Andrew J. Thomas

Bayesian Hierarchical Model for Correcting Signal Saturation in Microarrays Using Pixel Intensities

Pixel saturation occurs when the pixel intensity exceeds the scanner upper threshold of detection and the recorded pixel intensity is then truncated at the threshold. Truncation of the pixel intensity causes the estimates of gene expression (i.e., intensity) to be biased. Microarray experiments are commonly affected by saturated pixels; as a result all higher level analyses are made on these biased gene expression estimates. In this paper, we propose a method for improving the quality of the signal for cDNA microarrays by making use of several scans at varying scanner sensitivities. For each spot, pixel level intensity readings are given as input to a Bayesian hierarchical model. The model uses the pixel intensities of the spot to provide a posterior distribution of the true expression level of the corresponding genes. The parameters of the hierarchical model are estimated jointly with these expression levels, thus performing an integrated analysis of the measurement data. The method improves in all ranges the accuracy with which intensities can be estimated and extends the dynamic range of measured gene expression at the high end. The method is generic and can be applied to data from any organism and for imaging with any scanner. Results from a real data set illustrate an improved precision in the estimation of the expression of genes compared to what can be achieved by applying standard methods and using only a single scan.

Surgeon and hospital cost variability for septoplasty and inferior turbinate reduction

Septoplasty and turbinate reduction (STR) is a common procedure for which cost reduction efforts may improve value. The purpose of this study was to identify sources of variation in medical facility and surgeon costs associated with STR, and whether these costs correlated with short‐term complications.

Elective Neck Dissection for Head and Neck Cutaneous Squamous Cell Carcinoma with Skull Base Invasion.

Objectives Skull base invasion from cutaneous squamous cell carcinoma (cSCC) via perineural spread affects survival and the rate of regional metastasis. Our objective is to investigate the factors associated with elective neck dissection (END) in this population and the survival difference with END compared with observation for patients with a cN0 neck. Study Design Case series with chart review. Setting Academic. Subjects and Methods Patients were treated surgically for head and neck cSCC with skull base invasion via perineural spread with a cN0 neck from 2004 to 2014. Clinicopathologic data were collected and analyzed. Primary outcomes were disease-free survival (DFS) and overall survival (OS). Results Fifty-nine patients met inclusion criteria: 28 underwent an END and 31 underwent neck observation. Free tissue transfer reconstruction was significantly associated with END (P < .001). Patients treated with an END had significantly improved 5-year DFS (57% and 32%, P = .042) and OS (60% and 37%, P = .036) compared with those who were observed and a significantly reduced rate of regional recurrence (9% and 37%, P = .024). The rate of occult nodal metastasis identified with END was 36% and is approximately equal to the regional failure rate of the neck observation group (37%). Conclusion END was more commonly used in cases requiring free tissue transfer. The use of END for head and neck cSCCs that have invaded the skull base is not routinely performed but was found to be associated with a survival advantage and reduced regional recurrence rate.

Nasal obstruction has a limited impact on sleep quality and quality of life in patients with chronic rhinosinusitis.

Nasal obstruction is a cardinal symptom in diagnosing chronic rhinosinusitis (CRS), and decreased sleep quality (SQ) and quality of life (QOL) are commonly reported in CRS. It is, however, unclear what role nasal obstruction severity plays in this decreased SQ and QOL. Using validated instruments, we evaluated the relationship between nasal obstruction severity, SQ, and QOL.

Hospital cost of pediatric patients with complicated acute sinusitis

OBJECTIVE Review costs for pediatric patients with complicated acute sinusitis. METHODS A retrospective case series of patients in a pediatric hospital was created to determine hospital costs using a standardized activity-based accounting system for inpatient treatment between November 2010 and December 2014. Children less than 18 years of age who were admitted for complicated acute sinusitis were included in the study. Demographics, length of stay, type of complication and cost of care were determined for these patients. RESULTS The study included 64 patients with a mean age of 10 years. Orbital cellulitis (orbital/preseptal/postseptal cellulitis) accounted for 32.8% of patients, intracranial complications (epidural/subdural abscess, cavernous sinus thrombosis) for 29.7%, orbital abscesses (subperiosteal/intraorbital abscesses) for 25.0%, potts puffy tumor for 7.8%, and other (including facial abscess and dacryocystitis) for 4.7%. The average length of stay was 5.7 days. The mean cost per patient was

Lack of correlation between patient reported location and severity of facial pain and radiographic burden of disease in chronic rhinosinusitis.

20,748. Inpatient floor costs (31%) and operating room costs (18%) were the two greatest expenditures. The major drivers in variation of cost between types of complications included pediatric intensive care unit stays and pharmacy costs. CONCLUSION Although complicated acute sinusitis in the pediatric population is rare, this study demonstrates a significant financial impact on the health care system. Identifying ways to reduce unnecessary costs for these visits would improve the value of care for these patients.

Nonparaganglioma Jugular Foramen Tumors

Facial pain is a cardinal symptom of chronic rhinosinusitis (CRS) with significant impacts on patient treatment selection, quality of life, and outcomes. The association between facial pain and CRS disease severity has not been systematically evaluated with validated, facial pain–specific questionnaires. Our objective was to measure pain location, severity, and interference in patients with CRS, and correlate these to the location and severity of radiographic evidence of disease.

Prevention of sinonasal inflammation by a synthetic glycosaminoglycan.

This article discusses the epidemiology, presentation, and diagnostic work-up of nonparaganglioma jugular foramen tumors, and the management options and predicted outcomes. Paragangliomas are the most common jugular foramen tumors, but other nonparagangliomas are important to consider in a differential for jugular foramen tumors. This article specifically focuses on jugular foramen schwannomas, meningiomas, metastatic disease, and regional pathologies that may extend to the jugular foramen, such as endolymphatic sac tumors, chordomas, and chondrosarcomas. Operative approaches to these tumors are also reviewed.

Full likelihood analysis of genetic risk with variable age at onset disease - combining population-based registry data and demographic information.

Glycosaminoglycans (GAGs) are polysaccharides that are distributed on respiratory epithelial cells, endothelial cells, and submucosal glands. Uniquely positioned, certain GAGs exhibit anti‐inflammatory properties in respiratory diseases and serve important roles in repairing mucosal surfaces and modulating mucociliary clearance. We hypothesized that topical administration of a synthetic GAG (GM‐0111) would prevent sinonasal inflammation in a mouse model of rhinosinusitis (RS).

Mortality risk in patients with chronic rhinosinusitis and its association to asthma: Chronic rhinosinusitis and mortality

Background In genetic studies of rare complex diseases it is common to ascertain familial data from population based registries through all incident cases diagnosed during a pre-defined enrollment period. Such an ascertainment procedure is typically taken into account in the statistical analysis of the familial data by constructing either a retrospective or prospective likelihood expression, which conditions on the ascertainment event. Both of these approaches lead to a substantial loss of valuable data. Methodology and Findings Here we consider instead the possibilities provided by a Bayesian approach to risk analysis, which also incorporates the ascertainment procedure and reference information concerning the genetic composition of the target population to the considered statistical model. Furthermore, the proposed Bayesian hierarchical survival model does not require the considered genotype or haplotype effects be expressed as functions of corresponding allelic effects. Our modeling strategy is illustrated by a risk analysis of type 1 diabetes mellitus (T1D) in the Finnish population-based on the HLA-A, HLA-B and DRB1 human leucocyte antigen (HLA) information available for both ascertained sibships and a large number of unrelated individuals from the Finnish bone marrow donor registry. The heterozygous genotype DR3/DR4 at the DRB1 locus was associated with the lowest predictive probability of T1D free survival to the age of 15, the estimate being 0.936 (0.926; 0.945 95% credible interval) compared to the average population T1D free survival probability of 0.995. Significance The proposed statistical method can be modified to other population-based family data ascertained from a disease registry provided that the ascertainment process is well documented, and that external information concerning the sizes of birth cohorts and a suitable reference sample are available. We confirm the earlier findings from the same data concerning the HLA-DR3/4 related risks for T1D, and also provide here estimated predictive probabilities of disease free survival as a function of age.