Thymidine analogs, including bromodeoxyuridine, chlorodeoxyuridine, iododeoxyuridine, and tritiated thymidine, label dividing cells by incorporating into DNA during S phase of cell division and are widely employed to identify cells transplanted into the central nervous system. However, the potential for transfer of thymidine analogs from grafted cells to dividing host cells has not been thoroughly tested. We here demonstrate that graft-derived thymidine analogs can become incorporated into host neural precursors and glia. Large numbers of labeled neurons and glia were found 3-12 weeks after transplantation of thymidine analog-labeled live stem cells, suggesting differentiation of grafted cells. Remarkably, however, similar results were obtained after transplantation of dead cells or labeled fibroblasts. Our findings reveal for the first time that thymidine analog labeling may not be a reliable means of identifying transplanted cells, particularly in highly proliferative environments such as the developing, neurogenic, or injured brain.

Objective Patient-reported outcome (PRO) measures are commonly used to capture patient experience with dysphagia and to evaluate treatment effectiveness. Inappropriate application can lead to distorted results in clinical studies. A systematic review of the literature on dysphagia-related PRO measures was performed to 1) identify all currently available measures and 2) to evaluate each for the presence of important measurement properties that would affect their applicability. Design MEDLINE via the PubMed interface, the Cumulative Index of Nursing and Allied Health Literature, and the Health and Psychosocial Instrument database were searched using relevant vocabulary terms and key terms related to PRO measures and dysphagia. Three independent investigators performed abstract and full text reviews. Each study meeting criteria was evaluated using an 18-item checklist developed a priori that assessed multiple domains: 1) conceptual model, 2) content validity, 3) reliability, 4) construct validity, 6) scoring and interpretation, and 7) burden and presentation. Results Of 4950 abstracts reviewed, a total of 34 dysphagia-related PRO measures (publication year 1987 – 2014) met criteria for extraction and analysis. Several PRO measures were of high quality (MADS for achalasia, SWAL-QOL and SSQ for oropharyngeal dysphagia, PROMIS-GI for general dysphagia, EORTC-QLQ-OG25 for esophageal cancer, ROMP-swallowing for Parkinson’s disease, DSQ-EoE for eosinophilic esophagitis, and SOAL for total laryngectomy-related dysphagia). In all, 17 met at least one criterion per domain. Thematic deficiencies in current measures were evident including: 1) direct patient involvement in content development, 2) empirically justified dimensionality, 3) demonstrable responsiveness to change, 4) plan for interpreting missing responses, and 5) literacy level assessment. Conclusion This is the first comprehensive systematic review assessing developmental properties of all available dysphagia-related PRO measures. We identified several instruments with robust measurement properties in multiple diseases including achalasia, oropharyngeal dysphagia, post-surgical dysphagia, esophageal cancer, and dysphagia related to neurological diseases. Findings herein can assist clinicians and researchers in making more informed decisions in selecting the most fundamentally sound PRO measure for a given clinical, research, or quality initiative.

Objectives Patient-reported outcome (PRO) measures are often used to diagnose LPR and monitor treatment outcomes in clinical and research settings. The present systematic review was designed to identify currently available LPR-related PRO measures and to evaluate each measure’s instrument development, validation, and applicability. Data Sources MEDLINE via PubMed interface, Cumulative Index of Nursing and Allied Health Literature, and Health and Psychosocial Instrument databases were searched using relevant vocabulary and key terms related to PRO measures and LPR. Review Methods Three investigators independently performed abstract review, full-text review, and applied a previously developed checklist to critically assess measurement properties of each study meeting inclusion criteria. Results Of 4,947 studies reviewed, seven LPR-related PRO measures (publication year 1991 – 2010) met criteria for extraction and analysis. Two focused on globus and throat symptoms. Remaining measures were designed to assess LPR symptoms and monitor treatment outcomes in patients. None met all checklist criteria. Only 2/7 used patient input to devise item content and 2/7 assessed responsiveness to change. Thematic deficiencies in current LPR-related measures are inadequately demonstrated: content validity, construct validity, plan for interpretation, and literacy level assessment. Conclusion Laryngopharyngeal reflux is often diagnosed based on symptoms. Currently available LPR-related PRO measures used to symptomatically identify suspected LPR patients have disparate developmental rigor and important methodological deficiencies. Care should be exercised to understand the measurement characteristics and contextual relevance before applying these PRO measures for clinical, research, or quality initiatives.

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SummaryBackground: Symptom association probability (SAP) is thought to distinguish reflux

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In this review, we will evaluate currently available diagnostic tests and therapeutic options for patients with laryngeal signs and symptoms of reflux and briefly discuss the development and emergence of new treatments. Numerous studies have investigated the role of proton pump inhibitor therapy in this patient population, but have led to disparate and often inconsistent results. Expert commentary: While a subgroup of patients with LPR appears to respond to PPI therapy, many patients show no symptomatic improvement, particularly with respect to extraesophageal symptoms. As such, there is a vital need to explore alternative treatment options, including anti-reflux surgery, lifestyle changes, and other classes of medications to better address LPR.