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Clinical utility of intralesional methotrexate to distinguish crateriform keratinocytic tumors before surgeryDear Editors,Keratoacanthoma (KA) and cutaneous squamous cell carci-noma (CSCC) may adopt an identical crateriform morpho-logy. Nowadays, the debate about whether KA is a distinct entity, or a low-grade variant of cutaneous squamous cell carcinoma (CSCC) still persists. Since CSCC is a more ag-gressive neoplasm, misdiagnosing crateriform lesions may have a negative impact on the patient's prognosis. Evaluating a partial biopsy is extremely challenging to confidently dis-tinguish KA from CSCC [1]. No distinctive gene expression profiles have been identified and no pathognomonic criteria to unequivocally differentiate between KA and CSCC exist [2]. Consequently, the surgical approach remains the gold standard in the management of crateriform tumors, especi-ally those arising on the face.

Background Atopic dermatitis (AD) shows differential clinical presentation in older compared with younger patients. Nevertheless, changes in the AD molecular profile with age are unknown. Objective We sought to characterize age-related changes in the AD profile. Methods We evaluated age-specific changes in lesional and nonlesional tissues and blood from patients with moderate-to-severe AD (n = 246) and age-matched control subjects (n = 71) using immunohistochemistry, quantitative real-time PCR, and Singulex in a cross-sectional study. Patients were analyzed by age group (18-40, 41-60, and ≥61 years). Results Although disease severity/SCORAD scores were similar across AD age groups (mean, approximately 60 years; P = .873), dendritic cell infiltrates (CD1b+ and FceRI+, P Conclusion The adult AD profile varies with age. Although TH1/TH17 skewing increases in both patients with AD and control subjects, patients with AD show unique decreases in TH2/TH22 polarization and normalization of epithelial abnormalities. Thus age-specific treatment approaches might be beneficial for AD.

Introduction Deficiencies in interleukin (IL)-1 receptor (IL-R) antagonist (DIRA) and IL-36R antagonist (DITRA) are rare genetic autoinflammatory diseases related to alterations in antagonists of the IL-1 pathway. IL-1 antagonists may represent therapeutic alternatives. Here, we aim to provide a scoping review of knowledge on use of IL-1-targeting drugs in DIRA and DITRA. Methods An a priori protocol was published, and the study was conducted using the methodology described in the Joanna Briggs Institute Reviewer’s Manual and the recently published PRISMA Extension for Scoping Review statement. A three-step search using MEDLINE and EMBASE databases until March 2018 with additional hand searching was performed. Data charting was performed. The search, article selection, and data extraction were carried out by two researchers independently. Results Twenty-four studies on use of anti-IL-1 drugs were included [15 studies including patients with diagnosis of DIRA (n = 19) and 9 studies including patients with diagnosis of DITRA (n = 9)]. Most studies followed a multicenter observational design. Among all patients who received treatment with anti-IL-1 drugs, nine and four mutations in IL1RN and IL36RN were found, respectively. Patients with DIRA were treated with anakinra (n = 17), canakinumab (n = 2), or rinolacept (n = 6). All patients with DITRA were treated with anakinra, and only one case was also treated with canakinumab. Time-to-response frequencies were evaluated as immediate, short, and medium–long term for DIRA (17/17, 15/17, and 9/10, respectively) and DITRA (7/9, 3/9, and 2/9, respectively). Most DITRA patients in whom anti-IL-1 treatment failed experienced good response to anti-tumor necrosis factor alpha or anti-IL-12/23 drugs. The safety profiles of treatments were similar in both diseases. Conclusions Evidence on use of anti-IL-1 drugs in DIRA and DITRA is scarce and based on observational studies. Larger studies with better methodological quality are needed to increase confidence in use of these drugs in patients with DIRA and DITRA. Electronic supplementary material The online version of this article (10.1007/s13555-018-0269-7) contains supplementary material, which is available to authorized users.

Introduction The interleukin (IL)-1 pathway has been identified as being involved in inflammatory and neoplastic skin diseases such as psoriasis, atopic dermatitis, neutrophilic dermatosis, melanoma, and squamous cell carcinoma. Drugs developed to target the IL-1 pathway are currently used to treat these pathologies, and although they are becoming more selective, they are not exempt from adverse events and high costs. Integrating the best research evidence with clinical experience and patient needs has been shown to improve care, health, and cost outcomes. This is because evidence-based guidelines rank interventions according to cost-effectiveness. However, evidence on this topic is scarce for several reasons. First, although randomized clinical trials currently provide the best evidence, they are not always available. Second, there are no secondary scientific studies that summarize the use of IL-1-targeting agents in dermatology. We therefore sought to develop an a priori protocol for broadly reviewing the available evidence on the use of IL-1-targeting drugs in the treatment of dermatological diseases. Methods We used the latest methodology to perform a scoping review as described in the Joanna Briggs Institute manual. Results/Discussion Developing and applying a methodology for evidence synthesis promotes reproducibility and increases the validity of secondary scientific investigations, making it the optimal strategy for scientifically synthesizing a broad field such as the indications for and the mechanisms of action, efficacies, safety, and costs of IL-1-targeting drugs in the treatment of dermatological diseases. Quantitative synthesis facilitates the detection of knowledge gaps and the identification of new questions that can be addressed through systematic reviews. We present an a priori protocol for exploring the available evidence on this topic.

SummaryBackground The quality of systematic reviews (SRs) and meta-analyses about psoriasis, a chronic inflammatory skin disease that severely impairs quality of life and is associated with high costs, remains unknown. Objectives To assess the methodological quality of SRs published on psoriasis. Methods After a comprehensive search in MEDLINE, EMBASE, and the Cochrane Database (PROSPERO:CDR4201604161), the quality was assessed by two raters using Assessment of Multiple Systematic Reviews (AMSTAR) tool. Article metadata and journal-related bibliometric indices were also obtained. SRs were classified as low (0-4), moderate (5-8), or high (9-11) quality. A prediction model for methodological quality was fitted using principal component and multivariate ordinal logistic regression analyses. Results We classified 220 studies as high (17.2%), moderate (55%), or low (27.7%) quality. Lower compliance rates were found for question (Q) 5 (list of studies provided, 11.3%), Q10 (publication bias assessed, 27.8%), Q4 (status of publication included, 39.5%), and Q1 (a priori design provided, 41%) AMSTAR items. Factors such as meta-analysis including (odds ratio [OR], 6.21; 95% confidence interval [CI]: 2.78-14.85), funding by academic institutions (OR, 2.89; 95% CI, 1.11-7.89), article influence score (OR, 2.13; 95% CI, 1.05-6.67), 5-year impact factor (OR, 1.34; 95% CI, 1.02-1.14), and article page count (OR, 1.08; 95% CI, 1.02-1.15) significantly predicted a higher quality; a high number of authors with a conflict of interest (OR, 0.9; 95% CI, 0.824-0.985) was significantly associated with a lower quality. Conclusions The methodological quality of SRs published about psoriasis remains suboptimal. The type of funding sources and author conflicts may compromise study quality, increasing the risk of bias. This article is protected by copyright. All rights reserved.

This research-on-research study describes effortsto develop non-Cochrane systematic reviews (SRs) by analysing demographical and time-course collaborations between international institutions using protocols registered in the International Prospective Register of Systematic Reviews (PROSPERO) or published in scientific journals. We have published an a priori protocol to develop this study. Protocols published in scientific journals were searched in MEDLINE/PubMed and Embase databases using the query terms ‘systematic review’[Title] AND ‘protocol’[Title] from February 2011 to December 2017. Protocols registered at PROSPERO during the same period were obtained by web scraping all non-Cochrane records with a Python script. After excluding protocols with less than 90% fulfilled or duplicated, they were classified as published ‘only in PROSPERO’, ‘only in journals’, or in both ‘journals and PROSPERO’. Results of data and metadata extraction using text-mining processes were curated by two reviewers. Datasets and R scripts are freely available to facilitate reproducibility. We obtained 20,814 protocols of non-Cochrane SRs. While ‘unique protocols’ by re-viewers’ institutions from 60 countries were the most frequent, to prepare ‘collaborative protocols’ a median of 6 (2-150) institutions were involved from 130 different countries. Ranked list of countries involved in overall protocol production were the UK, the U.S., Australia, Brazil, China, Canada, the Netherlands, Germany, and Italy. Most protocols were registered only in PROSPERO. However, the number of protocols published in scientific journals (924) or in both PROSPERO and journals (807) has progressively increased over the last three years. Syst Rev and BMJ Open published more than half of the total protocols. While most productive countries were involved in ‘unique’ and ‘collaborative’ protocols, less productive countries only participated in ‘collaborative’ protocols that were mainly published only in PROSPERO. Our results suggest that although most countries were involved in producing in solitary protocols of non-Cochrane SRs during the study period, it would be desirable to develop new strategies to promote international collaborations, especially with less productive countries.

Objectives The aim of this study was to describe the relationship among abstract structure, readability, and completeness, and how these features may influence social media activity and bibliometric results, considering systematic reviews (SRs) about interventions in psoriasis classified by methodological quality. Study Design and Setting Systematic literature searches about psoriasis interventions were undertaken on relevant databases. For each review, methodological quality was evaluated using the assessing the methodological quality of systematic reviews tool. Abstract extension, structure, readability, and quality and completeness of reporting were analyzed. Social media activity, which consider Twitter and Facebook mention counts, as well as Mendeley readers and Google scholar citations were obtained for each article. Analyses were conducted to describe any potential influence of abstract characteristics on review's social media diffusion. Results We classified 139 intervention SRs as displaying high/moderate/low methodological quality. We observed that abstract readability of SRs has been maintained high for last 20 years, although there are some differences based on their methodological quality. Free format abstracts were most sensitive to the increase of text readability as compared with more structured abstracts (Introduction, Methods, Results, and Discussion or eight headings), yielding opposite effects on their quality and completeness depending on the methodological quality: a worsening in low quality reviews and an improvement in those of high quality. Both readability indices and preferred reporting items of systematic reviews and meta-analyses for Abstract total scores showed an inverse relationship with social media activity and bibliometric results in high methodological quality reviews but not in those of lower quality. Conclusion Our results suggest that increasing abstract readability must be specially considered when writing free format summaries of high-quality reviews because this fact correlates with an improvement of their completeness and quality, and this may help to achieve broader social media visibility and article usage.

Background Epidemiology and the reporting characteristics of systematic reviews (SRs) and meta-analyses (MAs) are well known. However, no study has analyzed the influence of protocol features on the probability that a study’s results will be finally reported, thereby indirectly assessing the reporting bias of International Prospective Register of Systematic Reviews (PROSPERO) registration records. Objective The objective of this study is to explore which factors are associated with a higher probability that results derived from a non-Cochrane PROSPERO registration record for a systematic review will be finally reported as an original article in a scientific journal. Methods/design The PROSPERO repository will be web scraped to automatically and iteratively obtain all completed non-Cochrane registration records stored from February 2011 to December 2017. Downloaded records will be screened, and those with less than 90% fulfilled or are duplicated (i.e., those sharing titles and reviewers) will be excluded. Manual and human-supervised automatic methods will be used for data extraction, depending on the data source (fields of PROSPERO registration records, bibliometric databases, etc.). Records will be classified into published, discontinued, and abandoned review subgroups. All articles derived from published reviews will be obtained through multiple parallel searches using the full protocol “title” and/or “list reviewers” in MEDLINE/PubMed databases and Google Scholar. Reviewer, author, article, and journal metadata will be obtained using different sources. R and Python programming and analysis languages will be used to describe the datasets; perform text mining, machine learning, and deep learning analyses; and visualize the data. We will report the study according to the recommendations for meta-epidemiological studies adapted from the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement for SRs and MAs. Discussion This meta-epidemiological study will explore, for the first time, characteristics of PROSPERO records that may be associated with the publication of a completed systematic review. The evidence may help to improve review workflow performance in terms of research topic selection, decision-making regarding team selection, planning relationships with funding sources, implementing literature search strategies, and efficient data extraction and analysis. We expect to make our results, datasets, and R and Python code scripts publicly available during the third quarter of 2018.

Researchers are increasingly using on line social networks to promote their work. Some authors have suggested that measuring social media activity can predict the impact of a primary study (i.e., whether or not an article will be highly cited). However, the influence of variables such as scientific quality, research disclosures, and journal characteristics on systematic reviews and meta-analyses has not yet been assessed. The present study aims to describe the effect of complex interactions between bibliometric factors and social media activity on the impact of systematic reviews and meta-analyses about psoriasis (PROSPERO 2016: CRD42016053181). Methodological quality was assessed using the Assessing the Methodological Quality of Systematic Reviews (AMSTAR) tool. Altmetrics, which consider Twitter, Facebook, and Google+ mention counts as well as Mendeley and SCOPUS readers, and corresponding article citation counts from Google Scholar were obtained for each article. Metadata and journal-related bibliometric indices were also obtained. One-hundred and sixty-four reviews with available altmetrics information were included in the final multifactorial analysis, which showed that social media and impact factor have less effect than Mendeley and SCOPUS readers on the number of cites that appear in Google Scholar. Although a journal's impact factor predicted the number of tweets (OR, 1.202; 95% CI, 1.087-1.049), the years of publication and the number of Mendeley readers predicted the number of citations in Google Scholar (OR, 1.033; 95% CI, 1.018-1.329). Finally, methodological quality was related neither with bibliometric influence nor social media activity for systematic reviews. In conclusion, there seems to be a lack of connectivity between scientific quality, social media activity, and article usage, thus predicting scientific success based on these variables may be inappropriate in the particular case of systematic reviews.

Background Article summaries’ information and structure may influence researchers/clinicians’ decisions to conduct deeper full-text analyses. Specifically, abstracts of systematic reviews (SRs) and meta-analyses (MA) should provide structured summaries for quick assessment. This study explored a method for determining the methodological quality and bias risk of full-text reviews using abstract information alone. Methods Systematic literature searches for SRs and/or MA about psoriasis were undertaken on MEDLINE, EMBASE, and Cochrane database. For each review, quality, abstract-reporting completeness, full-text methodological quality, and bias risk were evaluated using Preferred Reporting Items for Systematic Reviews and Meta-analyses for abstracts (PRISMA-A), Assessing the Methodological Quality of Systematic Reviews (AMSTAR), and ROBIS tools, respectively. Article-, author-, and journal-derived metadata were systematically extracted from eligible studies using a piloted template, and explanatory variables concerning abstract-reporting quality were assessed using univariate and multivariate-regression models. Two classification models concerning SRs’ methodological quality and bias risk were developed based on per-item and total PRISMA-A scores and decision-tree algorithms. This work was supported, in part, by project ICI1400136 (JR). No funding was received from any pharmaceutical company. Results This study analysed 139 SRs on psoriasis interventions. On average, they featured 56.7% of PRISMA-A items. The mean total PRISMA-A score was significantly higher for high-methodological-quality SRs than for moderate- and low-methodological-quality reviews. SRs with low-bias risk showed higher total PRISMA-A values than reviews with high-bias risk. In the final model, only ’authors per review > 6’ (OR: 1.098; 95%CI: 1.012-1.194), ’academic source of funding’ (OR: 3.630; 95%CI: 1.788-7.542), and ’PRISMA-endorsed journal’ (OR: 4.370; 95%CI: 1.785-10.98) predicted PRISMA-A variability. Reviews with a total PRISMA-A score

Objectives No gold standard exists to assess methodological quality of systematic reviews (SRs). Although Assessing the Methodological Quality of Systematic Reviews (AMSTAR) is widely accepted for analyzing quality, the ROBIS instrument has recently been developed. This study aimed to compare the capacity of both instruments to capture the quality of SRs concerning psoriasis interventions. Study Design and Setting Systematic literature searches were undertaken on relevant databases. For each review, methodological quality and bias risk were evaluated using the AMSTAR and ROBIS tools. Descriptive and principal component analyses were conducted to describe similarities and discrepancies between both assessment tools. Results We classified 139 intervention SRs as displaying high/moderate/low methodological quality and as high/low risk of bias. A high risk of bias was detected for most SRs classified as displaying high or moderate methodological quality by AMSTAR. When comparing ROBIS result profiles, responses to domain 4 signaling questions showed the greatest differences between bias risk assessments, whereas domain 2 items showed the least. Conclusion When considering SRs published about psoriasis, methodological quality remains suboptimal, and the risk of bias is elevated, even for SRs exhibiting high methodological quality. Furthermore, the AMSTAR and ROBIS tools may be considered as complementary when conducting quality assessment of SRs.

Moderate-to-severe psoriasis is associated with significant comorbidity, an impaired quality of life, and increased medical costs, including those associated with treatments. Systematic reviews (SRs) and meta-analyses (MAs) of randomized clinical trials are considered two of the best approaches to the summarization of high-quality evidence. However, methodological bias can reduce the validity of conclusions from these types of studies and subsequently impair the quality of decision making. As co-authorship is among the most well-documented forms of research collaboration, the present study aimed to explore whether authors' collaboration methods might influence the methodological quality of SRs and MAs of psoriasis. Methodological quality was assessed by two raters who extracted information from full articles. After calculating total and per-item Assessment of Multiple Systematic Reviews (AMSTAR) scores, reviews were classified as low (0-4), medium (5-8), or high (9-11) quality. Article metadata and journal-related bibliometric indices were also obtained. A total of 741 authors from 520 different institutions and 32 countries published 220 reviews that were classified as high (17.2%), moderate (55%), or low (27.7%) methodological quality. The high methodological quality subnetwork was larger but had a lower connection density than the low and moderate methodological quality subnetworks; specifically, the former contained relatively fewer nodes (authors and reviews), reviews by authors, and collaborators per author. Furthermore, the high methodological quality subnetwork was highly compartmentalized, with several modules representing few poorly interconnected communities. In conclusion, structural differences in author-paper affiliation network may influence the methodological quality of SRs and MAs on psoriasis. As the author-paper affiliation network structure affects study quality in this research field, authors who maintain an appropriate balance between scientific quality and productivity are more likely to develop higher quality reviews.