Gregory F. Hayden

A Controlled Trial of Acyclovir for Chickenpox in Normal Children

BACKGROUND Chickenpox, the primary infection caused by the varicella-zoster virus, affects more than 3 million children a year in the United States. Although usually self-limited, chickenpox can cause prolonged discomfort and is associated with infrequent but serious complications. METHODS To evaluate the effectiveness of acyclovir for the treatment of chickenpox, we conducted a multicenter, double-blind, placebo-controlled study involving 815 healthy children 2 to 12 years old who contracted chickenpox. Treatment with acyclovir was begun within the first 24 hours of rash and was administered by the oral route in a dose of 20 mg per kilogram of body weight four times daily for five days. RESULTS The children treated with acyclovir had fewer varicella lesions than those given placebo (mean number, 294 vs 347; P less than 0.001), and a smaller proportion of them had more than 500 lesions (21 percent, as compared with 38 percent with placebo; P less than 0.001). In over 95 percent of the recipients of acyclovir no new lesions formed after day 3, whereas new lesions were forming in 20 percent of the placebo recipients on day 6 or later. The recipients of acyclovir also had accelerated progression to the crusted and healed stages, less itching, and fewer residual lesions after 28 days. In the children treated with acyclovir the duration of fever and constitutional symptoms was limited to three to four days, whereas in 20 percent of the children given placebo illness lasted more than four days. There was no significant difference between groups in the distribution of 11 disease complications (10 bacterial skin infections and 1 case of transient cerebellar ataxia). Acyclovir was well tolerated, and there was no significant difference between groups in the titers of antibodies against varicella-zoster virus. CONCLUSIONS Acyclovir is a safe treatment that reduces the duration and severity of chickenpox in normal children when therapy is initiated during the first 24 hours of rash. Whether treatment with acyclovir can reduce the rare, serious complications of chickenpox remains uncertain.

Acute Suppurative Otitis Media in Children Diversity of Clinical Diagnostic Criteria

Practicing pediatricians were surveyed via mailed questionnaire and a review was made of the pertinent literature in an attempt to identify suitable criteria for making the clinical diagnosis of acute suppurative otitis media (ASOM) in children. Clinical diagnostic criteria were described in only 26 of the 43 studies reviewed; 18 different sets of criteria were used. Use of identical criteria in more than one study was usually the result of multiple publications by particular authors rather than agreement between two investigators. One hundred and sixty-five questionnaire respondents proposed 147 different sets of criteria. Only 11 criteria sets were proposed by more than one respondent, and no single set was listed by more than six respondents. Greater standardiza tion of clinical diagnosis is desirable, but difficult to achieve and will require additional studies to correlate clinical findings with objective measures of diagnosis, such as tympanocentesis.

Explanation for false-positive urine cultures obtained by bag technique.

OBJECTIVE To test whether a urine bag technique, previously shown in circumcised male infants 1 month to 1 year of age to yield no false-positive cultures, would give similar results in newborns (females and circumcised and uncircumcised males). DESIGN Prospective study in which periurethral and urine specimens were obtained from healthy newborns. After the periurethral specimen was obtained, the perineum was washed and a urine bag applied. The urine bag was removed immediately after voiding and the urine was cultured. SETTING Normal newborn nursery and pediatric hospital. SUBJECTS Ninety-eight healthy full-term newborns (49 female and 49 male) admitted to the normal nursery during a 4-month period. MAIN RESULTS Isolation of a pathogen from the bag urine reflected periurethral flora. In 20 (95%) of the 21 urine specimens from which a pathogen was isolated, the same pathogen was detected on the periurethra. Sixteen of the 21 urine cultures were falsely positive (> 10(4) colony-forming units of pathogen per milliliter). In 50 (98%) of the 52 urine samples that yielded no growth, the periurethral culture was also negative. In the remaining 25 urine samples in which nonpathogens were detected, the periurethra yielded nonpathogens or no growth. Thus, if a pathogen was isolated from a bag urine sample, the same pathogen was detected on the periurethra 95% of the time. Conversely, if the bag urine sample was negative for a pathogen, the periurethral culture was negative 100% of the time. The presence of a pathogen on the periurethra was more common in female than male neonates (16 of 49 vs four of 49; P = .004), and none of the 14 circumcised male neonates had a pathogen detected on their periurethra or in their urine. CONCLUSION This study explains the finding of false-positive cultures with the bag technique. Pathogens detected in bag urine samples reflected pathogens on the periurethra. Until a bag collection technique that avoids contamination by periurethral flora can be developed, urethral catheterization and suprapubic aspiration remain the methods of choice for obtaining a urine specimen in female and uncircumcised male neonates.

Three-day therapy of lower urinary tract infectionswith nitrofurantoin macrocrystals: A randomized clinical trial

Forty-nine girls between the ages of 2 and 18 years with a symptomatic urinary tract infection documented by two clean-catch urine cultures completed a double-blind study comparing the effectiveness of three days versus ten days of nitrofurantoin macrocrystal therapy. Localization of the infection to the lower urinary tract was presumed on the basis of clinical presentation. All patients had sterile urine on day two or three of therapy. In the ten-day group, two of 23 patients (8.7%) experienced a single relapse, and seven patients (30%) had 12 episodes of reinfection during a six-month follow-up. In the three-day group, two of 26 patients (7.7%) had a single relapse, and six patients (23%) had 12 episodes of reinfection. The rates of relapse and reinfection in the compared groups were not statistically significantly different (P greater than 0.05). Three days of treatment with nitrofurantoin macrocrystals is an effective regimen for symptomatic girls presumed to have uncomplicated lower urinary tract infections.

Etiologies and early diagnosis of short stature and growth failure in children and adolescents.

Accurate measurement of height and weight using standardized techniques is a fundamental component of pediatric medical visits. Calculation of height velocity over time enables comparison with standardized growth charts to identify potential deviations from normal. Growth deviations may be expressed as SD from the normal population mean for children of comparable age and sex; children with heights >2 SD below the mean are generally classified as short stature. In a child with suspected impaired growth, a detailed evaluation should be conducted to identify the cause. Such an evaluation may include a combination of personal, family, and social history; physical examination; general and perhaps specialized laboratory evaluations; radiologic examinations; genetic testing; and consultation with a pediatric subspecialist, such as a pediatric endocrinologist. Variants of normal growth include familial short stature, constitutional delay of growth and puberty, and small for gestational age with catch-up growth. Pathological causes of abnormal growth include many systemic diseases and their treatments, growth hormone deficiency, and a series of genetic syndromes, including Noonan syndrome and Turner syndrome. Children with short stature in whom no specific cause is identified may be diagnosed with idiopathic short stature. Early identification of abnormal growth patterns and prompt referral to specialist care offer children with growth failure and/or short stature the greatest chance for appropriate diagnosis, treatment, and improved clinical outcomes.

Risk of congenital abnormality after inadvertent rubella vaccination of pregnant women.

The risk to a fetus after rubella vaccination of its mother is unknown. The Center for Disease Control has compiled information from the pregnancies of 343 women inadvertently given rubella vaccine shortly before or after conception. The pregnancies of 145 women were terminated by therapeutic abortion, and rubella vaccine virus was recovered from the products of conception of nine women, including six of the 28 known to be seronegative to rubella at the time of vaccination. None of the 172 infants carried to term had either clinical or serologic evidence of rubella infection, including 38 infants of women known to be susceptible and 12 additional women estimated to be susceptible at the time of rubella vaccination. On the basis of the binomial distribution, the maximum risk of fetal infection after maternal rubella vaccination is between 5 and 10 per cent. The actual risk is probably less.

Statistical Literacy for Readers of Pediatrics: A Moving Target

OBJECTIVE. Pediatric residents are expected to study research design and statistical methods to enable them to critically appraise the pediatric literature and apply the findings to patient care. However, it is not clear how best to teach these skills or even which statistical concepts are most important. An earlier study demonstrated that the statistical complexity of articles published in Pediatrics increased from 1952 to 1982. The goals of our study were to assess whether this trend has continued and to determine the statistical measures and procedures most commonly encountered in Pediatrics. METHODS. We reviewed the print research articles published in Pediatrics, volume 115, 2005, and recorded the statistical measures and procedures reported in each article to determine how many articles used statistics or statistical procedures and what statistical procedures were encountered most commonly. RESULTS. The proportion of articles that used any inferential statistics increased from 48% in 1982 to 89% in 2005. The mean number of inferential procedures per article increased from 2.5 in 1982 to 3.9 in 2005. The most commonly encountered statistical procedures or measures were descriptive statistics, tests of proportions, measures of risk, logistic regression, t tests, nonparametric tests, analysis of variance, multiple linear regression, sample size and power calculation, and tests of correlation. However, a reader who is familiar with only these concepts can understand the analyses used in only 47% of articles. CONCLUSIONS. Our results confirm a trend toward the use of new and increasingly complex statistical techniques in Pediatrics. Educational efforts might most profitably focus on the principles underlying statistical analysis rather than on specific statistical tests. Authors, reviewers, and journal editors have a greater responsibility for ensuring that statistical procedures are used appropriately, as it may be increasingly unrealistic to expect readers to fully understand the statistical analyses used in journal articles.

Comparison of three topical antimicrobials for acute bacterial conjunctivitis

One hundred fifty-eight patients, 21 years of age or less, presenting with culture-positive (Haemophilus influenzae or Streptococcus pneumoniae) conjunctivitis were treated with trimethoprim-polymyxin B (TP), gentamicin sulfate (GS) or sodium sulfacetamide (SS) ophthalmic solution for 10 days. Clinical response at 3 to 6 days after start of therapy was similar for all test agents: 26 of 55 (47%) patients cured, 25 of 55 (45%) improved for TP; 28 of 57 (49%) cured, 26 of 57 (46%) improved for GS; and 19 of 46 (41%) cured, 22 of 46 (48%) improved for SS. Clinical response at 2 to 7 days after completion of therapy was also similar: 46 of 55 (84%) patients cured, 5 of 55 (9%) improved for TP; 50 of 57 (88%) cured, 5 of 57 (9%) improved for GS; and 41 of 46 (89%) cured, 2 of 46 (4%) improved for SS. Bacteriologic response at 2 to 7 days after completion of therapy was similar for all antimicrobials: 44 of 55 (83%) patients for TP; 39 of 57 (68%) for GS; and 33 of 46 (72%) for SS.

Parents' Conception of Their Use of Over-the-counter Medicines

To explore their hypothetical responses to management of fever or nasal congestion in their children, 109 parents were interviewed in a clinic waiting-room area. Most parents said they would medicate their children in these situations without first consulting a health professional. Parents were more willing to administer a drug product for fever than for nasal congestion, especially to children under 2 years of age. Although most parents selected appropriate medi cations for these situations, many were poorly informed about these drugs and falsely attributed germicidal and decongestant properties to aspirin and Tylenol®. Younger, less educated, indigent parents in lower-status occupations were the least well informed. Pediatricians need to prepare parents for their role as health care providers.

Structured guidelines for the use of influenza vaccine among children with chronic pulmonary disorders

National committees recommend annual influenza vaccination for children ≶ 6 months of age with chronic pulmonary diseases, but several studies have suggested that many high risk children do not receive the vaccine. The purpose of this pilot study was to determine whether the use of structured guidelines for which pulmonary disorders warrant influenza vaccination would increase agreement among physicians on whether specific children should be vaccinated. Hospital records of 73 children with an outpatient appointment during the previous month in the pulmonary, allergy or high risk neonatology clinics were reviewed independently by 4 pediatricians. Two reviewers used a set of specific guidelines in deciding whether influenza vaccination was indicated, whereas the other 2 used unspecified clinical judgment. Interrater agreement concerning the advisability of vaccination was higher between the reviewers using the guidelines (overall agreement, 0.89; kappa = 0.73) than between the reviewers using clinical judgment (overall agreement, 0.68; kappa = 0.31). Even among the 34 children for whom all 4 reviewers thought the vaccine advisable, only 13 (38%) had been vaccinated. Studies to define the risk of severe influenza among children with specific lung disorders are needed, but these guidelines can serve as a starting point for the identification of children who deserve individual consideration for annual influenza vaccination.