Our data suggest that interactions between RSV and nasopharyngeal microbiota might modulate the host immune response, potentially affecting clinical disease severity.
for the Febrile Infant Working Group of the Pediatric Emergency Care Applied Research Network (PECARN) IMPORTANCE In young febrile infants, serious bacterial infections (SBIs), including urinary tract infections, bacteremia, and meningitis, may lead to dangerous complications. However, lumbar punctures and hospitalizations involve risks and costs. Clinical prediction rules using biomarkers beyond the white blood cell count (WBC) may accurately identify febrile infants at low risk for SBIs.OBJECTIVE To derive and validate a prediction rule to identify febrile infants 60 days and younger at low risk for SBIs. DESIGN, SETTING, AND PARTICIPANTS Prospective, observational study between March 2011 and May 2013 at 26 emergency departments. Convenience sample of previously healthy febrile infants 60 days and younger who were evaluated for SBIs. Data were analyzed between April 2014 and April 2018.EXPOSURES Clinical and laboratory data (blood and urine) including patient demographics, fever height and duration, clinical appearance, WBC, absolute neutrophil count (ANC), serum procalcitonin, and urinalysis. We derived and validated a prediction rule based on these variables using binary recursive partitioning analysis. MAIN OUTCOMES AND MEASURESSerious bacterial infection, defined as urinary tract infection, bacteremia, or bacterial meningitis. RESULTSWe derived the prediction rule on a random sample of 908 infants and validated it on 913 infants (mean age was 36 days, 765 were girls [42%], 781 were white and non-Hispanic [43%], 366 were black [20%], and 535 were Hispanic [29%]). Serious bacterial infections were present in 170 of 1821 infants (9.3%), including 26 (1.4%) with bacteremia, 151 (8.3%) with urinary tract infections, and 10 (0.5%) with bacterial meningitis; 16 (0.9%) had concurrent SBIs. The prediction rule identified infants at low risk of SBI using a negative urinalysis result, an ANC of 4090/μL or less (to convert to ×10 9 per liter, multiply by 0.001), and serum procalcitonin of 1.71 ng/mL or less. In the validation cohort, the rule sensitivity was 97.7% (95% CI, 91.3-99.6), specificity was 60.0% (95% CI, 56.6-63.3), negative predictive value was 99.6% (95% CI, 98.4-99.9), and negative likelihood ratio was 0.04 (95% CI, 0.01-0.15). One infant with bacteremia and 2 infants with urinary tract infections were misclassified. No patients with bacterial meningitis were missed by the rule. The rule performance was nearly identical when the outcome was restricted to bacteremia and/or bacterial meningitis, missing the same infant with bacteremia. CONCLUSIONS AND RELEVANCEWe derived and validated an accurate prediction rule to identify febrile infants 60 days and younger at low risk for SBIs using the urinalysis, ANC, and procalcitonin levels. Once further validated on an independent cohort, clinical application of the rule has the potential to decrease unnecessary lumbar punctures, antibiotic administration, and hospitalizations.
Objective Suicide is the third leading cause of death among adolescents. Many suicidal youths treated in Emergency Departments (EDs) do not receive follow-up treatment, as advocated by our National Strategy for Suicide Prevention. We compared two strategies for improving rates of follow-up treatment. Methods Randomized controlled trial in which suicidal youths at two EDs (N=181; aged 10–18) were individually randomized between April 2003 and August 2005 to one of two conditions: an enhanced mental health intervention involving a family-based cognitive-behavior therapy session in the ED designed to increase motivation for follow-up treatment and safety, supplemented by care linkage telephone contacts after discharge; or Usual ED-Care enhanced by provider education. Assessments were conducted at baseline and at about 2-months after ED/hospital discharge. The primary outcome measure was rates of outpatient mental health treatment after discharge. Results Intervention patients were significantly more likely to attend outpatient treatment, as compared to usual ED-Care patients (92% vs 76%, p=.004). The intervention group also had a significantly higher rate of psychotherapy (76% vs 49%; p=.001); combined psychotherapy and medication (58% vs 37%; p=.003); and significantly more psychotherapy visits (mean 5.3 vs 3.1; p=.003). Neither the ED intervention nor community outpatient treatment (in exploratory analyses) was significantly associated with improved clinical/functioning outcomes. Conclusions Results support efficacy of the enhanced ED intervention for improving linkage to outpatient mental health treatment, but underscore the need for improved community outpatient treatment to prevent suicide/suicide attempts and poor clinical/functioning outcomes in the high-risk youths treated in EDs for suicidality.
The development of medical countermeasures against the hematopoietic sub-syndrome of the acute radiation syndrome requires well characterized and validated animal models. The model must define the radiation dose- and time-dependent relationships for mortality and major signs of morbidity to include other organ damage that may contribute to the morbidity and mortality. Herein, we define these parameters for the nonhuman primate exposed to total-body radiation and administered medical management. A blinded, randomized study (n=48 rhesus macaques) determined the lethal dose response relationship using bilateral, 6 MV linear accelerator photon radiation to doses in the range of 7.20 to 8.90Gy at 0.80Gy minute−1. Following irradiation animals were monitored for complete blood counts, body weight, temperature, diarrhea, and hydration status for 60 days. Animals were administered medical management consisting of intravenous fluids, prophylactic antibiotics, blood transfusions, anti-diarrheals, analgesics and nutrition. The primary endpoint was survival at 60 days post irradiation; secondary endpoints included hematopoietic-related parameters, number of transfusions, incidence of documented infection, febrile neutropenia, severity of diarrhea, mean survival time of decedents and tissue histology. The study defined an LD30/60 of 7.06Gy, LD50/60 of 7.52Gy, and an LD70/60 of 7.99Gy with a relatively steep slope of 1.13 probits per linear dose. This study establishes a rhesus macaque model of the hematopoietic acute radiation syndrome and shows the marked effect of medical management on increased survival and overall mean survival time for decedents. Furthermore, following a nuclear terrorist event, medical management may be the only treatment administered at its optimal schedule.
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