with AK in a population-based cohort, and the management of AK in a primary and secondary care setting., Methods: A retrospective cohort study using three complementary data sources was conducted to describe the use of care, diagnosis, treatment and follow-up of patients with AK in the Netherlands. Data sources consisted of a population-based cohort study (Rotterdam Study), routine general practitioner (GP) records (Integrated Primary Care Information) and nationwide claims data (DRG Information System)., Results: In the population-based cohort (Rotterdam Study), 69% (918 of 1322) of participants diagnosed with AK during a skin-screening visit had no previous AK-related visit in their GP record. This proportion was 50% for participants with extensive AK (i.e. ≥ 10 AKs; n = 270). Cryotherapy was the most used AK treatment by both GPs (78%) and dermatologists (41-56%). Topical agents were the second most used treatment by dermatologists (13-21%) but were rarely applied in primary care (2%). During the first AK-related GP visit, 31% (171 of 554) were referred to a dermatologist, and the likelihood of being referred was comparable between low- and high-risk patients, which is inconsistent with the Dutch general practitioner guidelines for 'suspicious skin lesions' from 2017. Annually, 40 000 new claims representing 13% of all dermatology claims were labelled as cutaneous premalignancy. Extensive follow-up rates (56%) in secondary care were registered, while only 18% received a claim for a subsequent cutaneous malignancy in 5 years., Conclusions: AK management seems to diverge from guidelines in both primary and secondary care. Underutilization of field treatments, inappropriate treatments and high referral rates without proper risk stratification in primary care, combined with extensive follow-up in secondary care result in the inefficient use of healthcare resources and overburdening in secondary care. Efforts directed to better risk differentiation and guideline adherence may prove useful in increasing the efficiency in AK management. What's already known about this topic? The prevalence of actinic keratosis (AK) is high and, in particular, multiple AKs are a strong skin cancer predictor. The high prevalence of AK requires optimal use of healthcare resources. Nevertheless, (population based) AK healthcare utilization and management data are very rare. What does this study add? Although AK-related care already consumes substantial resources, about 70% of the AK population has never received care. Primary care AK management demonstrated underutilization of topical therapies and high referral rates without proper risk stratification, while in secondary care the extensive follow-up schedules were applied. This inefficient use of healthcare resources highlights the need for better harmonization and risk stratification to increase the efficiency of AK care., (© 2019 The Authors. British Journal of Dermatology published by John Wiley & Sons Ltd on behalf of British Association of Dermatologists.)

Objectives: The objective of this systematic review and meta-analysis was to summarise available randomised controlled trials (RCTs) of EVLA efficacy, and to define the differences in success rate of variations in wavelength, administered energy, outcome definition, and follow up period., Methods: A literature search was conducted in Embase, Medline (Ovid-SP), Cochrane Central Database, and Web of Science from inception to November 2017. RCTs with follow up of more than three months were included. The studied outcome was the proportion of patients with EVLA treatment success, defined as absence of reflux or occlusion of the great saphenous vein (GSV). Pooled proportions of anatomical success were compared. Subgroup and meta-regression analysis included wavelengths (short [810, 940, and 980 nm], long [1470, 1500, and 1920 nm]), amount of energy (≤50 J/cm, > 50 J/cm), follow up (≤1 year, > 1 year), outcome definition (occlusion, no reflux), and quality of the studies (low risk of bias, unclear/high risk of bias)., Results: Twenty-eight RCTs, with a total of 2829 GSVs were included. The overall success rate of EVLA was 92% (95% CI 90-94%, I 2  = 68%). In subgroup analysis, no statistically significant differences were found for long or short wavelengths (95% [95% CI 91-97%] vs. 92% [95% CI 89-94%], p = .15), high or low administered energy (93% [95% CI 89-95%] vs. 92% [95% CI 90-94%], p = .99), long or short follow up (89% [95% CI 84-93%] vs. 93% [95% CI 91-95%], p = .13) and outcome definition (occlusion group 94% [95% CI 91-96%] vs. absence of reflux group 91% [95% CI 87-94%], p = .26). Studies with low risk of bias reported a significantly higher success rate than high or unclear risk of bias (93% [95% CI 90-95%] vs. 89% [95% CI 83-93%], p = .04)., Conclusions: The overall success rate of EVLA is high (92%), even with increasing follow up. Commonly used parameters of EVLA (wavelength, administered energy, and outcome definition) have no influence on the treatment success rate., (Copyright © 2018 European Society for Vascular Surgery. Published by Elsevier B.V. All rights reserved.)

Background: Despite the widespread use of Mohs micrographic surgery (MMS) for periocular basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) - together called keratinocyte carcinoma (KC) - follow-up data regarding recurrences are limited., Objectives: To investigate the recurrence rate for periocular KCs after MMS and to describe our experience with interdisciplinary collaborations., Methods: Patients with periocular KCs treated with MMS between 2006 and 2016 in a tertiary MMS referral hospital were included in this retrospective cohort study. Descriptive statistics were used to describe the MMS procedure-related characteristics. Using follow-up data from the electronic patient records and linkage with the Dutch nationwide network and registry of histopathology and cytopathology on 30 June 2017, the recurrence rate was evaluated and calculated using a cumulative incidence curve., Results: In total, 683 (93·7%) periocular BCCs and 46 (6·3%) SCCs were treated with MMS. Three-quarters (n = 549) were primary tumours and the majority were located at the medial canthus or lower eyelid (n = 649, 89·0%). In 505 MMS procedures (69·3%) an oculoplastic surgeon participated, and in 63 patients (8·6%) a plastic surgeon performed the reconstruction. After a median follow-up of 46 months the recurrence rate was 3·0%, based on 22 recurrences (20 BCCs and two SCCs)., Conclusions: MMS is an excellent treatment option for periocular KCs, with a low recurrence rate. Due to this specific anatomical location an interdisciplinary approach should pre-eminently be considered., (© 2018 The Authors. British Journal of Dermatology published by John Wiley & Sons Ltd on behalf of British Association of Dermatologists.)

Sample size and power calculations help determine if a study is feasible based on a priori assumptions about the study results and available resources. Trade-offs must be made between the probability of observing the true effect and the probability of type I errors (α, false positive) and type II errors (β, false negative). Calculations require specification of the null hypothesis, the alternative hypothesis, type of outcome measure and statistical test, α level, β, effect size, and variability (if applicable). Because the choice of these parameters may be quite arbitrary in some cases, one approach is to calculate the sample size or power over a range of plausible parameters before selecting the final sample size or power. Considerations that should be taken into account could include correction for nonadherence of the participants, adjustment for multiple comparisons, or innovative study designs., (Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Melanoma is rare in the first two decades of life. Trends in incidence differ across countries., Objective: To describe incidence and relative survival of children and adolescents with melanoma in the Netherlands for children (0 through 11 years) and adolescents (12 through 19 years) separately. We hypothesized that adolescent melanoma increased in contrast to childhood melanoma, possibly due to a difference in cancer biology and sun exposure patterns., Methods: Data on all patients of 0-19 years diagnosed between 1989 and 2013 with histologically confirmed cutaneous invasive melanoma were retrieved from the Netherlands Cancer Registry (NCR). Incidence trends were analysed with Joinpoint regression. Relative survival analysis was performed., Results: Between 1989 and 2013, 80 children and 544 adolescents with melanoma were registered in the NCR. Median age at diagnosis was 17 years (IQR 15-18); the female-to-male ratio was 1.7 : 1 Statistically significant incidence trends were found in the older age group (12-19 years): an increasing incidence since 1991 [annual percentage change (APC) 3.2%, 95%CI 1.3-5.1] followed by a decrease from 2005 to 2013 (APC -4.9%, 95%CI -9.6-0.0). No incidence trends for childhood melanoma were observed (APC 0.3%, 95% CI -3.0-3.8). Relative survival at 1, 5 and 10 years was 98% (95% CI 97-99), 94% (95% CI 92-96) and 90% (95% CI 87-92), respectively. Survival was worse in males and higher Breslow thickness., Conclusions: Melanoma is very rare under the age of 12 with stable incidence rates. In comparison with childhood melanoma, melanomas in adolescents are more common with a decreasing trend in the past decade. Male sex and increasing Breslow thickness are associated with worse survival in paediatric melanoma patients., (© 2017 European Academy of Dermatology and Venereology.)

Background: Skin cancer patients are primarily at increased risk of developing subsequent skin cancers of the same type. Shared risk factors might also increase the occurrence of a different type of subsequent skin cancer., Objective: To investigate risks of different skin tumour combinations after a first melanoma, squamous cell carcinoma (SCC) and basal cell carcinoma (BCC)., Methods: All melanoma and SCC patients included in the national Netherlands Cancer Registry (NCR) and all BCC patients included in the regional Eindhoven Cancer Registry (ECR) between 1989 and 2009 were followed until diagnosis of a subsequent different skin cancer (melanoma, SCC or BCC), date of death or end of study. Cumulative risks, standardized incidence ratios (SIR) and absolute excess risks (AER) of subsequent skin cancers were calculated., Results: A total of 50 510 melanoma patients and 64 054 patients with a SCC of the skin were included (national data NCR). The regional data of the ECR consisted of 5776 melanoma patients, 5749 SCC patients and 41 485 BCC patients. The 21-year cumulative risk for a subsequent melanoma after a first SCC or BCC was respectively 1.7% and 1.3% for males and 1.3% and 1.2% for females; SCC after melanoma or BCC was 4.6% and 9.3% (males) and 2.6% and 4.1% (females); BCC after melanoma or SCC was respectively 13.2% and 27.8% (males) and 14.9% and 21.1% (females). SIRs and AERs remained elevated up to 21 years after the first melanoma, SCC or BCC., Conclusion: This large population-based study investigating risks of developing a different subsequent cutaneous malignancy showed high-cumulative risks of mainly KC and markedly increased relative and absolute risks of all tumour combinations. These estimates confirm a common carcinogenesis and can serve as a base for follow-up guidelines and patient education aiming for an early detection of the subsequent cancers., (© 2017 European Academy of Dermatology and Venereology.)

Health-related quality of life (HRQoL) is important in the management of basal cell carcinoma (BCC) and squamous cell carcinoma (SCC). Disease-specific questionnaires exist, but with important shortcomings. The aim of this study was to develop and validate a questionnaire suitable for use in all patients with BCC and those with SCC. In a 4-phase trajectory, a preliminary questionnaire was created and population-based testing (1,173 patients) carried out. The questionnaire was reduced using exploratory factor analysis and item response theory. Individual item performance was assessed using classical test theory. A total of 721 patients completed the questionnaire. The number of items was reduced to 16, covering 5 scales. Confirmatory factor analysis showed a good fit. Cronbach�s ?s (range 0.67�0.82) were reasonable to high with good internal consistency. In conclusion, the Basal and Squamous Cell Carcinoma Quality of Life questionnaire has good face, content and construct validity. It is useful in the wide range of BCC and SCC patients and captures HRQoL impact over different time-frames.

Background: The Actinic Keratosis Quality of Life Questionnaire (AKQoL) is a disease-specific instrument to measure the impact of actinic keratosis (AK) on patients' lives., Objective: To validate and test the psychometric properties of the AKQoL translated into the Dutch language (AKQoL-NL)., Methods: All new patients ≥50 years of age with untreated AK in a university medical center and a general hospital between August 2014 and August 2015 were eligible. The AKQoL was obtained and repeated after 2 weeks. The feasibility was tested by missing responses and response distribution. The internal consistency reliability of each domain was investigated with the Cronbach alpha, and test-retest reliability and validity with the Spearman correlation coefficient. AKQoL scores were compared to the Skindex-17 for convergent validity and to the Groningen Frailty Indicator scores for divergent validity., Results: A total of 153 of 190 eligible patients consented to participate. Feasibility analysis showed that none of the items missed ≥10% of responses but 5 of the 9 items showed floor effect. The AKQoL subscales showed a moderate internal consistency (Cronbach α = 0.235-0.468) and an excellent test-retest reliability (interclass correlation coefficient = 0.997-1). The AKQoL correlated poorly with the symptom component and moderately with the psychosocial component of the Skindex-17 (ρ = -0.015 to 0.346 and 0.324 to 0.501, respectively), which is less than expected. The AKQoL scored poorly in both of the Groningen Frailty Indicator (GFI) components (ρ = -0.97 to 0.12 and 0.185 to 0.276, respectively), as expected., Conclusion: The AKQoL-NL is a feasible, moderately valid, and moderately reliable health-related quality of life questionnaire., (© 2018 The Author(s) Published by S. Karger AG, Basel.)

The first European Dermato-Epidemiology Network (EDEN) forum was held on 30-31 March 2017 in Madrid, Spain. Dermatoepidemiology describes the study of causes, prevention, health services research and evaluation of interventions of skin diseases. EDEN aims to promote high-quality research, share expertise and facilitate collaboration. These aims were achieved during the EDEN forum by including a preconference course on skin cancer epidemiology; having excellent world-leading guest speakers on causality, quality of care, pharmacoepidemiology and missing data analysis; and including delegates who presented and discussed innovative research findings. The meeting brought together delegates from 11 different countries. We welcome everyone with an interest in clinical research and epidemiology related to skin disease to attend next year's meeting in March 2018 in Berlin., (© 2017 British Association of Dermatologists.)

Facial wrinkling is one of the most notable signs of skin aging. Men and women show different wrinkling patterns yet the lifestyle and physiological factors underlying these sex-specific patterns are relatively unknown. Here, we investigated sex-specific determinants for facial wrinkles. Wrinkle area was quantified digitally using facial photographs of 3,831 northwestern Europeans (51-98 years, 58% female). Effect estimates from multivariable linear regressions are presented as the percentage difference in the mean value of wrinkle area per unit increase of a determinant (%Δ). Wrinkle area was higher in men (median 4.5%, interquartile range: 2.9-6.3) than in women (3.6%, interquartile range: 2.2-5.6). Age was the strongest determinant, and current smoking (men: 15.5%Δ; women: 30.9%Δ) and lower body mass index (men: 1.7%Δ; women: 1.8%Δ) were also statistically significantly associated with increased wrinkling. Pale skin color showed a protective effect (men: -21.0%Δ; women: -28.5%Δ) and, in men, sunburn tendency was associated with less wrinkling. In women, low educational levels and alcohol use were associated with more wrinkling, whereas female pattern hair loss and a higher free androgen index were associated with less wrinkling. In summary, we validated known and identified additional determinants for wrinkling. Skin aging-reducing strategies should incorporate the sex differences found in this study., (Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Medication use in patients with psoriasis has been studied mostly in the context of psoriasis comorbidities., Objectives: To investigate detailed drug utilization in patients with psoriasis compared with controls in a population-based sample., Methods: This was a case-control study based on drug prescriptions derived from a Dutch general practitioner database where patients with psoriasis and controls without psoriasis were matched 1 : 1 for age, sex, general practitioner and duration of follow-up, between 2002 and 2012. We calculated Mantel-Haenszel odds ratios (ORs) and 95% confidence intervals (CIs) for all therapeutic groups and chemical substances., Results: In total 17 627 patients with psoriasis and 17 627 controls were followed for > 4 years. Overall 20% of patients with psoriasis received no psoriasis treatment and 8% had moderate-to-severe disease. During the entire follow-up a mean of nine unique drugs were prescribed in patients with psoriasis; this was significantly higher than in controls (mean of seven). Drug use did not peak around the date of diagnosis for psoriasis, but remained constant over time. All of the most commonly prescribed therapeutic groups were significantly more often prescribed in patients with psoriasis than in controls. These included drugs associated with psoriasis symptoms and treatment (OR 2·17, 95% CI 2·07-2·28 and OR 22, 95% CI 21-25, respectively), drugs related to psoriasis comorbidities (1·46, 95% CI 1·39-1·53) and a proportion of drugs that were a priori not expected to be increased in patients with psoriasis, such as nasal preparations and laxatives., Conclusions: Patients with psoriasis received more prescriptions for all drugs, regardless of associated comorbidities. This overall increased use of drugs suggests an increased healthcare utilization in patients with psoriasis identified in routine databases., (© 2016 British Association of Dermatologists.)