Novel probe-based confocal laser endomicroscopy criteria and interobserver agreement for the detection of dysplasia in Barrett's esophagus.

OBJECTIVES: Probe-based confocal laser endomicroscopy (pCLE) is an imaging technique that allows real-time in vivo histological assessment of Barrett's esophagus (BE). The objectives of this study were to create and test novel pCLE criteria for dysplastic BE (phase I), and to evaluate accuracy, interobserver variability, and learning curve in dysplasia prediction (phase II) using these criteria. METHODS: In phase I, using 50 pCLE videos, a pCLE expert and gastrointestinal pathologist formulated new BE criteria by consensus. These criteria were tested and refined in an independent set of 30 pCLE videos. In phase II, a formal training session for all assessors (three each experts/trainees) was conducted. Finally, using 75 testing videos, each video was interpreted as dysplasia (high-grade dysplasia (HGD)/cancer) vs. no dysplasia and the assessors' confidence in interpretation was noted. Interobserver agreement and accuracy (95% confidence interval (CI)) were determined for BE histology prediction. RESULTS: Of multiple pCLE criteria tested (phase I), only those with ≥70% sensitivity or specificity were included in the final set: epithelial surface: saw-toothed; cells: enlarged; cells: pleomorphic; glands: not equidistant; glands: unequal in size and shape; goblet cells: not easily identified. Overall accuracy in diagnosing dysplasia was 81.5% (95% CI: 77.5-81), with no difference between experts vs. non-experts. Accuracy of prediction was significantly higher when endoscopists were "confident" about their diagnosis (98% (95-99) vs. 62% (54-70), P<0.001). Accuracy of dysplasia prediction for the first 30 videos was not different from the last 45 (93 vs. 81%, P=0.51). Overall agreement of the criteria was substantial, κ=0.61 (0.53-0.69), with no difference between experts and non-experts. CONCLUSIONS: We demonstrate the development and validation of new pCLE criteria for the prediction of HGD/cancer in BE patients. Using these criteria, this study demonstrated that overall accuracy in predicting dysplasia was high with substantial interobserver agreement. After a structured teaching session, accuracy and agreement between experienced and non-experienced observers was not different, suggesting a short learning curve.

Indicators of mania in depressed outpatients: a retrospective analysis of data from the Kansas 1500 study.

OBJECTIVE: Previous prospective studies have shown that unipolar depressed patients often switch to a manic episode. Some of these studies have reported that the conversion to bipolar disorder is predicted by an early onset of depression, a positive family history for mania, and psychotic symptoms. The present study examines the strength of the relationship between these 3 indicators, both alone and in combination, and the presence of mania in a large retrospective analysis. METHOD: 1458 consecutive admissions to a large, Midwestern university outpatient clinic between 1981 and 1986 were interviewed, and 1002 patients met DSM-III inclusive criteria for major depressive disorder. Of these, information about age at onset of depression, family history of mania, and psychotic symptoms was available on 744 outpatients. Two structured interviews were used to assess the 3 indicators. RESULTS: In this large depressed outpatient sample, the incidence of lifetime mania was 27%. Each of the 3 indicators was significantly associated with the report of mania (p < .0001 for all 3 indicators). The rates of mania increased as the number of indicators increased. Psychotic symptoms were the strongest indicator, followed by a family history of mania and an early age at onset of depression. CONCLUSION: Depressed patients with 1 or more of these 3 indicators should be monitored for the presence of bipolar disorder. Patients with 2 or more of these indicators are especially at risk to develop mania.

Enhanced cue-elicited brain activation in African American compared with Caucasian smokers: an fMRI study.

Current evidence indicates that, although African Americans (AA) are more likely to attempt to quit smoking than Caucasians (CC) in any given year, success rates are lower for AA. However, factors contributing to these differences are not well known. In order to explore potential factors, this study assessed differences in attention to smoking cues between ethnic groups. Participants underwent morning functional magnetic resonance imaging scanning while viewing images of AA models and CC models who were either smoking (smoking cues) or engaging in everyday activities (neutral cues), interspersed with a fixation baseline period. The study was conducted at the Hoglund Brain Imaging Center of the University of Kansas Medical Center in Kansas City, KS. We studied 17 smokers (eight AA, nine CC) after 12-hour abstinence and 17 non-smokers (eight AA, nine CC) matched by age, gender, years of education, and handedness. The AA and CC smoking groups were also matched for number of cigarettes smoked per day. All results are P < 0.01, corrected for whole brain. There was a strong ethnicity by condition interaction among smokers in several a priori regions of interest. AA smokers showed a greater increase in response to smoking (versus neutral cues) than CC smokers in the medial prefrontal cortex, right lateral orbitofrontal cortex, and bilateral ventrolateral prefrontal cortex. In smoking versus baseline contrasts, additional areas of greater activation were found in AA, including the right amygdala and left caudate nucleus. No significant differences in cue-elicited brain activation were found between AA and CC non-smokers. These preliminary findings demonstrate variation in brain activation in response to smoking cues between AA and CC smokers in structures known to be associated with nicotine addiction. Differences in neural response may reflect fundamental differences in attention to smoking cues, which may in turn contribute to differences in effectiveness of nicotine dependence treatments among ethnic populations.

Human odor detectability: new methodology used to determine threshold and variation.

Current ambiguity concerning the related issues of optimal means for measurement of odor sensitivity and the functional properties of the olfactory system hinders progress in basic and applied research on the human sense of smell. To address these needs, we selected n-amyl acetate (nAA) as a test odorant and developed a methodology in which participants (Ps) receive multiple presentations each session of several concentrations. Yes-no responses as to whether odor was detected are analyzed using binomial statistics, with the probability that a given proportion of yes responses (or greater) would occur by chance alone being treated as the inverse of detectability. Over the course of multiple sessions, this information is also used to maximize the collection of data in the peri-threshold region. Surprisingly, data collected over as many as 14 sessions were fit well by a single logistic regression model relating probability and concentration. Threshold concentrations, defined as those corresponding to a probability of 0.05, varied from 7.11 to 167.53 p.p.b. (v/v) for 11 Ps. Our approach and findings, if shown to be representative of other combinations of Ps and odorants, could accelerate the pace of research in human olfaction by providing a comprehensive operational definition of the limit of the olfactory system to detect odorant molecules.