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Objectives/Hypothesis To examine the incidence and survival of patients with sinonasal squamous cell carcinoma (SNSCC) between the years of 1973 and 2009 using the Surveillance, Epidemiology, and End Result (SEER) database. Study Design Retrospective cohort study using a national database. Methods The SEER registry was utilized to calculate incidence and survival trends for patients with SNSCC between 1973 and 2009. Patient data were then analyzed according to age, sex, and race. Results A total of 4,994 cases of SNSCC were identified, composed of 64.44% males and 35.56% females. Incidence trend analysis revealed a significant decrease in yearly rates from 1973 to 2009 for the overall population, females, whites, blacks, and “others” (P .05) were found when comparing survival between the last three decades. Differences in long-term survival were noted between whites, blacks, and “others,” with whites displaying the highest 20-year survival. Males and females were found to have similar long-term survival curves, with 20-year survival of 30.68% and 26.35%, respectively. Conclusions The overall incidence of SNSCC is declining. However, survival has not significantly improved in the last 3 decades. Race seems to influence the overall survival of this tumor. Future studies need to be conducted to investigate these dynamic trends related to SNSCC. Level of Evidence 2b. Laryngoscope, 124:76–83, 2014

Introduction While neonates account for a significant proportion of health care expenditures related to inpatient care for congenital heart disease, key drivers of resource utilization among this population are poorly defined. Methods Data from 2005 through 2011 were extracted from the Pediatric Health Information System for patients assigned a discharge All Patient Refined Diagnosis Related Group of 630 (neonates with birthweight >2499 g undergoing a major cardiovascular procedure). Mortality risk adjustment for patients undergoing operative interventions was performed with the Risk Adjusment in Congenital Heart Surgery (RACHS-1) score. Results A total of 13 156 cases were included in the analysis. Despite only a 3% increase in case mix index and no significant change in operative acuity over the study period (RACHS classifications of 3 or greater 67% in 2005 vs. 66% in 2011, P = .64), there were inflation-adjusted increases in both total estimated cost per case of (50% to $151 760 in 2011, P < .001), and mean charge per case (33% to $433 875 in 2011, P < .001). Pharmacy charges increased by 16% (P < .001), with agents including chlorothiazide and albumin accounting for the highest patient charges over the study period. Imaging charges increased by 42% (P < .001), with an average of 5.7 echocardiograms and $6517 in associated charges per case by 2011. While the proportion of patients receiving nitric oxide remained consistent, mean duration of administration increased by 25% to 6.6 days by 2011, accounting for average charges of $52 141 per patient exposed. Conclusions Among neonates with serious congenital heart disease, increases in both institutional costs and charges to the patient are associated with relatively consistent utilization practices in recent years. Multiinstitutional collaboration may prove useful in aligning evidence-based reductions in practice variation with limitations in resource utilization without compromising the quality of care.

There is a well-documented association of matrix metalloproteinase-9 (MMP-9) and receptor Notch-1 overexpression in colon cancer. We recently showed that MMP-9 is also upregulated in colitis, where it modulates tissue damage and goblet cell differentiation via proteolytic cleavage of Notch-1. In this study, we investigated whether MMP-9 is critical for colitis-associated colon cancer (CAC). Mice that are wild type (WT) or MMP-9 nullizygous (MMP-9−/−) were used for in vivo studies and the human enterocyte cell line Caco2-BBE was used for in vitro studies. CAC was induced in mice using an established carcinogenesis protocol that involves exposure to azoxymethane followed by treatment with dextran sodium sulfate. MMP-9−/− mice exhibited increased susceptibility to CAC relative to WT mice. Elevations in tumor multiplicity, size, and mortality were associated with increased proliferation and decreased apoptosis. Tumors formed in MMP-9−/− mice exhibited expression of p21WAF1/Cip1 and increased expression of β-catenin relative to WT mice. In vitro studies of MMP-9 overexpression showed increased Notch-1 activation with a reciprocal decrease in β-catenin. Notch and β-catenin/Wnt signaling have crucial roles in determining differentiation and carcinogenesis in gut epithelia. Despite being a mediator of proinflammatory responses in colitis, MMP-9 plays a protective role and acts as a tumor suppressor in CAC by modulating Notch-1 activation, thereby resulting in activation of p21WAF1/Cip1 and suppression of β-catenin. Cancer Res; 70(2); 792–801

A well accepted human factors concept is that poorly designed work systems can produce workload levels that pose a threat to safety and performance. The purpose of this study was to assess a systems model of workload and safety developed for nursing/healthcare. Using survey data from six nursing units in two pediatric hospitals, the study measured the relationship between self-reported workload at the unit, job, and task levels on the one hand and job dissatisfaction, burnout, and medication error likelihood on the other. Multiple linear and logistic regression revealed that staffing adequacy and medication administration workload strongly predicted the above patient and employee safety outcomes. Design priorities and strategies for future research are discussed, including the need for multiple-level approaches.

Background & Aims: There is mounting evidence that matrix metalloproteinases are the predominant proteinases expressed in the gut mucosa during active inflammatory bowel disease. We investigated the role of metalloproteinase 9 (MMP-9), a secreted gelatinase that is consistently up-regulated in both animal models and human inflammatory bowel disease and is associated with disease severity, in the pathogenesis of colitis by using mice containing a targeted deletion of the MMP-9 gene. Methods: Dextran sodium sulfate–induced colitis and Salmonella typhimurium–induced enterocolitis were used as animal models to study colitis. Results: MMP-9 activity and protein expression were absent from normal colonic mucosa but were up-regulated during experimental colitis. MMP-9−/− mice exposed to dextran sodium sulfate or salmonella had a significantly reduced extent and severity of colitis. Immunohistochemical studies showed that MMP-9 was localized to epithelial cells and granulocytes during active colitis. The immune response to systemic administration of Salmonella typhimurium was not affected in MMP-9−/− mice. Neutrophil transmigration studies and bone marrow chimeras showed that neutrophil MMP-9 is neither required for its migration nor sufficient to induce tissue damage during colitis and that epithelial MMP-9 is important for tissue damage. MMP-9 inhibited cell attachment and wound healing in the model intestinal epithelial cell line, Caco2-BBE. Conclusions: Taken together, our data suggest that MMP-9 expressed by epithelial cells may play an important role in the development of colitis by modulating cell–matrix interaction and wound healing. Thus, strategies to inhibit MMP-9 may be of potential therapeutic benefit.

The purpose of this work was to study the demographics and survival of patients diagnosed with sinonasal adenocarcinoma (SNAC) within the time period of 1973 to 2009 using the Surveillance, Epidemiology, and End Result (SEER) database.A retrospective cohort study using the U.S. National Cancer Institute's SEER registry was performed to study the demographics and survival for SNAC from 1973 to 2009. Analysis was conducted based on race, gender, and stage.In total, 1270 cases of SNAC were analyzed for demographics and survival. Males accounted for 51.6% of cases, while females accounted for 48.4% of cases, amounting to a male to female ratio of 1.06:1.00. Disease specific survival at 5, 10, 15, and 20 years was 65.2%, 50.9%, 40.9%, and 36.5%, respectively. When analyzed by gender, females had higher survival than males, although this difference was not statistically significant. When analyzed by race, the category of other, which encompasses American Indian, Asian, Hispanic, and unknown or unspecified race, was shown to have the best survival, followed by whites and blacks, respectively.SNAC is a rare tumor classically associated with occupational exposure and carries a variable prognosis. This is the first dedicated large-scale, retrospective analysis of a North American SNAC population. SNAC appears to affect both males and females equally and predominantly affects whites. Patients categorized as other had significantly better survival outcomes, while gender appeared to have no significant effect on survival.

Extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma) arising from the salivary glands is rare.Five hundred seven cases were available for frequency/incidence analysis, and 712 for relative survival and regression analysis in the Surveillance Epidemiology and End Results (SEER) database.Of the total patients, 72.98% were women, 80.47% were white, and 74.75% were ≥50 years old. The parotid gland was involved in 80.87% of cases. Ann Arbor stage at diagnosis was 53.85% IE, 18.54% IIE, and 10.06% IIIE/IV. Overall, 15-year relative survival was 78.40%. Relative survival was worst among blacks and those with advanced-stage disease. No difference was noted between those treated with surgery, radiation, or both. Statistically significant poor prognosticators included black race (hazard ratio [HR], 2.3961; 95% confidence interval [CI], 1.54-3.72; p = .0001) and stage IIIE/IV (HR, 2.3677; 95%CI, 1.36-4.11; p = .0022).Early-stage salivary gland MALT lymphoma disease may be amenable to unimodality treatment. Even patients with advanced disease have relatively high survivals.

Purpose Sinonasal rhabdomyosarcoma (SNRMS) is a rare malignancy which often presents with nasal obstruction, rhinorrhea and epistaxis. It is the most common sarcoma in children. In this study, we analyze the incidence and long-term survival for SNRMS using a national population-based database. Methods The United States National Cancer Institute’s Surveillance, Epidemiology, and End Results (SEER) registry was utilized to calculate incidence and survival trends for SNRMS between 1973 and 2009. In addition, data were grouped by age, gender, race, and histopathological subtype. Results A total of 181 cases of SNRMS were analyzed for incidence trends, showing a 1.23:1 female to male ratio. While the overall incidence of SNRMS increased by 1.02% annually over the last 20 years, this pattern was not equal amongst gender and racial groups. The incidence in males has increased, while in females incidence has decreased. An increase in incidence was noted in white and “others,” but decreased in blacks. Using a total of 314 cases for survival analysis, we found that the rate in the white population has been consistently highest with a 5-year survival of 49.45%, 10- and 20-year survival of 48.81%. Survival rates in cases of embryonal SNRMS were also consistently higher than in cases of alveolar SNRMS. Conclusion Overall incidence of SNRMS is increasing. Histologic subtype and race are important considerations in the long-term prognosis of SNRMS. Future studies will further elucidate gender and race related trends.

Inflammatory bowel disease (IBD), which includes ulcerative colitis and Crohn's disease, is a chronic inflammatory disease associated with an increased risk for colon cancer. Matrix metalloproteinases (MMPs) are the predominant proteinases expressed in the gut mucosa during active IBD. Our laboratory has previously demonstrated that epithelial-derived MMP9 is absent in normal colonic tissue but is upregulated during IBD. In this study MMP9 transgenic mice (Tg-villin-MMP9) are generated specifically to overexpress MMP9 in intestinal epithelium to examine the role and underlying mechanism by which it modulates the pathogenesis of acute colitis. Dextran sodium sulfate (3% DSS)- and Salmonella typhimurium (S.T.)-induced colitis models were used to study gut inflammation in Tg-villin-MMP9 and wild-type littermates (WT). Colonic tissue was analyzed via Western blot, histology, myeloperoxidase (MPO) assay, and quantitative PCR. Tg-villin-MMP9 mice expressed significantly increased MMP9 mRNA and protein expression at basal level. There was a significant decrease in the goblet cells, but a significant increase in proliferation and apoptosis were observed among Tg-villin-MMP9 mice compared with WT mice. There was also a significant increase in the proinflammatory chemokine Kc among Tg-villin-MMP9 compared with WT mice. Tg-villin-MMP9 exhibited a severe inflammatory response than WT mice in both DSS- and S.T.-induced colitis models as evident by greater weight loss and higher clinical score, histological score, and MPO activity, which correlated with relative levels of Kc mRNA. MMP9 expressed by intestinal epithelial cells mediates inflammation in colitis with simultaneous increase in proinflammatory cytokine Kc.

High-sensitivity Troponin-I (hs-TnI) as a marker of myocardial injury is predictive of adverse outcomes in patients with coronary artery disease (CAD). Whether the relationship between hs-TnI and outcomes is dependent on underlying CAD severity is unknown. 2826 patients without AMI (mean age 62, 64

A closed loop control process assures that a system performs within control limits. In closed loop control, the system's output feeds back directly to change the system's inputs. We describe an approach to planning and monitoring care that uses closed loop control to assure the desired performance using examples from Vanderbilt University Medical Center's ventilator management initiative. The approach has three components: an explicit end-to-end plan; a record of what is done as it is done; and an instant display of the status of each patient against their plan. The status display provides process control by showing the clinical team where correction is needed while they have time to act prospectively. Plans, displays and performance evolve together iteratively until the desired performance is achieved.

Studies have shown that ventilator weaning protocols have resulted in a reduction in duration of mechanical ventilation, ventilator-associated pneumonia, and the rate of re-intubation when compared to weaning directed by a physician. This project continuously monitors weaning status and provides feedback on each patients status. The specific aim of this project is to improve the adherence to ventilator management and ventilator weaning protocols.

Medication errors are a major concern in the Emergency Department (ED). We examined medication prescribing errors among consecutive adult ED patients during two 10-day periods before and during one 9-day period after implementing computerized provider order entry in an adult ED. 2,073 patients had 5,950, orders. Before (after) implementation there were 3.7 (2.8) potential adverse drug events, 222.0 (21.0) medication prescribing errors, and 5.1 (0) rule violations per 100 orders.

The purpose of this study was to test the hypothesis that nurse perceptions of technology they use in practice would affect their perception that they were able to provide high quality patient care. A survey assessing the variables was administered to 337 pediatric nurses from two academic freestanding pediatric hospitals in the US. Two separate equations were constructed, one to test whether technology perceptions affected individual quality of care and the other to test whether technology perceptions affected quality of care provided by the nursing unit. Nurse confidence in their ability to use hospital technology and their beliefs that the technologies were easy to use, useful, and fit their tasks are important predictors of nurse beliefs that they are able to provide quality care to their patients.

Background & Aims: We recently demonstrated that epithelial-derived matrix metalloproteinase (MMP) 9 up-regulated during inflammatory bowel disease is a critical mediator of tissue damage during colitis. MMP-9 null mice (MMP-9−/−) develop dramatically reduced inflammatory response to luminally administered colitic agents in the face of intact systemic immune response and inflammatory cell recruitment, suggesting protected epithelial barrier in these mice. In this study, we sought to address the role and mechanism by which MMP-9 influences barrier protective function. Methods: Wild-type and MMP-9−/− mice were used for in vivo studies, and the goblet cell line HT29-cl.16E and the enterocyte cell line Caco2-BBE were used for in vitro studies. Results: Compared with wild-type mice, MMP-9−/− mice had an increased number of goblet cells and MUC-2 expression. In addition, KLF-4 and Elf-3, transcription factors involved in terminal differentiation of goblet cells were up-regulated, whereas notch intracellular domain (NICD; activated Notch-1) was down-regulated in MMP-9−/− mice. These findings suggest altered epithelial cell differentiation in MMP-9−/− mice. Temporal expression of MMP-9 inversely correlated with MUC-2 expression during maturation of goblet cells. MMP-9 over expression inhibited goblet cell differentiation in vitro. Conversely, MMP-9 gene silencing in Caco2-BBE cells resulted in a change in their phenotype toward goblet cells. Finally, MMP-9 over expression or silencing in goblet cells increased or decreased Salmonella typhimurium adherence, respectively. Conclusions: MMP-9 regulates goblet cell differentiation in colon. The effect of MMP-9 on goblet cells could contribute to alteration in mucosal defense leading to inflammation. Together, our data uncover a novel function of MMP-9 in intestinal epithelial cells.

tumor progression and the development of inflammation. Inflammation and tumor grade were evaluated histologically and colonic levels of IL-12p40 and TNFαmRNAwere measured by real-time PCR. Nuclear β-catenin levels and NF-kB phosphorylation were determined by immunohistochemistry. Results: AOM-treated (6 weekly injections) IL-10-/mice developed colitis and displayed highly penetrant tumor formation under SPF conditions, while WT mice showed no evidence of intestinal inflammation and had minimal tumor formation. AOM-treated IL10-/mice showed a dramatic increase in colon tumor multiplicity and progression compared to WT mice. Tumor multiplicity increased 20-fold while progression from low to high-grade/invasive carcinoma increased by ~70% in IL10-/compared to WT mice. These tumors showed increased nuclear β-catenin accumulation and the presence of phosphorylated RelA. B. vulgatus mono-associated IL10-/mice failed to develop significant intestinal inflammation and showed greatly reduced tumor formation. AOM-treated IL10-/; MyD88-/mice showed reduced colonic expression of TNFα and IL12p40 mRNA and were devoid of neoplastic lesions compared to AOM-treated IL10-/mice. Conclusions: Bacterial-induced intestinal inflammation correlates with the progression of colon cancer in AOM-treated IL-10-/mice. The TLR/MyD88 signaling pathway is essential for the development of CAC.