Louis Vernacchio

Reduction of Respiratory Syncytial Virus (RSV) in Tracheal Aspirates in Intubated Infants by Use of Humanized Monoclonal Antibody to RSV F Protein

Thirty-five children <2 years of age mechanically ventilated for respiratory syncytial virus (RSV) infection were randomized to receive an intravenous infusion of 15 mg/kg MEDI-493 or placebo. RSV concentration was measured in tracheal secretions by plaque assay before and at 24-h intervals after treatment. The reduction in tracheal RSV concentration from day 0 to day 1 (-1.7+/-0.28 vs. -0. 6+/-0.21 log10 pfu/mL; P=.004) and from day 0 to day 2 (-2.5+/-0.26 vs. -1.0+/-0.41 log10 pfu/mL; P=.012) was significantly greater in the MEDI-493 group than in the placebo group. RSV concentration in nasal aspirates did not differ significantly between the groups. No significant differences were observed in the tracheal aspirate white blood cell count, or myeloperoxidase or eosinophilic cationic protein concentration, or in measures of disease severity between the groups. Thus, treatment with 15 mg/kg MEDI-493 intravenously was well-tolerated and significantly reduced RSV concentration in tracheal aspirates of children with respiratory failure due to RSV.

Diarrhea in American infants and young children in the community setting: incidence, clinical presentation and microbiology.

Objective: The characteristics and microbiology of the full spectrum of pediatric diarrhea occurring in the U.S. community setting are not well-understood. Methods: Six-month prospective cohort study of 604 healthy 6- to 36-month-old children recruited by the Slone Center Office-based Research Network. Results: The incidence of parent-defined diarrhea was 2.2 episodes per person-year. The median duration of diarrhea was 2 days with a median of 6 stools per episode. Outpatient visits and hospitalization were prompted by 9.7 and 0.3% of episodes, respectively. The most common microorganisms identified in healthy baseline stools were atypical enteropathogenic Escherichia coli (12.2%), enteroaggregative Escherichia coli (3.7%), Clostridium difficile (3.5%) and Clostridium perfringens (2.9%), and each of these was no more common in diarrhea stools. In contrast, all of the viruses analyzed were more prevalent in diarrhea specimens than in baseline specimens: enteric adenovirus (5.7% diarrhea versus 1.4% baseline), rotavirus (5.2% versus 1.4%), astrovirus (3.5% versus 1.4%), Sapporo-like virus (3.0% versus 0.8%) and norovirus (1.9% versus 0.8%). A likely pathogen was detected in 20.6% of diarrhea specimens. Vomiting and ≥16 stools in an episode were predictive of isolating a pathogen from the stool, each with a relative risk of ∼2. Conclusions: Healthy young children in this study experienced more than 2 cases of diarrhea per person-year, but most were brief and do not require medical attention. Although most diarrhea-associated pathogens were viruses, no likely pathogen was found in almost 80% of cases; possible etiologies for these cases include currently unknown gastrointestinal infections, nongastrointestinal illnesses and dietary/environmental factors.

Management of acute otitis media after publication of the 2004 AAP and AAFP clinical practice guideline.

OBJECTIVES: Observation without initial antibiotic therapy was accepted as an option for acute otitis media (AOM) management in the 2004 American Academy of Pediatrics and American Academy of Family Physicians clinical practice guideline. The guideline also recommended amoxicillin as the first-line treatment for most children, and analgesic treatment to reduce pain if it was present. Our objective was to compare the management of AOM after publication of the 2004 guideline. PATIENTS AND METHODS: We analyzed the National Ambulatory Medical Care Survey, 2002–2006 (N = 1114), which occurred in US physicians offices. The patients were children aged 6 months to 12 years who were diagnosed with AOM. The time comparisons were the 30-month periods before and after the guideline. The main outcome was the encounter rate at which no antibiotic-prescribing was reported. Secondary outcomes were the identification of factors associated with encounters at which no antibiotic-prescribing was reported and antibiotic- and analgesic-prescribing rates. RESULTS: The rate of AOM encounters at which no antibiotic-prescribing was reported did not change after guideline publication (11%–16%; P = .103). Independent predictors of an encounter at which no antibiotic-prescribing was reported were the absence of ear pain, absence of reported fever, and receipt of an analgesic prescription. After guideline publication, the rate of amoxicillin-prescribing increased (40%–49%; P = .039), the rate of amoxicillin/clavulanate-prescribing decreased (23%–16%; P = .043), the rate of cefdinir-prescribing increased (7%–14%; P = .004), and the rate of analgesic-prescribing increased (14%–24%; P = .038). CONCLUSIONS: Although management of AOM without antibiotics has not increased after the publication of the 2004 American Academy of Pediatrics and American Academy of Family Physicians clinical practice guideline, children who did not receive antibiotics were more likely to have mild infections. In accordance with the guideline, the prescribing of amoxicillin and analgesics has increased. Contrary to the guideline, the prescribing of amoxicillin/clavulanate has decreased, whereas the prescribing of cefdinir has increased.

Combined schedule of 7-valent pneumococcal conjugate vaccine followed by 23-valent pneumococcal vaccine in children and young adults with sickle cell disease☆☆☆★★★

We compared the immunogenicity of 7-valent pneumococcal-conjugate vaccine plus 23-valent pneumococcal vaccine to immunization with 23-valent vaccine only in individuals > or = 2 years of age with sickle cell disease. IgG pneumococcal antibody concentrations were higher in the combined schedule group with no increase in side effects observed after immunization with 23-valent vaccine.

Medication use among children <12 years of age in the United States: results from the Slone Survey.

OBJECTIVES: Using data from the Slone Survey, we sought to define the prevalence of over-the-counter and prescription medication use among US children <12 years of age and to determine the prevalence and patterns of use of the most commonly used medications. METHODS: The Slone Survey was a random-digit-dial telephone survey of medication use in the previous 7 days for a representative sample of the US population. Between February 1998 and April 2007, we enrolled 2857 children 0 to 11 years of age from the 48 contiguous US states. RESULTS: The survey response rate was 61%. Overall, 56% of children had used ≥1 medication product in the 7 days preceding the interview, with 15%, 7.1%, 3.1%, and 1.9% taking 2, 3, 4, and ≥5 medications, respectively, during that time period. Twenty percent of children took ≥1 prescription-only medications, but <6% used ≥2 prescription-only drugs within a given week. Fewer than 0.5% of children were reported to have used any particular herbal product. The most commonly used over-the-counter medication products were acetaminophen alone, multivitamins, and ibuprofen alone. The most commonly used prescription-only medications across all age groups were amoxicillin, albuterol, and multivitamins with fluoride. The most commonly consumed active ingredients (excluding vitamins) were acetaminophen, iron, ibuprofen, and various cough/cold ingredients (pseudoephedrine, dextromethorphan, and various first-generation antihistamines). CONCLUSIONS: The majority of US children <12 years of age use ≥1 medication product in a given week. The preponderance of pediatric medication exposure involves over-the-counter products.

Cough and Cold Medication Use by US Children, 1999–2006: Results From the Slone Survey

OBJECTIVE. Pediatric cough and cold medications are widely marketed in the United States, but the precise patterns of use among children are not known. Such information is especially important given recent reports suggesting that these medications are responsible for previously underappreciated serious adverse events and deaths among children. We sought to describe the prevalence and patterns of pediatric use of cough and cold medications, with particular attention to use among young children. METHODS. We analyzed data on the use of cough and cold medications, defined as any oral medication that contains ≥1 antitussive, decongestant, expectorant, and/or first-generation antihistamine active ingredients, among 4267 US children who were younger than 18 years and enrolled during 1999–2006 in the Slone Survey, a national random-digit-dial telephone survey of medication use by the US population. RESULTS. In a given week, a cough and cold medication was used by 10.1% of US children. Exposure was highest to decongestants (6.3%; mostly pseudoephedrine) and first-generation antihistamines (6.3%; most common were chlorpheniramine, diphenhydramine, and brompheniramine), followed by antitussives (4.1%; mostly dextromethorphan) and expectorants (1.5%; almost exclusively guaifenesin). Multiple-ingredient products accounted for 64.2% of all cough and cold medications used. Exposure to antitussives, decongestants, and first-generation antihistamines was highest among 2- to 5-year-olds (7.0%, 9.9%, and 10.1%, respectively) followed by children who were younger than 2 years (5.9%, 9.4%, and 7.6%, respectively); expectorant use was low in all age groups. The use of cough and cold medications declined from 1999 through 2006. CONCLUSIONS. Approximately 1 in 10 US children uses a cough and cold medication in a given week. The especially high prevalence of use among children of young age is noteworthy, given concerns about potential adverse effects and the lack of data on the efficacy of cough and cold medications in this age group.

Management of acute otitis media by primary care physicians: trends since the release of the 2004 American Academy of Pediatrics/American Academy of Family Physicians clinical practice guideline.

OBJECTIVES. In 2004, the American Academy of Pediatrics and the American Academy of Family Physicians released a clinical practice guideline on the management of acute otitis media that included endorsement of an observation option for selected cases and recommendations of specific antibiotics. We sought to describe primary care physicians current management of acute otitis media to compare it with the guidelines recommendations and describe trends since 2004. DESIGN. We used a mail survey from March through June 2006 within the Slone Center Office-Based Research Network, a national practice-based pediatric research network. RESULTS. The response rate was 299 (62.7%) of 477. The observation option was considered reasonable by 83.3%, compared with 88.0% in 2004, and was used in a median of 15% of acute otitis media cases over the previous 3 months. The most common physician-identified barriers to the use of the observation option were parental reluctance (83.5%) and the cost and difficulty of follow-up of children who do not improve (30.9%). In terms of antibiotic choices for acute otitis media, agreement with the guidelines antibiotic recommendation for 4 common clinical scenarios was as follows: high-dose amoxicillin for acute otitis media with nonsevere symptoms (57.2%), high-dose amoxicillin-clavulanate for acute otitis media with severe symptoms (12.7%), high-dose amoxicillin-clavulanate for cases that failed to respond to amoxicillin (42.8%), and intramuscular ceftriaxone for cases that failed to respond to treatment with amoxicillin-clavulanate (16.7%). Each of these proportions declined from 2004. CONCLUSIONS. Most primary care physicians accept the concept of an observation option for acute otitis media but use it only occasionally. Antibiotics prescribed for acute otitis media differ markedly from the guidelines recommendations, and the difference has increased since 2004.

Effect of monophosphoryl lipid A (MPL®) on T-helper cells when administered as an adjuvant with pneumocococcal-CRM197 conjugate vaccine in healthy toddlers

As new vaccines are developed, novel adjuvants may play an important role in eliciting an effective immune response. We evaluated the safety and adjuvant properties of monophosphoryl lipid A (MPL in 129 healthy toddlers immunized with two doses of nine-valent pneumococcal-CRM(197) protein conjugate vaccine (PCV9) combined with 10, 25, or 50 micro g of MPL with or without alum (AlPO(4)). Vaccine-specific humoral and cell-mediated responses were examined following the second dose of study vaccine. All doses of MPL were well-tolerated and a dose-dependent effect of MPL on specific cellular responses was observed. The 10 micro g MPL dose significantly enhanced CRM(197)-specific T-cell proliferation (P=0.02) and interferon-gamma (INF-gamma) production (P=0.009) compared to responses of controls who received PCV9 with AlPO(4). In contrast, CRM(197)-specific T-cell proliferation and interferon-gamma production of the 50 micro g MPL/AlPO(4) group were decreased when compared to controls although these differences did not reach statistical significance. IL-5 and IL-13 responses after immunization showed a similar pattern with increased production in the 10 micro g MPL group and decreased production in the 50 micro g MPL/AlPO(4) group compared to controls. There were no differences in serum IgG antibody concentrations to the nine vaccine pneumococcal capsular polysaccharides and carrier protein between the MPL-containing and control vaccine groups. These findings demonstrate a dose-dependent effect of MPL on T-helper cell type 1 (TH-1) responses to the carrier protein and also suggest an effect on T-helper cell type 2 (TH-2) responses.

Comparison of an Opsonophagocytic Assay and IgG ELISA to Assess Responses to Pneumococcal Polysaccharide and Pneumococcal Conjugate Vaccines in Children and Young Adults with Sickle Cell Disease

Children with sickle cell disease were immunized with either 2 doses of 7-valent pneumococcal conjugate vaccine followed by 1 dose of 23-valent pneumococcal polysaccharide vaccine or a single dose of 23-valent vaccine. Functional antibodies to 7 vaccine serotypes were measured by a flow cytometric opsonophagocytic assay (OPA) and compared with IgG anticapsular polysaccharide antibody concentrations measured by ELISA. Moderate correlations were found between OPA and ELISA antibody titers for all 7 serotypes (r values, 0.41-0.70; P<.001 for all serotypes). After immunization with 23-valent vaccine, geometric mean antibody titers by OPA were significantly higher in the combined schedule group for 5 of 7 vaccine serotypes but were significantly higher for only 2 of 7 serotypes as measured by ELISA. The ability of OPA to show a greater differential response to the 2 immunization schedules used in this study suggests that it may be useful in the evaluation of immunization regimens involving pneumococcal conjugate vaccines.

Validity of Parental Reporting of Recent Episodes of Acute Otitis Media: A Slone Center Office-based Research (SCOR) Network Study

Background: The validity of parental reporting of children’s health outcomes is an important methodological issue in community-based pediatric research. We assessed the validity of parents’ reports of their children’s acute otitis media (AOM) history over the previous month in a pilot study of xylitol for AOM prevention. Methods: Parents of children participating in a study conducted in the Slone Center Office-Based Research (SCOR) Network were interviewed monthly for 3 months and asked whether their child had been diagnosed with AOM in the previous month. A blinded physician reviewed medical records. Results from parental interviews and medical records were compared by correlation analysis. Results: Medical records were obtained for 102 of 120 children (85.0%); 272 monthly interviews were completed. κ for the agreement between parental reports and medical records was 0.88 [95% confidence intervals (CI): 0.76 to 0.94]. The positive predictive value of a parental report of an AOM episode within the previous month was 85.0%, and the negative predictive value was 99.1%. Conclusions: The results of this study suggest that parental reporting of children’s recent AOM history correlates well with medical records. Parental interview is a reasonable approach to collecting data on recent AOM outcomes, particularly in large-scale community-based studies where obtaining medical records is often impractical.