ObjectivesThe aim of this study was to develop a critical appraisal (CA) tool that addressed study design and reporting quality as well as the risk of bias in cross-sectional studies (CSSs). In addition, the aim was to produce a help document to guide the non-expert user through the tool.DesignAn initial scoping review of the published literature and key epidemiological texts was undertaken prior to the formation of a Delphi panel to establish key components for a CA tool for CSSs. A consensus of 80% was required from the Delphi panel for any component to be included in the final tool.ResultsAn initial list of 39 components was identified through examination of existing resources. An international Delphi panel of 18 medical and veterinary experts was established. After 3 rounds of the Delphi process, the Appraisal tool for Cross-Sectional Studies (AXIS tool) was developed by consensus and consisted of 20 components. A detailed explanatory document was also developed with the tool, giving expanded explanation of each question and providing simple interpretations and examples of the epidemiological concepts being examined in each question to aid non-expert users.ConclusionsCA of the literature is a vital step in evidence synthesis and therefore evidence-based decision-making in a number of different disciplines. The AXIS tool is therefore unique and was developed in a way that it can be used across disciplines to aid the inclusion of CSSs in systematic reviews, guidelines and clinical decision-making.

Objectives To identify patient‐reported experience measures (PREMs), assess their validity and reliability, and assess any bias in the study design of PREM validity and reliability testing. Data Sources/Study Setting Articles reporting on PREM development and testing sourced from MEDLINE, CINAHL and Scopus databases up to March 13, 2018. Study Design Systematic review. Data Collection/Extraction Methods Critical appraisal of PREM study design was undertaken using the Appraisal tool for Cross‐Sectional Studies (AXIS). Critical appraisal of PREM validity and reliability was undertaken using a revised version of the COSMIN checklist. Principal Findings Eighty‐eight PREMs were identified, spanning across four main health care contexts. PREM validity and reliability was supported by appropriate study designs. Internal consistency (n = 58, 65.2 percent), structural validity (n = 49, 55.1 percent), and content validity (n = 34, 38.2 percent) were the most frequently reported validity and reliability tests. Conclusions Careful consideration should be given when selecting PREMs, particularly as seven of the 10 validity and reliability criteria were not undertaken in ≥50 percent of the PREMs. Testing PREM responsiveness should be prioritized for the application of PREMs where the end user is measuring change over time. Assessing measurement error/agreement of PREMs is important to understand the clinical relevancy of PREM scores used in a health care evaluation capacity.

Bladder cancer is approximately three times more common in men as compared to women. We and others have previously investigated the contribution of androgens and the androgen receptor (AR) to bladder cancer. JMJD2A and LSD1 are recently discovered AR coregulator proteins that mediate AR-dependent transcription via recently described histone-lysine demethylation (KDM) mechanisms. We used immunohistochemistry to examine JMJD2A, LSD1 and AR expression in 72 radical cystectomy specimens, resulting in evaluation of 129 tissue samples (59 urothelial carcinoma, 70 benign). We tested levels of these proteins for statistical association with clinicopathologic variables and patient survival. Expression of these markers was also assessed in human bladder cancer cell lines. The effects of pharmacological inhibition of LSD1 on the proliferation of these bladder cancer cells was determined. JMJD2A and AR levels were significantly lower in malignant versus benign urothelium, while increased LSD1 levels were observed in malignant urothelium relative to benign. A significant reduction in all three proteins occurred with cancer stage progression, including muscle invasion (JMJD2A/LSD1/AR), extravesical extension (JMJD2A/LSD1) and lymph node metastasis (JMJD2A/AR). Lower JMJD2A intensity correlated with additional poor prognostic features, including lymphovascular invasion, concomitant carcinoma in situ and tobacco usage, and predicted significantly worse overall survival. Pharmacological inhibition of LSD1 suppressed bladder cancer cell proliferation and androgen induced transcription. Our results support a novel role for the AR-KDM complex in bladder cancer initiation and progression, identify JMJD2A as a promising prognostic biomarker, and demonstrate targeting of the KDM activity as an effective potential approach for bladder cancer growth inhibition.