Meredith Ray

The National Veteran Sleep Disorder Study: descriptive epidemiology and secular trends, 2000-2010

STUDY OBJECTIVES A large proportion of individuals affected by sleep disorders are untreated and susceptible to accidents, injuries, long-term sequelae (e.g., risk of cardiovascular disease, cancer, psychiatric disorders), and increased mortality risk. Few studies have examined the scope and magnitude of sleep disorder diagnoses in the United States (US) or factors influencing them. Veterans are particularly vulnerable to factors that elicit or exacerbate sleep disorders. METHODS This serial cross-sectional study characterized secular trends in diagnosed sleep disorders among veterans seeking care in US Veterans Health Administration facilities over an eleven-year span (FY2000-2010, n = 9,786,778). Electronic medical records from the national Veterans Administration Informatics and Computing Infrastructure database were accessed. Cases were defined using diagnostic codes specified by the American Academy of Sleep Medicine. Age-adjusted annual prevalence was summarized by sex, race, combat exposure, body mass index, and comorbid diagnoses (cardiovascular disease, cancer, mental disorders). RESULTS Sleep apnea (47%) and insomnia (26%) were the most common diagnoses among patients with any sleep disorder. There was a six-fold relative increase in total sleep disorder prevalence over the study period. Posttraumatic stress disorder, which tripled over the same time period, was associated with the highest prevalence of sleep disorders (16%) among the comorbid conditions evaluated. CONCLUSIONS The results indicate a growing need for integration of sleep disorder management with patient care and health care planning among US veterans. COMMENTARY A commentary on this article appears in this issue on page 1331.

Comparison of different cell type correction methods for genome-scale epigenetics studies

AbstractBackgroundWhole blood is frequently utilized in genome-wide association studies of DNA methylation patterns in relation to environmental exposures or clinical outcomes. These associations can be confounded by cellular heterogeneity. Algorithms have been developed to measure or adjust for this heterogeneity, and some have been compared in the literature. However, with new methods available, it is unknown whether the findings will be consistent, if not which method(s) perform better.ResultsMethods: We compared eight cell-type correction methods including the method in the minfi R package, the method by Houseman et al., the Removing unwanted variation (RUV) approach, the methods in FaST-LMM-EWASher, ReFACTor, RefFreeEWAS, and RefFreeCellMix R programs, along with one approach utilizing surrogate variables (SVAs). We first evaluated the association of DNA methylation at each CpG across the whole genome with prenatal arsenic exposure levels and with cancer status, adjusted for estimated cell-type information obtained from different methods. We then compared CpGs showing statistical significance from different approaches. For the methods implemented in minfi and proposed by Houseman et al., we utilized homogeneous data with composition of some blood cells available and compared them with the estimated cell compositions. Finally, for methods not explicitly estimating cell compositions, we evaluated their performance using simulated DNA methylation data with a set of latent variables representing “cell types”. Results: Results from the SVA-based method overall showed the highest agreement with all other methods except for FaST-LMM-EWASher. Using homogeneous data, minfi provided better estimations on cell types compared to the originally proposed method by Houseman et al. Further simulation studies on methods free of reference data revealed that SVA provided good sensitivities and specificities, RefFreeCellMix in general produced high sensitivities but specificities tended to be low when confounding is present, and FaST-LMM-EWASher gave the lowest sensitivity but highest specificity.ConclusionsResults from real data and simulations indicated that SVA is recommended when the focus is on the identification of informative CpGs. When appropriate reference data are available, the method implemented in the minfi package is recommended. However, if no such reference data are available or if the focus is not on estimating cell proportions, the SVA method is suggested.

Association of Pathologic Nodal Staging Quality With Survival Among Patients With Non-Small Cell Lung Cancer After Resection With Curative Intent.

Importance Pathologic nodal stage is the most significant prognostic factor in resectable non–small cell lung cancer (NSCLC). The International Association for the Study of Lung Cancer NSCLC staging project revealed intercontinental differences in N category–stratified survival. These differences may indicate differences not only in cancer biology but also in the thoroughness of the nodal examination. Objective To determine whether survival was affected by sequentially more stringent definitions of pN staging quality in a cohort of patients with NSCLC after resection with curative intent. Design This observational study used the Mid-South Quality of Surgical Resection cohort, a population-based database of lung cancer resections with curative intent. A total of 2047 consecutive patients who underwent surgical resection at 11 hospitals with at least 5 annual lung cancer resections in 4 contiguous US Dartmouth hospital referral regions in northern Mississippi, eastern Arkansas, and western Tennessee (>90% of the eligible population) were included. Resections were performed from January 1, 2009, through January 25, 2016. Survival was evaluated with the Kaplan-Meier method and Cox proportional hazards models. Exposures Eight sequentially more stringent pN staging quality strata included the following: all patients (group 1); those with complete resections only (group 2); those with examination of at least 1 mediastinal lymph node (group 3); those with examination of at least 10 lymph nodes (group 4); those with examination of at least 3 hilar or intrapulmonary and at least 3 mediastinal lymph nodes (group 5); those with examination of at least 10 lymph nodes, including at least 1 mediastinal lymph node (group 6); those with examination of at least 1 hilar or intrapulmonary and at least 3 mediastinal nodal stations (group 7); and those with examination of at least 1 hilar or intrapulmonary lymph node, at least 10 total lymph nodes, and at least 3 mediastinal nodal stations (group 8). Main Outcomes and Measures N category–stratified overall survival. Results Of the total 2047 patients (1046 men [51.1%] and 1001 women [48.9%]; mean [SD] age, 67.0 [9.6] years) included in the analysis, the eligible analysis population ranged from 541 to 2047, depending on stringency. Sequential improvement in the N category–stratified 5-year survival of pN0 and pN1 tumors was found from the least stringent group (0.63 [95% CI, 0.59-0.66] for pN0 vs 0.46 [95% CI, 0.38-0.54] for pN1) to the most stringent group (0.71 [95% CI, 0.60-0.79] for pN0 vs 0.60 [95% CI, 0.43-0.73] for pN1). The pN1 cohorts with 3 or more mediastinal nodal stations examined had the most striking survival improvements. More stringently defined mediastinal nodal examination was associated with better separation in survival curves between patients with pN1 and pN2 tumors. Conclusions and Relevance The prognostic value of pN stratification depends on the thoroughness of examination. Differences in thoroughness of nodal staging may explain a large proportion of intercontinental survival differences. More thorough nodal examination practice must be disseminated to improve the prognostic value of the TNM staging system. Future updates of the TNM staging system should incorporate more quality restraints.

An Efficient Approach to Screening Epigenome-Wide Data

Screening cytosine-phosphate-guanine dinucleotide (CpG) DNA methylation sites in association with some covariate(s) is desired due to high dimensionality. We incorporate surrogate variable analyses (SVAs) into (ordinary or robust) linear regressions and utilize training and testing samples for nested validation to screen CpG sites. SVA is to account for variations in the methylation not explained by the specified covariate(s) and adjust for confounding effects. To make it easier to users, this screening method is built into a user-friendly R package, ttScreening, with efficient algorithms implemented. Various simulations were implemented to examine the robustness and sensitivity of the method compared to the classical approaches controlling for multiple testing: the false discovery rates-based (FDR-based) and the Bonferroni-based methods. The proposed approach in general performs better and has the potential to control both types I and II errors. We applied ttScreening to 383,998 CpG sites in association with maternal smoking, one of the leading factors for cancer risk.

The burden of angioedema on United States emergency departments: 2006–2010

Angioedema (AE) is a condition that may prompt a visit to an emergency department (ED), and can quickly progress to airway obstruction. To optimize treatment of AE, it is necessary to understand epidemiology and practice patterns. This study measured the magnitude of AE ED visits and characterized demographics, management, frequency of airway interventions, and mortality.

Primary Palate Trauma in Patients Presenting to US Emergency Departments, 2006-2010

Importance The sequelae of palate trauma vary from minimal discomfort to major neurovascular injury. Infrequency of palate trauma and clinician unfamiliarity with the disease process may lead to variation in evaluation, treatment, and disposition in the emergency department (ED). Objectives To measure the incidence of primary palate trauma visits to US emergency departments with analysis of demographics, disposition, and repair and to determine frequency and factors associated with head and neck imaging. Design, Setting, and Participants A retrospective analysis using the Healthcare Cost and Utilization Project Nationwide Emergency Department Sample was performed of 22 094 patients presenting to US emergency departments from 2006 to 2010 with a primary diagnosis of palate trauma. Data analysis was conducted from March 29, 2016, to November 18, 2017. Main Outcomes and Measures National estimates of palate trauma were calculated from weights available within the database. Palate repair was identified by International Classification of Diseases, Ninth Revision, Clinical Modification procedure codes. Imaging was calculated from reliable Current Procedural Terminology coding facilities identified using a previously published method. Logistic models were calculated to identify clinical associations for admission, imaging, and palate repair. Results A total of 22 094 patients (13 967 male and 8121 female patients, 6 missing data on sex; median age, 2.8 years [interquartile range, 1.1-6.1 years]) with primary palate trauma presented to US emergency departments during the study period. Total hospital visits decreased from 4715 (1.58 per 100 000 people) to 3915 (1.26 per 100 000 people) during the 5-year study period. A total of 19 819 patients (89.7%) had routine discharge from the hospital, while palate repair (965 [4.4%]) and mortality (34 [0.2%]) were rare. Complicated palate trauma (odds ratio [OR], 5.32; 95% CI, 3.10-9.15), male sex (OR, 1.57; 95% CI, 1.11-2.21), codiagnosis status (OR, 2.75; 95% CI, 1.84-4.12), and residence in the Northeast vs South (OR, 2.73; 95% CI, 1.11-6.71) increased the likelihood of admission, which was infrequent (1027 patients [4.6%]). After restriction to reliable Current Procedural Terminology coding facilities, head and neck imaging occurred in 823 of 6897 patients (11.9%). Factors associated with head and neck imaging included living in a medium vs large metropolitan area (OR 1.62; 95% CI, 1.04-2.55), while living in the Midwest vs South region (OR, 0.43; 95% CI, 0.25-0.74) had a negative association with imaging. Conclusions and Relevance Although it is often suggested in the otolaryngology literature to perform imaging, primary palate trauma usually results in a routine discharge home without imaging or repair. Imaging frequency should be noted since palate trauma could have life-threatening neurovascular sequelae, which presents an opportunity to define and promote optimal management for potential neurologic sequelae in the patients who were not imaged.

PS01.39: Reach and Adoption of a Surgical Intervention to Improve Pathologic Nodal Staging Across Healthcare Systems within the US Mid-South: Topic: Surgery

infiltrative mass in the mediastinum measuring 11.5 11.5 cm with diffuse uptake, and active lesions in the lung, liver, and bone. The patient was started on treatment for TC comprising temozolomide + capecitabine, octreotide long-acting repeatable, and denosumab. Everolimus will be considered upon disease progression. Conclusion: The indolent disease behavior throughout the course of several treatments for high-grade lung NET without an impressive response led to a suspicion, then confirmed diagnosis, of a low-grade TC in this patient. While lung NET differentiation can be challenging, early suspicion in patients who neither respond nor progress on a platinum + etoposide-based doublet therapy can avoid unnecessary toxicity and the associated poor quality of life.

Identifying Activation Centers with Spatial Cox Point Processes Using fMRI Data

We developed a Bayesian clustering method to identify significant regions of brain activation. Coordinate-based meta data originating from functional magnetic resonance imaging (fMRI) were of primary interest. Individual fMRI has the ability to measure the intensity of blood flow and oxygen to a location within the brain that was activated by a given thought or emotion. The proposed method performed clustering on two levels, latent foci center and study activation center, with a spatial Cox point process utilizing the Dirichlet process to describe the distribution of foci. Intensity was modeled as a function of distance between the focus and the center of the cluster of foci using a Gaussian kernel. Simulation studies were conducted to evaluate the sensitivity and robustness of the method with respect to cluster identification and underlying data distributions. We applied the method to a meta data set to identify emotion foci centers.