Dysphagia Screening for Pneumonia Prevention in a Cancer Hospital: Results of a Quality/Safety Initiative.

OBJECTIVE: Hospital-acquired aspiration pneumonia remains a rare but potentially devastating problem. The best means by which to prevent aspiration in a cancer hospital population has not been evaluated. The aim of this study was to evaluate the impact of dysphagia screening on aspiration pneumonia rates in an acute care oncology hospital. METHODS: A prospective single-institution quality improvement dysphagia screening protocol at a comprehensive cancer center. Effect of dysphagia screening implemented in 2016 on hospital-acquired aspiration pneumonia rates coded "aspiration pneumonitis due to food/vomitus" was compared with rates from 2014 to 2015 prior to implementation. Screening compliance, screening outcomes, patient demographics, and medical data were reviewed as part of a post hoc analysis. RESULTS: Of 12,392 admissions in 2014 to 2016, 97 patients developed aspiration pneumonia during their hospitalization. No significant change in aspiration pneumonia rate was seen during the dysphagia screening year when compared to prior years (baseline, 7.36; screening year, 8.78 per 1000 discharges; P = .33). Sixty-eight of the cases (66%) were associated with emesis/gastrointestinal obstruction or perioperative aspiration and only 15 (15%) with oropharyngeal dysphagia. Multivariate analysis found that patients admitted to gastrointestinal surgery had an aspiration risk equivalent to patients admitted to head and neck, thoracic, and pulmonary services (odds ratio, 0.65; P = .2). DISCUSSION: Nursing-initiated dysphagia screening did not decrease aspiration pneumonia rates. The causes of aspiration-associated pneumonia were heterogeneous. Aspiration of intestinal contents is a more common source of hospital-acquired pneumonia than oropharyngeal dysphagia.

Validated genomic approach to study differentially expressed genes in complex tissues.

Microarray-based genomic techniques allow the simultaneous determination of relative levels of expression of a large number of genes. Studies of the transcriptome in complex neurobiological systems are uniquely demanding due to the heterogeneous nature of these cells. Most brain regions contain a large variety of cell populations that are closely intermingled. The expression of any specific gene may be restricted to a subpopulation of cells, and changes in gene expression may occur in only a small fraction of the cells expressing that transcript. Due to this dilution effect, many genes of interest are expected to have relatively low levels of expression in tissue homogenates. Furthermore, biologically significant differences in expression may result in only small fold-changes. Therefore genomic approaches using brain dissections must be optimized to identify potentially regulated transcripts and differential expression should be confirmed using quantitative assays. We evaluated the effects of increasing tissue complexity on detection of regulated transcripts in focused microarray studies using a mouse cell line, mouse hypothalamus and mouse cortex. Regulated transcripts were confirmed by quantitative real-time PCR. As tissue complexity increased, distinguishing significantly regulated genes from background variation became increasingly more difficult. However, we found that cDNA microarray studies using regional brain dissections and appropriate numbers of replicates could identify genes showing less than 2-fold regulation and that most regulated genes identified fell within this range.

Conserved helix 7 tyrosine acts as a multistate conformational switch in the 5HT2C receptor. Identification of a novel "locked-on" phenotype and double revertant mutations.

Studies in many rhodopsin-like G-protein-coupled receptors are providing a general scheme of the structural processes underlying receptor activation. Microdomains in several receptors have been identified that appear to function as activation switches. However, evidence is emerging that these receptor proteins exist in multiple conformational states. To study the molecular control of this switching process, we investigated the function of a microdomain involving the conserved helix 7 tyrosine in the serotonin 5HT2C receptor. This tyrosine of the NPXXY motif was substituted for all naturally occurring amino acids. Three distinct constitutively active receptor phenotypes were found: moderate, high, and "locked-on" constitutive activity. In contrast to the activity of the other receptor mutants, the high basal signaling of the locked-on Y7.53N mutant was neither increased by agonists nor decreased by inverse agonists. The Y7.53F mutant was uncoupled. Computational modeling based on the rhodopsin crystal structure suggested that Y7.53 interacts with the conserved aromatic ring at position 7.60 in the recently identified helix 8 domain. This provided a basis for seeking revertant mutations to correct the defective function of the Y7.53F receptor. When the Y7.53F receptor was mutated at position 7.60, the wild-type phenotype was restored. These results suggest that Y7.53 and Y7.60 contribute to a common functional microdomain connecting helices 7 and 8 that influences the switching of the 5HT2C receptor among multiple active and inactive conformations.