Citations

ABSTRACTObjectives:Small bowel intraepithelial lymphocytosis (IELs) with normal villous architecture is a relatively common finding, often of uncertain significance. The aims of our study were to determine the prevalence of this finding, its clinical associations, its specificity for celiac disease (CD), and whether histologic clues exist that increase the specificity for CD in this setting, all in the pediatric population.Methods:The Mayo Clinic electronic pathology database was searched between January 1, 2000 and December 31, 2009 for patients younger than 18 years who had the terms “normal villi” and “increased intraepithelial lymphocytes” in their small bowel biopsy reports. All of the slides were reviewed to confirm the histologic findings. Demographic, serologic, pathologic, and clinical informations were obtained.Results:Among 1290 duodenal biopsies obtained from children during the years 2000 and 2009, 56 (4.3%) were noted to have “normal villous architecture with increased intraepithelial lymphocytes.” In the 54 patients not known to have CD before biopsy, 48 (89%) had serologic testing for CD. Of these 48 patients, 9 were labeled with CD, although only 5 of 9 met the definite criteria for the diagnosis, based on a combination of serologic markers, human leukocyte antigen haplotyping, and response to gluten‐free diet. No clinical features pointed to a diagnosis of CD. There was no correlation between CD and number of IELs, but patients with newly diagnosed CD were more likely to have a tip‐heavy lymphocyte distribution. Other diagnoses made during the study period and in follow‐up were inflammatory bowel disease (5), Helicobacter pylori infection (3), medication‐related injury (10), and systemic autoimmune disorders (2).Conclusions:Increased IELs with normal villous architecture in small bowel biopsies are clinically important in children, and are associated with a new definite diagnosis of CD in 9% of pediatric patients. Even at this low sensitivity, clinical work‐up for CD is mandated in all of the patients with this finding.

Abstract: To ensure that participants in randomized controlled trials are protected from harm, interim analyses and review of results by an independent data monitoring committee have become standard practice. If an analysis of accumulating data partway through a trial reveals an unanticipated degree of benefit or toxicity, or differences in outcomes between the intervention and control groups are so unimpressive that any prospect of a positive result with the planned sample size is extremely unlikely, investigators may stop the trial earlier than originally scheduled. The practice of stopping randomized controlled trials early is, however, problematic, especially if the trial is stopped for apparent benefit. Concerns in trials stopped early for apparent benefit include appropriate interpretation of results and ethical problems concerning trial participants, clinicians, and society as a whole. In this article, we review the epidemiology of trials stopped early and illustrate some of the problems and controversies associated with stopping randomized controlled trials early for apparent benefit. Finally, we offer guidance for clinicians, those running clinical trials, and authors of systematic reviews.

Adults with intellectual disabilities (ID) have low levels of physical activity and higher than average rates of related chronic health conditions. Understanding correlates of their physical activity participation may improve health promoting interventions. Forty-two adults with ID participated in a physical activity study. Physical activity knowledge and skills, awareness of recommendations and demographic characteristics were analyzed for their association with moderate-to-vigorous physical activity (MVPA) participation measured by accelerometers. Five variables were significantly correlated with MVPA. Body mass index was inversely correlated with MVPA, and gender, job location, job tasks, and place of residence were all significantly associated with MVPA. Understanding correlates of physical activity in this population will help inform disability service and health promotion professionals in future research and health intervention design.

Examining the patient's subjective experience in prospective clinical comparative effectiveness research (CER) of oncology treatments or process interventions is essential for informing decision making. Patient-reported outcome (PRO) measures are the standard tools for directly eliciting the patient experience. There are currently no widely accepted standards for developing or implementing PRO measures in CER. Recommendations for the design and implementation of PRO measures in CER were developed via a standardized process including multistakeholder interviews, a technical working group, and public comments. Key recommendations are to include assessment of patient-reported symptoms as well as health-related quality of life in all prospective clinical CER studies in adult oncology; to identify symptoms relevant to a particular study population and context based on literature review and/or qualitative and quantitative methods; to assure that PRO measures used are valid, reliable, and sensitive in a comparable population (measures particularly recommended include EORTC QLQ-C30, FACT, MDASI, PRO-CTCAE, and PROMIS); to collect PRO data electronically whenever possible; to employ methods that minimize missing patient reports and include a plan for analyzing and reporting missing PRO data; to report the proportion of responders and cumulative distribution of responses in addition to mean changes in scores; and to publish results of PRO analyses simultaneously with other clinical outcomes. Twelve core symptoms are recommended for consideration in studies in advanced or metastatic cancers. Adherence to methodologic standards for the selection, implementation, and analysis/reporting of PRO measures will lead to an understanding of the patient experience that informs better decisions by patients, providers, regulators, and payers.

The present study examines treatment length and timing of exposure from two child anxiety disorders clinics. Data regarding symptoms and treatment characteristics for 28 youth were prospectively obtained through self, parent, and therapist report at each session. Information regarding length of treatment, timing of exposure initiation, and drop-out rates were compared with those obtained through efficacy and effectiveness trials of manualized treatment for anxious youth. Findings from the authors’ clinical data revealed significantly shorter treatment duration with exposures implemented sooner than in the previous studies. Dropout rates were significantly higher than in the efficacy trial but comparable with the effectiveness trial. Outcome data from a subset of eight patients revealed large effect sizes. These findings suggest that effective treatment can be shorter and more focused on exposure than is often outlined in manuals and have important implications for outcome research and dissemination.