OBJECTIVES: To derive and internally validate a prediction model for the identification of febrile infants #60 days old at low probability of invasive bacterial infection (IBI). METHODS: We conducted a case-control study of febrile infants #60 days old who presented to the emergency departments of 11 hospitals between July 1, 2011 and June 30, 2016. Infants with IBI, defined by growth of a pathogen in blood (bacteremia) and/or cerebrospinal fluid (bacterial meningitis), were matched by hospital and date of visit to 2 control patients without IBI. Ill-appearing infants and those with complex chronic conditions were excluded. Predictors of IBI were identified with multiple logistic regression and internally validated with 10-fold cross-validation, and an IBI score was calculated. RESULTS: We included 181 infants with IBI (155 [85.6%] with bacteremia without meningitis and 26 [14.4%] with bacterial meningitis) and 362 control patients. Twenty-three infants with IBI (12.7%) and 138 control patients (38.1%) had fever by history only. Four predictors of IBI were identified (area under the curve 0.83 [95% confidence interval (CI): 0.79-0.86]) and incorporated into an IBI score: age ,21 days (1 point), highest temperature recorded in the emergency department 38.0-38.4°C (2 points) or $38.5°C (4 points), absolute neutrophil count $5185 cells per mL (2 points), and abnormal urinalysis results (3 points). The sensitivity and specificity of a score $2 were 98.8% (95% CI: 95.7%-99.9%) and 31.3% (95% CI: 26.3%-36.6%), respectively. All 26 infants with meningitis had scores $2. CONCLUSIONS: Infants #60 days old with fever by history only, a normal urinalysis result, and an absolute neutrophil count ,5185 cells per mL have a low probability of IBI. WHAT'S KNOWN ON THIS SUBJECT: Commonly used risk-stratification criteria for febrile infants were either developed .2 decades ago in studies that included relatively few infants with bacteremia and/or bacterial meningitis or include procalcitonin, which is not readily available in some hospitals. WHAT THIS STUDY ADDS: A newly derived score is highly sensitive for the identification of non-ill-appearing febrile infants #60 days old with invasive bacterial infection. Infants with fever by history only, normal urinalysis results, and an absolute neutrophil count ,5185 cells per mL had a low probability of infection.
An HSV infection was uncommon in young infants evaluated for CNS infection, particularly in the second month of life. Evidence-based approaches to the evaluation for HSV in young infants are needed.
Evidence shows that both poor physical fitness and obesity are linked to low-grade inflammation and inflammatory diseases. However, their relative roles on inflammation and underlying mechanisms remain unclear. Given the inhibitory effect of catecholamines on inflammatory cytokine production, we speculated that compromised responsiveness of immune cells’ beta adrenergic receptors (β-ARs) to agonists may be associated with constitutively elevated levels of inflammatory cytokines. We examined circulating levels of inflammatory cytokines TNF, IL-1β, IL-6 and β-AR sensitivity of, 70 overweight or obese compared to 26 normal-weight, otherwise healthy individuals in order to investigate the associations among obesity, physical fitness, and low-grade inflammation and to examine the role of β-ARs in these relationships. Cardiorespiratory fitness was determined by VO2peak (ml/kg/min) via a treadmill exercise. Beta-AR sensitivity was evaluated by measuring the degree of inhibition in lipopolysaccharides-stimulated monocytic intracellular TNF production by isoproterenol. In all participants, BMI, which was initially a predictor of IL-1β and IL-6 levels independent of demographic characteristics, no longer significantly predicted them after controlling for fitness levels. Among the overweight or obese participants, greater cardiorespiratory fitness was a strong predictor of lower levels of TNF and IL-1β after controlling for the covariates. When β-AR sensitivity was controlled for, however, fitness was no longer a significant predictor of those cytokines. Monocytic β-AR sensitivity was negatively associated with inflammatory marker levels and diminished in obese individuals; however, when fitness was controlled for, the significant weight group differences in β-AR sensitivity disappeared. Our findings indicate that better cardiorespiratory fitness protects against obesity-related low-grade inflammation and β-AR desensitization. Given the significance of β-AR function in pathogenesis of various diseases, clinical implications of its role in the fitness-inflammation association among the obese are profound.
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