Citations

Objectives Socioeconomic status (SES) is a well-established risk factor for many health outcomes. Recently, we developed an SES measure based on 4 housing-related characteristics (termed HOUSES) and demonstrated its ability to assess health disparities. In this study, we aimed to evaluate whether fewer housing-related characteristics could be used to provide a similar representation of SES. Study setting and participants We performed a cross-sectional study using parents/guardians of children aged 1–17 years from 2 US Midwestern counties (n=728 in Olmsted County, Minnesota, and n=701 in Jackson County, Missouri). Primary and secondary outcome measures For each participant, housing-related characteristics used in the formulation of HOUSES (assessed housing value, square footage, number of bedrooms and number of bathrooms) were obtained from the local government assessor's offices, and additional SES measures and health outcomes with known associations to SES (obesity, low birth weight and smoking exposure) were collected from a telephone survey. Housing characteristics with the greatest contribution for predicting the health outcomes were added to formulate a modified HOUSES index. Results Among the 4 housing characteristics used in the original HOUSES, the strongest contributions for predicting health outcomes were observed from assessed housing value and square footage (combined contribution ranged between 89% and 96%). Based on this observation, these 2 were used to calculate a modified HOUSES index. Correlation between modified HOUSES and other SES measures was comparable to the original HOUSES for both locations. Consistent with the original HOUSES formula, the strongest association with modified HOUSES was observed with smoking exposure (OR=0.24 with 95% CI 0.11 to 0.49 for comparing participants in highest HOUSES vs lowest group; overall p<0.001). Conclusions The modified HOUSES requires only 2 readily available housing characteristics thereby improving the feasibility of using this index as a proxy for SES in multiple communities, especially in the US Midwestern region.

ObjectiveTo investigate clinical and pathologic aspects of IgG4‐related disease (IgG4‐RD) in non‐Asian populations.MethodsWe conducted a retrospective review of the medical records of patients with IgG4‐RD who presented to an academic medical center from January 1994 to September 2012.ResultsAmong 166 patients identified, the median age at diagnosis was 61 years (interquartile range [IQR] 49–70 years), 75% were male, and 80% were white. The median number of organs involved was 2 (IQR 2–3). When organs were grouped according to anatomic system, the hepatopancreaticobiliary system was most commonly involved (77%). The median highest serum IgG4 level during the clinical course was 215 mg/dl (IQR 122–466). Forty‐three patients (26%) had a normal serum IgG4 level. Seventy‐nine pathology specimens were available for immunostaining. The median number of IgG4+ cells was 37 (IQR 25–82) per high‐power field, with an IgG4+:IgG+ ratio of 0.50 (IQR 0.32–0.68). Among 151 patients who received medical therapy, 72 (48%) received steroid‐sparing agents because of relapse, recurrence, or corticosteroid intolerance. Of the 66 patients who were newly diagnosed, started on corticosteroid monotherapy as the initial treatment, and followed up at our institution, 30 (45%) experienced relapse or recurrence despite an initial favorable response. The number of organs involved had a significant impact on time to relapse or recurrence, with a hazard ratio of 1.48 (95% confidence interval [95% CI] 1.12–1.93) (P < 0.01) in multivariate analysis. The standardized incidence ratio of malignancy was 4.5 (95% CI 1.5–7.5).Conclusion. IgG4‐RD is a multisystem disorder that commonly affects older men and has a propensity for relapse, recurrence, and malignancy.

ObjectivesBipolar disorder (BD) is a complex disease associated with various hereditary traits, including a higher body mass index (BMI). In a prior genome‐wide association study, we found that BMI modified the association of rs12772424 – a common variant in the gene encoding transcription factor 7‐like 2 (TCF7L2) – with risk for BD. TCF7L2 is a transcription factor in the canonical Wnt pathway, involved in multiple disorders, including diabetes, cancer and psychiatric conditions. Here, using an independent sample, we evaluated 26 TCF7L2 single nucleotide polymorphisms (SNPs) to explore further the association of BD with the TCF7L2–BMI interaction.MethodsUsing a sample of 662 BD cases and 616 controls, we conducted SNP‐level and gene‐level tests to assess the evidence for an association between BD and the interaction of BMI and genetic variation in TCF7L2. We also explored the potential mechanism behind the detected associations using human brain expression quantitative trait loci (eQTL) analysis.ResultsThe analysis provided independent evidence of an rs12772424–BMI interaction (p = 0.011). Furthermore, while overall there was no evidence for SNP marginal effects on BD, the TCF7L2–BMI interaction was significant at the gene level (p = 0.042), with seven of the 26 SNPs showing SNP–BMI interaction effects with p < 0.05. The strongest evidence of interaction was observed for rs7895307 (p = 0.006). TCF7L2 expression showed a significant enrichment of association with the expression of other genes in the Wnt canonical pathway.ConclusionsThe current study provides further evidence suggesting that TCF7L2 involvement in BD risk may be regulated by BMI. Detailed, prospective assessment of BMI, comorbidity, and other possible contributing factors is necessary to explain fully the mechanisms underlying this association.

The clinical utility of microbiome biomarkers depends on the reliable and reproducible nature of comparative results. Underappreciation of the variation associated with common demographic, health, and behavioral factors may confound associations of interest and generate false positives. Here, we present the Midwestern Reference Panel (MWRP), a resource for comparative gut microbiome studies conducted in the Midwestern United States. We analyzed the relationships between demographic and health behavior-related factors and the microbiota in this cohort, and estimated their effect sizes. Most variables investigated were associated with the gut microbiota. Specifically, body mass index (BMI), race, sex, and alcohol use were significantly associated with microbial β-diversity (P < 0.05, unweighted UniFrac). BMI, race and alcohol use were also significantly associated with microbial α-diversity (P < 0.05, species richness). Tobacco use showed a trend toward association with the microbiota (P < 0.1, unweighted UniFrac). The effect sizes of the associations, as quantified by adjusted R 2 values based on unweighted UniFrac distances, were small (< 1% for all variables), indicating that these factors explain only a small percentage of overall microbiota variability. Nevertheless, the significant associations between these variables and the gut microbiota suggest that they could still be potential confounders in comparative studies and that controlling for these variables in study design, which is the main objective of the MWRP, is important for increasing reproducibility in comparative microbiome studies.

Abstract Rationale Surgical lung biopsy is often required for a confident multidisciplinary diagnosis of idiopathic pulmonary fibrosis (IPF). Alternative, less-invasive biopsy methods, such as bronchoscopic lung cryobiopsy (BLC), are highly desirable. Objectives To address the impact of BLC on diagnostic confidence in the multidisciplinary diagnosis of IPF. Methods In this cross-sectional study we selected 117 patients with fibrotic interstitial lung disease without a typical usual interstitial pneumonia pattern on high-resolution computed tomography. All cases underwent lung biopsies: 58 were BLC, and 59 were surgical lung biopsy (SLB). Two clinicians, two radiologists, and two pathologists sequentially reviewed clinical-radiologic findings and biopsy results, recording at each step in the process their diagnostic impressions and confidence levels. Measurements and Main Results We observed a major increase in diagnostic confidence after the addition of BLC, similar to SLB (from 29 to 63%, P = 0.0003 and from 30 to 65%, P = 0.0016 of high confidence IPF diagnosis, in the BLC group and SLB group, respectively). The overall interobserver agreement in IPF diagnosis was similar for both approaches (BLC overall kappa, 0.96; SLB overall kappa, 0.93). IPF was the most frequent diagnosis (50 and 39% in the BLC and SLB group, respectively; P = 0.23). After the addition of histopathologic information, 17% of cases in the BLC group and 19% of cases in the SLB group, mostly idiopathic nonspecific interstitial pneumonia and hypersensitivity pneumonitis, were reclassified as IPF. Conclusions BLC is a new biopsy method that has a meaningful impact on diagnostic confidence in the multidisciplinary diagnosis of interstitial lung disease and may prove useful in the diagnosis of IPF. This study provides a robust rationale for future studies investigating the diagnostic accuracy of BLC compared with SLB.

Background Socioeconomic status (SES) is an important predictor for outcomes of chronic diseases. However, it is often unavailable in clinical data. We sought to determine whether an individual housing-based SES index termed HOUSES can influence the likelihood of multiple chronic conditions (MCC) and hospitalisation in a community population. Methods Participants were residents of Olmsted County, Minnesota, aged >18 years, who were enrolled in Mayo Clinic Biobank on 31 December 2010, with follow-up until 31 December 2011. Primary outcome was all-cause hospitalisation over 1 calendar-year. Secondary outcome was MCC determined through a Minnesota Medical Tiering score. A logistic regression model was used to assess the association of HOUSES with the Minnesota tiering score. With adjustment for age, sex and MCC, the association of HOUSES with hospitalisation risk was tested using the Cox proportional hazards model. Results Eligible patients totalled 6402 persons (median age, 57 years; 25th–75th quartiles, 45–68 years). The lowest quartile of HOUSES was associated with a higher Minnesota tiering score after adjustment for age and sex (OR (95% CI) 2.4 (2.0 to 3.1)) when compared with the highest HOUSES quartile. Patients in the lowest HOUSES quartile had higher risk of all-cause hospitalisation (age, sex, MCC-adjusted HR (95% CI) 1.53 (1.18 to 1.98)) compared with those in the highest quartile. Conclusions Low SES, as assessed by HOUSES, was associated with increased risk of hospitalisation and greater MCC health burden. HOUSES may be a clinically useful surrogate for SES to assess risk stratification for patient care and clinical research.