Aerodigestive Approach to Pediatric Chronic Cough.

Chronic cough is defined as cough lasting more than 4 weeks in children aged 14 years or older. Normal children, without pathophysiology, can cough up to more than 30 times a day. When cough occurs pathologically, it is often more often and can be divided into specific and nonspecific cough types. Inputs from otolaryngology, pulmonary medicine, and gastroenterology, along with other specialties in an aerodigestive team setting, allow a team approach to consider a wide variety of causes of cough and coordinate diagnostic procedures with treatment.

Cost Efficacy of Rapid Whole Genome Sequencing in the Pediatric Intensive Care Unit.

The diagnostic and clinical utility of rapid whole genome sequencing (rWGS) for critically ill children in the intensive care unit (ICU) has been substantiated by multiple studies, but comprehensive cost-effectiveness evaluation of rWGS in the ICU outside of the neonatal age group is lacking. In this study, we examined cost data retrospectively for a cohort of 38 children in a regional pediatric ICU (PICU) who received rWGS. We identified seven of 17 patients who received molecular diagnoses by rWGS and had resultant changes in clinical management with sufficient clarity to permit cost and quality adjusted life years (QALY) modeling. Cost of PICU care was estimated to be reduced by $184,846 and a total of 12.1 QALYs were gained among these seven patients. The total cost of rWGS for patients and families for the entire cohort (38 probands) was $239,400. Thus, the net cost of rWGS was $54,554, representing $4,509 per QALY gained. This quantitative, retrospective examination of healthcare utilization associated with rWGS-informed medicine interventions in the PICU revealed approximately one-third of a QALY gained per patient tested at a cost per QALY that was approximately one-tenth of that typically sought for cost-effective new medical interventions. This evidence suggests that performance of rWGS as a first-tier test in selected PICU children with diseases of unknown etiology is associated with acceptable cost-per-QALY gained.

Clinical implications of pulmonary nodules detected in children.

INTRODUCTION: The management of children found to have pulmonary nodules is not well established. We determined how often diagnostic testing was pursued, the outcome of diagnostic testing, and how often pulmonary nodules were given a definitive diagnosis. METHOD: A retrospective review of patients found to have pulmonary nodules. Patients with oncologic diagnoses were excluded. Data collected included number of nodules, presence of pre-existing systemic disease, laboratory testing, presence of respiratory symptoms, repeat imaging, biopsy result, and final diagnosis. RESULTS: We identified 88 patients, of which 56 (64%) had a single nodule, 21 (24%) had a pre-existing nononcologic systemic disease, and four patients (5%) had a new systemic disease identified at the same time the nodule(s) was found. In otherwise healthy patients presenting with a solitary nodule, 94% did not have a definitive diagnosis and none went on to be diagnosed with systemic disease. Serum infectious work-up result for tuberculosis, coccidioidomycosis, histoplasmosis, or aspergillosis was not significantly different between single and multiple nodule/systemic illness groups. No previously healthy patients presenting with a solitary nodule were later diagnosed with malignancy. CONCLUSION: Diagnostic workup for a solitary pulmonary nodule was often inconclusive, especially if the patient did not have symptoms at presentation. Pulmonary nodules were not the sole presenting sign of systemic disease for any subjects. We suggest that in an otherwise healthy pediatric patient found to have an asymptomatic single pulmonary nodule, observation without laboratory work-up or repeat imaging is a reasonable option.

Metagenomic sequencing and evaluation of the host response in the pediatric aerodigestive population.

OBJECTIVES: To assess the diagnostic utility of metagenomic sequencing in pediatric aerodigestive clinic patients being evaluated for chronic aspiration. We hypothesize that using a metagenomics platform will aid in the identification of microbes not found on standard culture. STUDY DESIGN AND METHODS: Twenty-four children referred to an aerodigestive clinic were enrolled in a prospective, single-site, cross-sectional cohort study. At the time of clinical evaluation under anesthesia, two samples were obtained: an upper airway sample and a sample from bronchoalveolar lavage (BAL). Samples were sent for routine culture and analyzed using Explify® Respiratory, a CLIA Laboratory Developed Test which identifies respiratory commensals and pathogens through RNA and DNA sequencing. Since RNA was sequenced in the course of the metagenomic analysis to identify organisms (RNA viruses and bacteria), the sequencing approach also captured host derived messenger RNA during sample analysis. This incidentally obtained host transcriptomic data were analyzed to evaluate the host immune response. The results of these studies were correlated with the clinical presentation of the research subjects. RESULTS: In 10 patients, organisms primarily associated with oral flora were identified in the BAL. Standard culture was negative in three patients where clinical metagenomics led to a result with potential clinical significance. Transcriptomic data correlated with the presence or absence of dysphagia as identified on prior videofluoroscopic evaluation of swallowing. CONCLUSIONS: Clinical metagenomics allows for simultaneous analysis of the microbiota and the host immune response from BAL samples. As the technologies in this field continue to advance, such testing may improve the diagnostic evaluation of patients with suspected chronic aspiration.

HIV-1 genital shedding is suppressed in the setting of high genital antiretroviral drug concentrations throughout the menstrual cycle.

BACKGROUND: It is not known if fluctuations in genital tract antiretroviral drug concentrations correlate with genital virus shedding in human immunodeficiency virus (HIV)-infected women on antiretroviral therapy (ART). METHODS: Among 20 HIV-infected women on ART (tenofovir [TFV], emtricitabine [FTC], and ritonavir-boosted atazanavir [ATV]) with suppressed plasma virus loads, blood and cervicovaginal samples collected twice weekly for 3 weeks were tested for antiretroviral concentrations, HIV-1 RNA, and proviral DNA. RESULTS: Cervicovaginal:plasma antiretroviral concentration ratios were highest for FTC (11.9, 95% confidence interval [CI], 8.66-16.3), then TFV (3.52, 95% CI, 2.27-5.48), and ATV (2.39, 95% CI, 1.69-3.38). Within- and between-person variations in plasma and genital antiretroviral concentrations were observed. Low amounts of genital HIV-1 RNA (<50 copies/mL) were detected in 45% of women at 16% of visits. Genital HIV-1 DNA was detected in 70% of women at 35% of visits. Genital virus detection was associated with higher concentrations of mucosal leukocytes but not with genital antiretroviral concentrations, menstrual cycle phase, bacterial vaginosis, genital bleeding, or plasma virus detection. CONCLUSIONS: Standard doses of ART achieved higher genital than plasma concentrations across the menstrual cycle. Therapeutic ART suppresses genital virus shedding throughout the menstrual cycle, even in the presence of factors reported to increase virus shedding.

Prevalence and clinical outcome of hyperglycemia in the perioperative period in noncardiac surgery.

OBJECTIVE: Hospital hyperglycemia, in individuals with and without diabetes, has been identified as a marker of poor clinical outcome in cardiac surgery patients. However, the impact of perioperative hyperglycemia on clinical outcome in general and noncardiac surgery patients is not known. RESEARCH DESIGN AND METHODS: This was an observational study with the aim of determining the relationship between pre- and postsurgery blood glucose levels and hospital length of stay (LOS), complications, and mortality in 3,184 noncardiac surgery patients consecutively admitted to Emory University Hospital (Atlanta, GA) between 1 January 2007 and 30 June 2007. RESULTS: The overall 30-day mortality was 2.3%, with nonsurvivors having significantly higher blood glucose levels before and after surgery (both P < 0.01) than survivors. Perioperative hyperglycemia was associated with increased hospital and intensive care unit LOS (P < 0.001) as well as higher numbers of postoperative cases of pneumonia (P < 0.001), systemic blood infection (P < 0.001), urinary tract infection (P < 0.001), acute renal failure (P = 0.005), and acute myocardial infarction (P = 0.005). In multivariate analysis (adjusted for age, sex, race, and surgery severity), the risk of death increased in proportion to perioperative glucose levels; however, this association was significant only for patients without a history of diabetes (P = 0.008) compared with patients with known diabetes (P = 0.748). CONCLUSIONS: Perioperative hyperglycemia is associated with increased LOS, hospital complications, and mortality after noncardiac general surgery. Randomized controlled trials are needed to determine whether perioperative diabetes management improves clinical outcome in noncardiac surgery patients.

Hyperglycemia during total parenteral nutrition: an important marker of poor outcome and mortality in hospitalized patients.

OBJECTIVE: To determine the effect of total parenteral nutrition (TPN)-induced hyperglycemia on hospital outcome. RESEARCH DESIGN AND METHODS: The study determined whether blood glucose values before, within 24 h, and during days 2-10 of TPN are predictive of hospital complications and mortality. RESULTS: Subjects included a total of 276 patients receiving TPN for a mean duration of 15 +/- 24 days (+/-SD). In multiple regression models adjusted for age, sex, and diabetes status, mortality was independently predicted by pre-TPN blood glucose of 121-150 mg/dl (odds ratio [OR] 2.2, 95% CI 1.1-4.4, P = 0.030), 151-180 mg/dl (3.41, 1.3-8.7, P = 0.01), and >180 mg/dl (2.2, 0.9-5.2, P = 0.077) and by blood glucose within 24 h of >180 mg/dl (2.8, 1.2-6.8, P = 0.020). A blood glucose within 24 h of >180 mg/dl was associated with increased risk of pneumonia (OR 3.1, 95% CI 1.4-7.1) and acute renal failure (2.3, 1.1-5.0). CONCLUSIONS: Hyperglycemia is associated with increased hospital complications and mortality in patients receiving TPN.