Long-Term Use of Nonsteroidal Anti-inflammatory Drugs Decreases the Risk of Cutaneous Melanoma: Results of a United States Case–Control Study

Experimental and observational studies continue to demonstrate conflicting results regarding the role of several commonly used drugs as melanoma chemopreventive agents. This case–control study was designed to assess the associations between cutaneous melanoma (CM) and exposure to nonsteroidal anti-inflammatory drugs (NSAIDs) and statins in current users. A total of 400 CM and 600 eligible age- and gender-matched community-based controls were prospectively recruited and interviewed. We assessed participants’ demographic characteristics, CM risk factors, and current and previous use of medications. Multivariable conditional logistic regression models were used to estimate adjusted odds ratios (ORs) and 95% confidence intervals (CIs) for associations between NSAIDs and/or aspirin (ASA), statin exposure, and CM risk. Half of the subjects were men (mean age 60 years). After adjusting for confounders, use of any type of NSAIDs for more than 5 years significantly reduced the risk of melanoma development compared with the low-exposure group (adjusted OR=0.57; 95% CI=0.43–0.77). Subgroup analyses showed that the observed risk reduction was primarily driven by continuous ASA use (>5 years adjusted OR=0.51, 95% CI=0.35–0.75). No significant protective effect was observed with statin exposure (OR=0.97, 95% CI=0.73–1.29). Long-term use of NSAIDs, especially ASA, is associated with a significantly decreased risk of CM development. Clinical intervention studies are warranted to further investigate the potential role of ASA and other NSAIDs as chemopreventive agents for CM.JID JOURNAL CLUB ARTICLE: For questions, answers, and open discussion about this article, please go to http://www.nature.com/jid/journalclu

Statin use and its effect on all-cause mortality of melanoma patients:A population-based Dutch cohort study

Preclinical data showed anticancer effects of statins in melanoma, but meta-analyses could not demonstrate a reduced melanoma incidence in statin users. Rather than preventing occurrence, statins might reduce growth and metastatic spread of melanomas and ultimately improve survival. In this population-based study, we investigated the relationship between statin use and survival of melanoma patients. Patients ≥18 years who were diagnosed with cutaneous melanoma (Breslow thickness >1 mm) and registered in the Eindhoven Cancer Registry and in PHARMO Database Network between 1 January 1998 and 31 December 2010 were eligible. The hazard ratio (HR) of all-cause mortality was calculated by employing adjusted time-dependent and time-fixed Cox proportional hazard models. Disease-specific survival was estimated by means of 3-year relative survival rates (RSR). A control cohort of randomly selected patients using statins from PHARMO Database Network matched on age and gender was used to compare RSR of statin users to the general population. After melanoma diagnosis, 171 of 709 patients used statins. Use of statins showed a nonsignificantly decreased hazard of death (adjusted HR 0.76, 95% confidence interval [CI] 0.50–1.61). After stratification for gender, male but not female statin users showed a favorable outcome compared to nonusers (HR 0.57, 95% CI 0.32–0.99; HR 1.22, 95% CI 0.62–2.38, respectively). Three-year RSR for male statin users tended to be higher than for nonusers (91% vs. 80.5%, P = 0.06), no differences were observed in women (87.1% vs. 92.5%, P = 0.76). Statin use was not associated with an improved survival of melanoma patients. The trend for better survival of male in contrast to female statin users warrants further research

Epidemiology of basal and cutaneous squamous cell carcinoma in the U.K. 2013–15:a cohort study

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

Non-vacuum Solutions of Bianchi Type VI_0 Universe in f(R) Gravity

In this paper, we solve the field equations in metric f(R) gravity for Bianchi type VI_0 spacetime and discuss evolution of the expanding universe. We find two types of non-vacuum solutions by taking isotropic and anisotropic fluids as the source of matter and dark energy. The physical behavior of these solutions is analyzed and compared in the future evolution with the help of some physical and geometrical parameters. It is concluded that in the presence of isotropic fluid, the model has singularity at $\tilde{t}=0$ and represents continuously expanding shearing universe currently entering into phantom phase. In anisotropic fluid, the model has no initial singularity and exhibits the uniform accelerating expansion. However, the spacetime does not achieve isotropy as $t\rightarrow\infty$ in both of these solutions.Comment: 20 pages, 5 figures, accepted for publication in Astrophys. Space Sc

Increasing Costs of Skin Cancer due to Increasing Incidence and Introduction of Pharmaceuticals, 2007-2017

Skin cancer is the most common type of cancer and its incidence is increasing. The objective of this study was to describe the trends in reimbursed drug and hospital costs of benign and (pre)malignant skin tumours, and to present future projections. Therefore, nationwide hospital and drug reimbursement data (for the period 2007–17) were used. In 2017, malignant skin tumours were the 4(th) most costly cancer in the Netherlands (after breast, colorectal, and lung cancer). The total costs for skin tumours increased from €278 million for 384,390 patients (in 2007) to €465 million for 578,355 patients (in 2017). Drug costs increased from €0.7 million to €121 million (over the period 2007–17), resulting in a 26% share of overall costs in 2017. Future costs are projected to reach €1.35 billion in 2030. In conclusion, the increasing costs of skin cancer are strongly affected by the increasing incidence and introduction of expensive drugs, and future projections are for an alarming increase

Effectiveness of dupilumab treatment in 95 patients with atopic dermatitis: daily practice data

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 we

S-100B as an extra selection tool for FDG PET/CT scanning in follow-up of AJCC stage III melanoma patients

Background and Objectives This current study assessed the value of S-100B measurement to guide fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) scanning for detecting recurrent disease in stage III melanoma patients. Methods This study included 100 stage III melanoma patients in follow-up after curative lymph node dissection. Follow-up visits included physical examination and S-100B monitoring. FDG PET/CT scanning was indicated by clinical symptoms and/or elevated S-100B. Results Of 100 patients, 13 (13%) had elevated S-100B without clinical symptoms, of whom 7 (54%) showed disease evidence upon FDG PET/CT scanning. Twenty-six patients (26%) had clinical symptoms with normal S-100B and FDG PET/CT revealed metastasis in 20 (77%). Three patients had clinical symptoms and elevated S-100B, and FDG PET/CT revealed metastasis in all three (100%). Overall, FDG PET/CT scanning revealed metastasis in 30 of the 42 patients (71.4%). For seven recurrences, elevated S-100B prompted early detection of asymptomatic disease; 10% of all asymptomatic patients in follow-up, 23% of all patients with recurrent disease. Conclusion S-100B cannot exclude recurrent disease during follow-up of stage III melanoma. However, adding S-100B measurement to standard clinical assessment can guide FDG PET/CT scanning for detecting recurrent melanoma

Estimating the potential survival gains by eliminating socioeconomic and sex inequalities in stage at diagnosis of melanoma.

BACKGROUND: Although inequalities in cancer survival are thought to reflect inequalities in stage at diagnosis, little evidence exists about the size of potential survival gains from eliminating inequalities in stage at diagnosis. METHODS: We used data on patients diagnosed with malignant melanoma in the East of England (2006-2010) to estimate the number of deaths that could be postponed by completely eliminating socioeconomic and sex differences in stage at diagnosis after fitting a flexible parametric excess mortality model. RESULTS: Stage was a strong predictor of survival. There were pronounced socioeconomic and sex inequalities in the proportion of patients diagnosed at stages III-IV (12 and 8% for least deprived men and women and 25 and 18% for most deprived men and women, respectively). For an annual cohort of 1025 incident cases in the East of England, eliminating sex and deprivation differences in stage at diagnosis would postpone approximately 24 deaths to beyond 5 years from diagnosis. Using appropriate weighting, the equivalent estimate for England would be around 215 deaths, representing 11% of all deaths observed within 5 years from diagnosis in this population. CONCLUSIONS: Reducing socioeconomic and sex inequalities in stage at diagnosis would result in substantial reductions in deaths within 5 years of a melanoma diagnosis.This article is an independent research supported by different funding bodies, beyond the authors’ own employing organisations. MJR was partially funded by a Cancer Research UK Postdoctoral Fellowship (CRUK_A13275). GL is supported by a Postdoctoral Fellowship award by the National Institute for Health Research (NIHR PDF-2011-04-047) to end of 2014 and a Cancer Research UK Clinician Scientist Fellowship award (A18180) from January 2015. The views expressed in this publication are those of the authors and not necessarily those of the National Health Service (NHS), the National Institute for Health Research, the Department of Health, Cancer Research UK, or any other organisation. We thank all staff at the National Cancer Registration Service, Public Health England, Eastern Office, who helped collect and code data used in this study. We particularly acknowledge the help of Dr Clement H Brown and Dr Brian A Rous who were responsible for staging.This is the final published version. It first appeared at http://www.nature.com/bjc/journal/v112/n1s/full/bjc201550a.html

Environmental effects of stratospheric ozone depletion, UV radiation, and interactions with climate change : UNEP Environmental Effects Assessment Panel, Update 2021

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.Peer reviewe