Allen A. Mitchell

The Safety of Acetaminophen and Ibuprofen Among Children Younger Than Two Years Old

Background. Recently ibuprofen has been introduced as a nonprescription analgesic/antipyretic for use in children. Objective. To compare the incidence of serious adverse clinical events among children <2 years old given ibuprofen and acetaminophen to control fever. Study Design. A practitioner-based, randomized clinical trial. A total of 27u2009065 febrile children were randomized to receive acetaminophen (12 mg/kg), ibuprofen (5 mg/kg), or ibuprofen (10 mg/kg). Rates of hospitalization for acute gastrointestinal bleeding, acute renal failure, anaphylaxis, Reyes syndrome, asthma, bronchiolitis, and vomiting/gastritis were compared by randomization group. Results. The risk of hospitalization with any diagnosis in the 4 weeks after enrollment was 1.4% (95% confidence interval, 1.3%–1.6%) and did not vary by antipyretic assignment. No children were hospitalized for acute renal failure, anaphylaxis, or Reyes syndrome. Three children were hospitalized with gastrointestinal bleeding; all 3 had been assigned to treatment with ibuprofen. The risk of hospitalization with gastrointestinal bleeding among children randomized to ibuprofen was 17 per 100u2009000 (95% confidence interval, 3.5–49 per 100u2009000) but was not significantly greater than the risk among children given acetaminophen. The risk of hospitalization with asthma, bronchiolitis, or vomiting/gastritis did not differ by antipyretic assignment. Conclusions. The risk of serious adverse clinical events among children <2 years old receiving short-term treatment with either acetaminophen or ibuprofen suspension was small and did not vary by choice of medication. These data do not provide any information on the safety of these medications when used for prolonged periods or when used together, regardless of duration.

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 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.

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.

Knowledge and Practices Relating to the 2004 Acute Otitis Media Clinical Practice Guideline: A Survey of Practicing Physicians

Objective: To identify primary care physicians familiarity with the 2004 acute otitis media (AOM) clinical practice guideline and to compare their practices with its recommendations. Design: Mail survey October through December 2004 to all active physician members of the Slone Center Office-based Research Network, a national, practice-based, pediatric research network. Results: The response rate was 276 of 469 (58.8%). Overall, 90.5% had read the guideline or summaries of it. Pneumatic otoscopy was always used by 16.2%, used half the time or more by 23.1%, used less than half the time by 34.6% and never used by 26.2%. Observation is considered a reasonable option for some AOM cases by 88.0% and, over the previous 3 months, these physicians used observation a median of 10% of the time (25th and 75th percentiles, 5% and 25%, respectively). In terms of concern that the observation option may increase AOM complications, 75.6% were not at all or only slightly concerned; 24.4% were moderately or very concerned. In general, these physicians have altered their antibiotic prescribing practices for AOM towards the guidelines recommendations since its publication. However, antibiotic choices deviated most widely from the guideline in cases of AOM with severe illness, where only 17.9% follow the recommendation for high-dose amoxicillin-clavulanate, and in cases of children who fail treatment with amoxicillin-clavulanate, where only 27.7% favor the recommended intramuscular ceftriaxone. Conclusions: Most physicians in this survey are familiar with the AOM guideline, but many do not follow its diagnostic and antibiotic recommendations. Observation for selected cases is acceptable to most of these physicians and is currently used in a small proportion of cases.

When a randomised controlled trial is needed to assess drug safety : the case of paediatric ibuprofen

SummaryDrugs are frequently made available for use before risks of rare but serious reactions have been identified and quantified. While this situation may be acceptable for drugs used to treat serious conditions, greater information on safety is needed for drugs used to treat less serious conditions, and particularly those medications available without prescription. Spontaneous reports and observational studies can provide useful data in most instances, but nonrandomised studies are inadequate in the presence of confounding by indication (i.e. when patients treated with a drug differ in their underlying risk of adverse outcome from patients given alternate treatments, independent of the effect of the drug). Such is the case in the US with regard to the use of paediatric ibuprofen as an antipyretic. In this setting, a rigorous and large randomised controlled trial is needed to provide valid and statistically stable risk estimates. A trial of this kind is a feasible way to develop clinically meaningful data on safety with respect to rare but serious adverse reactions.

Xylitol Syrup for the Prevention of Acute Otitis Media

BACKGROUND: Acute otitis media (AOM) is a common childhood illness and the leading indication for antibiotic prescriptions for US children. Xylitol, a naturally occurring sugar alcohol, can reduce AOM when given 5 times per day as a gum or syrup, but a more convenient dosing regimen is needed for widespread adoption. METHODS: We designed a pragmatic practice-based randomized controlled trial to determine if viscous xylitol solution at a dose of 5 g 3 times per day could reduce the occurrence of clinically diagnosed AOM among otitis-prone children 6 months through 5 years of age. RESULTS: A total of 326 subjects were enrolled, with 160 allocated to xylitol and 166 to placebo. In the primary analysis of time to first clinically diagnosed AOM episode, the hazard ratio for xylitol versus placebo recipients was 0.88 (95% confidence interval [CI] 0.61 to 1.3). In secondary analyses, the incidence of AOM was 0.53 episodes per 90 days in the xylitol group versus 0.59 in the placebo group (difference 0.06; 95% CI –0.25 to 0.13); total antibiotic use was 6.8 days per 90 days in the xylitol group versus 6.4 in the placebo group (difference 0.4; 95% CI –1.8 to 2.7). The lack of effectiveness was not explained by nonadherence to treatment, as the hazard ratio for those taking nearly all assigned xylitol compared with those taking none was 0.93 (95% CI 0.56 to 1.57). CONCLUSIONS: Viscous xylitol solution in a dose of 5 g 3 times per day was ineffective in reducing clinically diagnosed AOM among otitis-prone children.