Citations

OBJECTIVE: Despite the magnitude of the problem of catheter-associated bloodstream infections (CA-BSIs) in children, relatively little research has been performed to identify effective strategies to reduce these complications. In this study, we aimed to develop and evaluate effective catheter-care practices to reduce pediatric CA-BSIs. STUDY DESIGN AND METHODS: Our study was a multi-institutional, interrupted time-series design with historical control data and was conducted in 29 PICUs across the United States. Two central venous catheter–care practice bundles comprised our intervention: the insertion bundle of pediatric-tailored care elements derived from adult efforts and the maintenance bundle derived from the Centers for Disease Control and Prevention recommendations and expert pediatric clinician consensus. The bundles were deployed with quality-improvement teaching and methods to support their adoption by teams at the participating PICUs. The main outcome measures were the rate of CA-BSIs from January 2004 to September 2007 and compliance with each element of the insertion and maintenance bundles from October 2006 to September 2007. RESULTS: Average CA-BSI rates were reduced by 43% across 29 PICUs (5.4 vs 3.1 CA-BSIs per 1000 central-line-days; P < .0001). By September 2007, insertion-bundle compliance was 84% and maintenance-bundle compliance was 82%. Hierarchical regression modeling showed that the only significant predictor of an observed decrease in infection rates was the collective use of the insertion and maintenance bundles, as demonstrated by the relative rate (RR) and confidence intervals (CIs) (RR: 0.57 [95% CI: 0.45–0.74]; P < .0001). We used comparable modeling to assess the relative importance of the insertion versus maintenance bundles; the results showed that the only significant predictor of an infection-rate decrease was maintenance-bundle compliance (RR: 0.41 [95% CI: 0.20–0.85]; P = .017). CONCLUSIONS: In contrast with adult ICU care, maximizing insertion-bundle compliance alone cannot help PICUs to eliminate CA-BSIs. The main drivers for additional reductions in pediatric CA-BSI rates are issues that surround daily maintenance care for central lines, as defined in our maintenance bundle. Additional research is needed to define the optimal maintenance bundle that will facilitate elimination of CA-BSIs for children.

The anaphase-promoting complex/cyclosome (APC/C) E3 ubiquitin ligase functions with the E2 ubiquitin–conjugating enzyme UbcH10 in the orderly progression through mitosis by marking key mitotic regulators for destruction by the 26-S proteasome. UbcH10 is overexpressed in many human cancer types and is associated with tumor progression. However, whether UbcH10 overexpression causes tumor formation is unknown. To address this central question and to define the molecular and cellular consequences of UbcH10 overexpression, we generated a series of transgenic mice in which UbcH10 was overexpressed in graded fashion. In this study, we show that UbcH10 overexpression leads to precocious degradation of cyclin B by the APC/C, supernumerary centrioles, lagging chromosomes, and aneuploidy. Importantly, we find that UbcH10 transgenic mice are prone to carcinogen-induced lung tumors and a broad spectrum of spontaneous tumors. Our results identify UbcH10 as a prominent protooncogene that causes whole chromosome instability and tumor formation over a wide gradient of overexpression levels.

Background— Whether locomotor muscle afferent neural activity contributes to exercise hyperpnea and symptoms of dyspnea in heart failure (HF) is controversial. We examined the influence of metaboreceptor stimulation on ventilation with and without maintaining end-exercise end-tidal CO 2 levels. Methods and Results— Eleven patients with HF aged 51±5 years (ejection fraction, 32±3%; New York Heart Association class, 1.6±0.2) and 11 age- and gender-matched healthy control participants aged 43±3 years were studied. Participants underwent 3 steady-state cycling sessions at 60% of peak oxygen consumption for 4 minutes. The first exercise session was a baseline control trial. Bilateral thigh tourniquets were inflated to suprasystolic pressure at end exercise for 2 minutes during 2 of the trials (regional circulatory occlusion) with the addition of inspired CO 2 to maintain end-exercise partial pressure of end-tidal CO 2 during 1 trial (regional circulatory occlusion+CO 2 ). Minute ventilation was measured continuously throughout each trial. At 2 minutes postexercise during the baseline control trial in patients with HF, minute ventilation was 54% of end exercise, whereas the control group averaged 41% ( P =0.11). During regional circulatory occlusion in patients with HF, minute ventilation was 60% of end exercise; however, the control group averaged 35% ( P <0.001). During regional circulatory occlusion+CO 2 , the minute ventilation of patients with HF averaged 67% of end exercise, whereas the control group averaged 44% ( P <0.001). Conclusion— These data suggest that increased afferent neural activity from the large locomotor muscles associated with metabolites generated during exercise contribute to the augmented ventilatory response to exercise in patients with HF.

Abstract Background: Metabolic syndrome (MS)-related comorbidities in obesity, such as hypertension, dyslipidemia, and glucose intolerance, are increasingly recognized in children, predisposing them to early cardiovascular disease. Objective: The objective of the study was to investigate whether markers of inflammation and prothrombosis are abnormal in obese children without established MS comorbidities across puberty, as compared with lean, age-matched controls. Subjects and Methods: Obese children (body mass index &gt;95%) with normal fasting glucose, blood pressure, cholesterol and triglycerides were recruited; lean controls (body mass index 10–75%) had no first-degree relatives with MS. High-sensitivity C-reactive protein (hsCRP), IL-6, plasminogen activator inhibitor 1, and fibrinogen concentrations were measured. Body composition was assessed by waist circumference and dual-energy x-ray absorptiometry. Results: Of 623 children screened, 203 enrolled (106 males, 97 females), aged 7–18 yr, 115 obese, 88 lean (balanced for age and gender), 99 prepubertal, and 104 pubertal. Many screen failures were due to silent comorbidities. Obese subjects with insulin resistance but without MS comorbidities had about 10 times higher hsCRP concentrations than controls and higher fibrinogen, IL-6, and plasminogen activator inhibitor-1 (P &lt; 0.01 all). Differences were significant, even in the prepubertal cohort. hsCRP and fibrinogen correlated with waist circumference (r = 0.73 and 0.40, respectively) and percent fat mass (r = 0.76 and 0.47) (P &lt; 0.0001). Conclusion: Childhood obesity per se is associated with a proinflammatory and prothrombotic state before other comorbidities of the MS are present and even before the onset of puberty. Whether biomarkers like hsCRP and fibrinogen are useful in assessing cardiovascular risk and whether these abnormalities are reversible with earlier therapeutic interventions in very young obese children requires further study.

Avian influenza H5N1 viruses that have spread to a number of countries in Asia, the Middle East, and Africa have the potential to cause a pandemic. The most effective public health intervention strategy is to combine preventive vaccination with nonpharmaceutical intervention strategies and enhanced surveillance activities. H5N1 vaccines are poorly immunogenic even at high doses; an adjuvant is needed for enhancement of immunogenicity and for dose-sparing. Lack of effective, yet safe, adjuvants is the limiting factor for candidate vaccines that utilize egg-dependent or egg-independent manufacturing technologies. Hence, developing novel adjuvants is crucial for pandemic influenza vaccine development. Although the use of antiviral drugs is also an important public health countermeasure for preventing and treating influenza, the emergence of drug-resistant strains of avian H5N1 viruses underscores the need to develop not only new drugs but other novel preventive and therapeutic strategies such as vaccines.