Variability in nitrate-reducing oral bacteria and nitric oxide metabolites in biological fluids following dietary nitrate administration: An assessment of the critical difference.

There is conflicting evidence on whether dietary nitrate supplementation can improve exercise performance. This may arise from the complex nature of nitric oxide (NO) metabolism which causes substantial inter-individual variability, within-person biological variation (CVB), and analytical imprecision (CVA) in experimental endpoints. However, no study has quantified the CVA and CVB of NO metabolites or the factors that influence their production. These data are important to calculate the critical difference (CD), defined as the smallest difference between sequential measurements required to signify a true change. The main aim of the study was to evaluate the CVB, CVA, and CD for markers of NO availability (nitrate and nitrite) in plasma and saliva before and after the ingestion of nitrate-rich beetroot juice (BR). We also assessed the CVB of nitrate-reducing bacteria from the dorsal surface of the tongue. It was hypothesised that there would be substantial CVB in markers of NO availability and the abundance of nitrate-reducing bacteria. Ten healthy male participants (age 25 ±â€¯5 years) completed three identical trials at least 6 days apart. Blood and saliva were collected before and after (2, 2.5 and 3 h) ingestion of 140 ml of BR (∼12.4 mmol nitrate) and analysed for [nitrate] and [nitrite]. The tongue was scraped and the abundance of nitrate-reducing bacterial species were analysed using 16S rRNA next generation sequencing. There was substantial CVB for baseline concentrations of plasma (nitrate 11.9%, nitrite 9.0%) and salivary (nitrate 15.3%, nitrite 32.5%) NO markers. Following BR ingestion, the CVB for nitrate (plasma 3.8%, saliva 12.0%) and salivary nitrite (24.5%) were lower than baseline, but higher for plasma nitrite (18.6%). The CD thresholds that need to be exceeded to ensure a meaningful change from baseline are 25, 19, 37, and 87% for plasma nitrate, plasma nitrite, salivary nitrate, and salivary nitrite, respectively. The CVB for selected nitrate-reducing bacteria detected were: Prevotella melaninogenica (37%), Veillonella dispar (35%), Haemophilus parainfluenzae (79%), Neisseria subflava (70%), Veillonella parvula (43%), Rothia mucilaginosa (60%), and Rothia dentocariosa (132%). There is profound CVB in the abundance of nitrate-reducing bacteria on the tongue and the concentration of NO markers in human saliva and plasma. Where these parameters are of interest following experimental intervention, the CD values presented in this study will allow researchers to interpret the meaningfulness of the magnitude of the change from baseline.

A Case-Control Study on the Impact of Ventilator-Associated Tracheobronchitis in the PICU.

OBJECTIVES: Hospital-acquired infections increase morbidity, mortality, and charges in the PICU. We implemented a quality improvement bundle directed at ventilator-associated pneumonia in our PICU in 2005. We observed an increase in ventilator-associated tracheobronchitis coincident with the near-elimination of ventilator-associated pneumonia. The impact of ventilator-associated tracheobronchitis on critically ill children has not been previously described. Accordingly, we hypothesized that ventilator-associated tracheobronchitisis associated with increased length of stay, mortality, and hospital charge. DESIGN: Retrospective case-control study. PATIENTS: Critically ill children admitted to a quaternary PICU at a free-standing academic children's hospital in the United States. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We conducted a retrospective case control study, with institutional review board approval, of 77 consecutive cases of ventilator-associated tracheobronchitis admitted to our PICU from 2004-2010. We matched each case with a control based on the following criteria (in rank order): age range (< 30 d, 30 d to 24 mo, 24 mo to 12 yr, > 12 yr), admission Pediatric Risk of Mortality III score ± 10, number of ventilator days of control group (> 75% of days until development of ventilator-associated tracheobronchitis), primary diagnosis, underlying organ system dysfunction, surgical procedure, and gender. The primary outcome measured was PICU length of stay. Secondary outcomes included ventilator days, hospital length of stay, mortality, and PICU and hospital charges. Data was analyzed using chi square analysis and p less than 0.05 was considered significant. We successfully matched 45 of 77 ventilator-associated tracheobronchitis patients with controls. There were no significant differences in age, gender, diagnosis, or Pediatric Risk of Mortality III score between groups. Ventilator-associated tracheobronchitis patients had a longer PICU length of stay (median, 21.5 d, interquartile range, 24 d) compared to controls (median, 18 d; interquartile range, 17 d), although not statistically significant (p = 0.13). Ventilator days were also longer in the ventilator-associated tracheobronchitis patients (median, 17 d; IQR, 22 d) versus control (median, 10.5 d; interquartile range, 13 d) (p = 0.01). There was no significant difference in total hospital length of stay (54 d vs 36 d; p = 0.69). PICU mortality was higher in the ventilator-associated tracheobronchitis group (15% vs 5%; p = 0.14), although not statistically significant. There was an increase in both median PICU charges ($197,393 vs $172,344; p < 0.05) and hospital charges ($421,576 vs $350,649; p < 0.05) for ventilator-associated tracheobronchitis patients compared with controls. CONCLUSIONS: Ventilator-associated tracheobronchitis is a clinically significant hospital-acquired infection in the PICU and is associated with longer duration of mechanical ventilation and healthcare costs, possibly through causing a longer PICU length of stay. Quality improvement efforts should be directed at reducing the incidence of ventilator-associated tracheobronchitis in the PICU.

Prevalence of reactive attachment disorder in a deprived population.

BACKGROUND: Reactive attachment disorder (RAD) is associated with early childhood maltreatment and has unknown population prevalence beyond infancy. AIMS: To estimate RAD prevalence in a deprived population of children. METHOD: All 1646 children aged 6-8 years old in a deprived sector of an urban UK centre were screened for RAD symptoms. Parents of high and low scorers were interviewed using semi-structured interviews probing for psychopathology and individuals likely to have RAD were offered face-to-face assessment. RESULTS: Questionnaire data were available from 92.8% of teachers and 65.8% of parents. Assessments were conducted with 50% of those invited and missing data were imputed--based on the baseline data--for the rest. We calculated that there would be 23 children with definite RAD diagnoses, suggesting that the prevalence of RAD in this population was 1.40% (95% CI 0.94-2.10). CONCLUSIONS: In this deprived general population, RAD was not rare.

Reducing catheter-associated bloodstream infections in the pediatric intensive care unit: Business case for quality improvement.

OBJECTIVE: To determine whether catheter-associated bloodstream infections were associated with increased lengths of stay in pediatric intensive care units and hospitals and increased healthcare costs in critically ill children. Previous studies have shown that hospital-acquired bloodstream infections are associated with longer stays in pediatric intensive care units, increased hospital costs, and increased hospital mortality. Catheter-associated bloodstream infections comprise the vast majority of hospital-acquired bloodstream infections. DESIGN: Retrospective, case-matched, cohort study and financial analysis. SETTING: University-affiliated children's medical center. PATIENTS: Twenty-two critically ill children with catheter-associated bloodstream infections and their matched controls. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We compared the length of stay, mortality, and hospital costs in critically ill children with catheter-associated bloodstream infections and matched controls. The presence of catheter-associated bloodstream infections extended the entire hospital length of stay by 9 days (6.5 days while in the pediatric intensive care unit) and increased hospital costs by $33,039, primarily driven by the increase in length of stay days. Quality improvement efforts directed at reducing the prevalence of catheter-associated bloodstream infections during the period of study decreased total hospital days by 354, reduced total hospital costs by $1,298,271, and reduced total costs to payers by $1,415,676. CONCLUSION: The potential cost savings from reducing or eliminating catheter-associated bloodstream infections in the pediatric intensive care unit are significant. Elimination of catheter-associated bloodstream infections will directly reduce hospital costs, improve asset utilization, and most importantly, improve clinical care.