Blood Eosinophil Counts and Their Variability and Risk of Exacerbations in COPD: A Population-Based Study

BackgroundThere is controversy regarding the role of blood eosinophil levels as a biomarker of exacerbation risk in chronic obstructive pulmonary disease (COPD). Our aim was to quantify blood eosinophil levels and determine the risk of exacerbations associated with these levels and their variability.MethodsObservational, retrospective, population-based study with longitudinal follow-up in patients with COPD identified in a primary care electronic medical record database in Catalonia, Spain, covering 80% of the general population. Patients were classified into 4 groups using the following cut-offs: (a) <150 cells/μl; (b) ≥150 and <300 cells/μl; (c) ≥300 and <500 cells/μl; (d) ≥500 cells/μl.ResultsA total of 57,209 patients were identified with a mean age of 70.2 years, a mean FEV1(% predicted) of 64.1% and 51.6% had at least one exacerbation the previous year. The number of exacerbations in the previous year was higher in patients with the lowest and the highest eosinophil levels compared with the intermediate groups. During follow-up the number of exacerbations was slightly higher in the group with the lowest blood eosinophil levels and in those with higher variability in eosinophil counts, but ROC curves did not identify a reliable threshold of blood eosinophilia to discriminate an increased risk of exacerbations.ConclusionsOur results do not support the use of blood eosinophil count as a reliable biomarker of the risk of exacerbation in COPD in a predominantly non-exacerbating population. Of note was that the small group of patients with the highest variability in blood eosinophils more frequently presented exacerbations.     

TFF3 Expression as Stratification Marker in Borderline Epithelial Tumors of the Ovary

Borderline tumors (BOT) of the ovary account for 10% to 20% of ovarian neoplasms. Like ovarian cancer, BOT encompass several different histological subtypes (serous, mucinous, endometrioid, clear cell, transitional cell and mixed) with serous (SBOT) and mucinous (MBOT) the most common. Current hypotheses suggest low-grade serous carcinoma may develop in a stepwise fashion from SBOT whereas the majority of high grade serous carcinomas develop rapidly presumably from inclusion cysts or ovarian surface epithelium. The pathogenesis of mucinous ovarian tumors is still puzzling. Molecular markers could help to better define relationships between such entities. Trefoil factor-3 (TFF3) is an estrogen-regulated gene associated with prognosis in different types of cancer. It has also been included in a recent marker panel predicting subtypes of ovarian carcinoma. We analyzed the expression of TFF3 by immunohistochemistry in a cohort of 137 BOT and its association with histopathological features. Overall expression rate of TFF3 was 21.9%. None of the BOT with serous and endometrioid histology displayed strong TFF3 expression. On the other hand, TFF3 was highly expressed in 61.4% of MBOT cases and 33.3% of BOT with mixed histology (P < 0.001) suggesting a potential function of the protein in that subtypes. Associations of TFF3 expression with FIGO stage and micropapillary pattern were significant in the overall cohort but confounded by their correlation with histological subtypes. The highly specific expression of TFF3 in MBOT may help to further clarify potential relationships of tumors with mucinous histology and warrants further studies.     

Variables impacting on patients' perceptions of discharge from short-stay hospitalisation or same-day surgery

The paper presents components of a study (n = 929) that was designed to examine, at one specific point in time, the hospital experience of the patient and the patient's corresponding recovery at home. Variables that captured the hospitalization and recovery experience relate to the degree of patient involvement in decisions about their treatment and discharge plans. Levels of health and recovery-related information reported by patients and their level of confidence in ability to resume regular activities once home were also measured. In general, individuals reported what many would consider having received less than optimal levels of information about their illness and recovery at home. Many patients also reported that they neither participated, nor were consulted on their needs or perceptions during their hospitalization. Expectations were that problems that patients might experience once home would have their origins in problems from within the community. However, the community resources were found to be less implicated and hospital resources more so. This suggests the importance of examining institutional issues even when one is focusing on the delivery of community services.     

Genetic effect estimates in case-control studies when a continuous variable is omitted from the model

Large-scale genome-wide analyses scans on massive numbers of various cases and controls are archived in the genetic databases that are publically available, for example, the Database of Genotypes and Phenotypes ( https://www.ncbi.nlm.nih.gov/gap/ ). These databases offer unprecscendented opportunity to study the genetic effects. Yet, the set of nongenetic variables in these databases is often brief. From the statistical literature, we know that omitting a continuous variable from a logistic regression model can result in biased estimates of odds ratios (OR), even when the omitted and the included variables are independent. We are interested in assessing what information is needed to recover the bias in the OR estimate of genotype due to omitting a continuous variable in settings when the actual values of the omitted variable are not available. We derive two estimating procedures that can recover the degree of bias based on a conditional density of the omitted variable given the disease status and the genotype or the known distribution of the omitted variable and frequency of the disease in the population. Importantly, our derivations show that omitting a continuous variable can result in either under- or over-estimation of the genetic effects. We performed extensive simulation studies to examine bias, variability, false-positive rate, and power in the model that omits a continuous variable. We show the application to two genome-wide studies of Alzheimer's disease.     

Linkage analyses of rheumatoid arthritis and related quantitative phenotypes: the GAW15 experience

The group that formed on the theme of linkage analyses of rheumatoid arthritis RA and related phenotypes (Group 10) in the Genetic Analysis Workshop 15 comprised 18 sets of investigators. Two data sets were available: one was a real set provided by the North American Rheumatoid Arthritis Consortium and collaborators in Canada, France (European Consortium Of Rheumatoid Arthritis Families) and the UK; the other was a simulated data set modelled after the real data set. Whereas a majority of the investigators analyzed the RA affection status as a binary phenotype, a few contributions considered data on correlated quantitative traits such as anti-cyclic citrullinated peptide and rheumatoid factor-immunoglobulin M. The different investigators applied a wide spectrum of linkage methods. As expected, most methods could identify the human leukocyfeantigen region on chromosome 6 as a major genetic factor for RA. In addition, some novel chromosomal regions provided significant evidence of linkage in multiple contributions in the group. In this report, we discuss the different strategies explored by the different investigators with the common goal of improving the power to detect linkage.     

Negative Affect Mediates the Relationship Between Interpersonal Problems and Binge‐Eating Disorder Symptoms and Psychopathology in a Clinical Sample: A Test of the Interpersonal Model

This study evaluated the validity of the interpersonal model of binge‐eating disorder (BED) psychopathology in a clinical sample of women with BED. Data from a cross‐sectional sample of 255 women with BED were examined for the direct effects of interpersonal problems on BED symptoms and psychopathology, and indirect effects mediated by negative affect. Structural equation modelling analyses demonstrated that higher levels of interpersonal problems were associated with greater negative affect, and greater negative affect was associated with higher frequency of BED symptoms and psychopathology. There was a significant indirect effect of interpersonal problems on BED symptoms and psychopathology mediated through negative affect. Interpersonal problems may lead to greater BED symptoms and psychopathology, and this relationship may be partially explained by elevated negative affect. The results of the study are the first to provide support for the interpersonal model of BED symptoms and psychopathology in a clinical sample of women. Copyright © 2015 John Wiley & Sons, Ltd and Eating Disorders Association.