Human metapneumovirus infections are associated with severe morbidity in hospitalized children of all ages.

The impact of human metapneumovirus (HMPV) in children aged >5 years and the risk factors associated with disease severity for all ages have not been well characterized. A retrospective cohort study of 238 children aged 0­15 years hospitalized over a 3-year period was performed. Medical records were reviewed for demographic information, clinical parameters and outcomes. Multivariable analyses were performed to identify independent factors associated with worse disease severity assessed by length of hospital stay (LOS), need for ICU care, respiratory support, and a disease severity score. Pulmonary diseases were associated with all outcomes of care, while congenital heart disease (CHD) and neuromuscular disorders were associated with longer LOS, and CHD and trisomy 21 were associated with worse severity scores independent of other covariables. Fever, retractions, use of steroids and albuterol were also associated with enhanced disease severity. Understanding the determinants of HMPV disease in children may help design targeted preventive strategies.

Polymorphisms of the glucocorticoid receptor gene in Graves ophthalmopathy.

BACKGROUND/AIMS: Glucocorticoids have an important role in the regulation of the immune system, and alterations in glucocorticoid signaling may have an impact on the pathophysiology of autoimmune and inflammatory disorders. Because polymorphisms of the glucocorticoid receptor (GR) gene, including the N363S, ER22/23EK, A3669G and BclI variants were found to influence glucocorticoid signalling, we examined whether these polymorphisms could be associated with the development or clinical manifestations of Graves ophthalmopathy (GO). METHODS: The carrier and allelic frequencies of the N363S, ER22/23EK, A3669G, and BclI polymorphisms of the GR were determined in 95 Hungarian outpatients with GO and 160 healthy controls. RESULTS: No significant changes were found in carrier frequencies of the four polymorphisms between GO patients and healthy controls. However, when GO patients were divided into two subgroups (American Thyroid Association Committee, ATA I-II vs ATA III or greater), the frequency of the polymorphic BclI allele was significantly higher in patients with ATA I-II compared with those with ATA III or more (p = 0.009). CONCLUSION: The significant association between the frequency of the polymorphic BclI allele and ATA stage distribution suggests that this polymorphism of the GR gene may affect clinical manifestations of GO, presumably due to an increased signaling of endogenous glucocorticoids.

Gastrostomy tube placement in nonadherent HIV-infected children.

OBJECTIVE: To determine the benefits of gastrostomy tube (G-tube) placement in HIV-infected children receiving highly active antiretroviral therapy (HAART). METHODS: Children who had a G-tube placed due to medication adminsitration difficulties were followed to determine changes in medication adherence and changes in laboratory parameters. Medication adherence and laboratory parameters were reviewed for three months prior to G-tube placement and then were followed for six months after G-tube placement. Viral RNA and CD4+ counts were assessed between the two time periods. Medication adherence was followed by review of pharmacy refill records and pill counts. Parents were surveyed about their opinion regarding the G-tube placement and medication administration in their children. RESULTS: Six children had G-tubes placed due to medication administration difficulties. The G-tube was tolerated in all six cases, although one child developed a staphylococcal infection 13 months after G-tube placement. Before G-tube placement, the medication adherence to HAART averaged 47% +/- 20% SD, with a range of 15-90%. After G-tube placement, medication adherence improved to 90-100%. All parents were satisfied with the G-tube and all reported shorter medication administration times and fewer behavioral problems. Five of six patients had at least a 2-log10 decrease in viral load, and CD4+ percentages improved by an average of 6.4%. CONCLUSIONS: G-tubes were well tolerated by HIV-infected children. Although G-tube placement is not needed in most children with HIV, it may provide an option for parents and children where administration of antiretroviral medication poses extreme difficulty and all other avenues have been exhausted.

The safety and antiviral effect of protease inhibitors in children.

STUDY OBJECTIVE: To determine the safety and antiviral effect of protease inhibitors (PIs) over 36 months in pediatric patients infected with the human immunodeficiency virus (HIV). DESIGN: Observational study SETTING: Pediatric immunodeficiency clinic. PATIENTS: Twenty-one children. INTERVENTION: Demographics, dosage regimens, genotype data, viral RNA and CD4+ lymphocyte counts, adverse drug events (ADEs), laboratory tests, and compliance were evaluated over 3 years. Data were analyzed by chi2, repeated measures analysis of variance, and paired t tests. MEASUREMENTS AND MAIN RESULTS: Twenty-one pediatric patients (aged 3 mo-15 yrs) received PIs over the study period. Average daily doses were ritonavir 26 mg/kg in 12 patients, nelfinavir 94 mg/kg in 16, indinavir 49 mg/kg in 5, and saquinavir 43 mg/kg in 4. Five patients developed resistance to an existing PI. Overall compliance was 70%. Baseline HIV-1 RNA plasma concentrations were significantly higher than average follow-up concentrations during 3-36 months in patients taking ritonavir (p<0.001) and nelfinavir (p<0.001). Sample size was insufficient for indinavir or saquinavir. Sixty ADEs occurred, diarrhea being most common. Of patients with ADEs, 55% required increased monitoring and 43% treatment. Ritonavir was associated with the most ADEs (28), followed by nelfinavir (16), indinavir (11), and saquinavir (5). Significant increases between baseline and follow-up cholesterol levels were found with ritonavir (p=0.02) and nelfinavir (p=0.001), and for serum creatinine (p=0.02) and triglycerides (p=0.02) with ritonavir. Follow-up triglycerides were significantly higher than baseline for indinavir (p=0.003). CONCLUSION: Nelfinavir and ritonavir were effective in decreasing HIV-1 viral loads and improving CD4+ lymphocyte counts. Ritonavir was associated with more ADEs than other PIs. Changes in cholesterol, serum creatinine, and triglycerides were noted with some PIs.

Periorbital cellulitis secondary to Conidiobolus incongruus.

A previously healthy, 18-month-old girl developed edema and erythema around her left eye 1 week after getting sand in that eye. The patient did not respond to oral or intravenous antibiotics. A mass developed around the eye, and biopsy revealed Conidiobolus incongruus. The patient failed to respond to amphotericin B 1 mg/kg, and susceptibility tests indicated multiantifungal resistance. A combination of antifungal therapy, hyperbaric oxygen, and surgery was required for successful treatment. Three months after treatment the child was disease free. There is no definitive therapy for Conidiobolus incongruus infections, although various drugs have been administered with some success. When susceptibility tests determine multidrug resistance, radical resection with antifungal chemotherapy and hyperbaric oxygen may be necessary as well as lifesaving.

Acute hepatitis and bleeding possibly induced by zidovudine and ritonavir in an infant with HIV infection.

Acute hepatitis led to abnormal coagulopathy, bleeding, and death in a nonhemophiliac infant infected with the human immunodeficiency virus, possibly due to zidovudine or ritonavir or both. Acute hepatitis during ritonavir treatment and episodes of spontaneous bleeding have been reported in patients with hemophilia. Zidovudine is associated with elevated liver enzymes, elevated bilirubin, and hepatomegaly leading to abnormal coagulopathy, bleeding, and death in adults. A temporal relationship between the start of combination antiretroviral therapy and onset of hepatosplenomegaly and rise in liver enzymes suggests that zidovudine or ritonavir, or both, are the likely cause of this adverse event. Ritonavir is believed to cause direct hepatotoxicity, probably by inducing acute mitochondrial toxicity, and may hasten reverse transcriptase inhibitor-induced liver toxicity. Liver function of patients receiving a combination of nucleoside reverse transcriptase inhibitor and protease inhibitors should be closely monitored.

Disclosure, stress, and psychological adjustment among mothers affected by HIV.

This study examined patterns of disclosure and psychological adjustment among mothers infected or affected by HIV. All participants were followed through a family AIDS clinic at a midwestern children's hospital. With respect to disclosure, results indicated that high perceived stress (r = 0.50, p = 0.001) and low efficacy related to managing parenting demands (r = -0.42, p = 0.01) were significantly associated with disclosure of seropositive status. Neither time since diagnosis, psychological adjustment, AIDS knowledge, nor health status as indicated by CD4 count were related to disclosure. Results also indicated that 51% of the mothers met DSM-IV diagnostic criteria for a psychological disorder in the preceding year. The most common diagnoses included posttraumatic stress disorder and major depression. Analyses suggested that perceived stress accounted for a significant 43% of the variance in psychological adjustment. Neither disclosure, time since diagnosis, nor CD4 count were related to adjustment. Findings are discussed in terms of mothers' mental health needs and provision of services to families affected by HIV/AIDS. Although the results of this study must be considered preliminary due to a limited number of participants and correlational analyses, they point to several avenues for future research.

Pancreatitis in children infected with human immunodeficiency virus.

The incidence of pancreatitis in HIV-infected children is not well known. Medical records of 42 children with HIV infection followed at Children's Hospital during a 6-year period were reviewed. Pancreatitis (elevated serum lipase levels) developed in 10 children (23.8%). Three children acquired HIV infection from vertical transmission and seven from contaminated blood products (hemophiliacs). Nine were severely immunosuppressed (CD4+ of < 100 cells/mm3). Lipase values were more often elevated than amylase values. The clinical course was protracted and severe in two children, one had four recurrences, and seven had only a single episode of pancreatitis lasting a few weeks. Opportunistic infections were present in four children and seven were receiving medications previously implicated as cause of pancreatitis. Discontinuation of dideoxynosine (ddI) in one child led to rapid resolution of pancreatitis, but continuation of medications in the other children did not alter the course. The etiology of pancreatitis may be multifactorial. Severe and prolonged clinical course is associated with advanced HIV infection. Determination of serum lipase is more useful than serum amylase for identifying those with pancreatitis.

Pharmacokinetics of azithromycin in pediatric patients with acute otitis media.

The objective of our study was to characterize the pharmacokinetics of azithromycin after the oral administration of multiple doses in suspension to children with acute otitis media. Thirteen children (ranging in age from 7.5 months to 5 years) received a single oral dose of 10 mg of azithromycin per kg of body weight on day 1 followed by single daily doses of 5 mg/kg on days 2 to 5. Each child fasted overnight before receiving the final dose on day 5. Multiple blood samples were collected after the last dose. Concentrations of azithromycin in serum were measured by a specific high-performance liquid chromatography-mass spectrometry method. The means and standard deviations for the maximum concentration of azithromycin in serum, the time to maximum concentration of azithromycin in serum, the area under the concentration-time curve (from 0 to 24 h), and the elimination half-life were 224 +/- 120 ng/ml, 1.8 +/- 0.4 h, 1,841 +/- 651 ng.h/ml, and 31.6 +/- 6.6 h, respectively. Concentrations in serum (means +/- standard deviations) at 0 h (predose) and at 24, 48, and 72 h after the final dose were 51 +/- 26, 47 +/- 21, 27 +/- 17, and 17 +/- 13 ng/ml, respectively. Thus, the once-daily administration of azithromycin resulted in sustained systemic exposure to the drug. The drug dosage regimen used in this study should lead to tissue drug concentrations exceeding the MICs for common pathogens.

Pharmacokinetics of azithromycin in pediatric patients after oral administration of multiple doses of suspension.

Azithromycin is an azalide antibiotic. On the basis of data in adults, azithromycin appears to have a greater distribution into tissues, a longer elimination half-life, and a lower incidence of adverse effects than the macrolide antibiotic erythromycin. However, little about the pharmacokinetics of azithromycin in children is known. The objective of our study was to characterize the pharmacokinetics of azithromycin after oral administration of multiple doses of suspension to children with streptococcal pharyngitis. Fourteen children (6 to 15 years of age) received a single oral dose of 10 mg of azithromycin per kg of body weight on day 1 followed by single daily doses of 5 mg/kg on days 2 to 5. Each child fasted overnight before receiving the final dose on day 5. Blood samples were collected at 0, 0.5, 1, 2, 4, 6, 8, 12, 24, 48, and 72 h after this last dose. Concentrations of azithromycin in serum were measured by a specific high-performance liquid chromatography-mass spectrometry method. The mean +/- standard deviation for maximum concentration of drug in serum, time to maximum concentration of drug in serum, and area under the curve (0 to 24 h) were 383 +/- 142 ng/ml, 2.4 +/- 1.1 h, and 3,109 +/- 1,033 ng.h/ml, respectively. Concentrations in serum at 0 h (predose) and at 24, 48, and 72 h after the final dose were 67 +/- 31, 64 +/- 24, 41 +/- 17, and 29 +/- 14 ng/ml, respectively. Thus, once-daily administration of azithromycin resulted in sustained systemic exposure to the drug.

Pharmacokinetics of loracarbef in pediatric patients.

Loracarbef is an investigational oral antibiotic but its pharmacokinetics have not been studied after multiple oral doses in pediatric patients. The pharmacokinetics of loracarbef were determined in 18 pediatric patients after multiple oral doses. 8 patients with streptococcal pharyngitis received 7.5 mg/kg every 12 h, and 10 patients with otitis media were given 15 mg per kg every 12h. Multiple blood and urine samples were collected to measure loracarbef concentrations. In patients with streptococcal pharyngitis, the mean maximum serum concentration (Cmax), the time to achieve maximum concentration (Tmax), area under the serum concentration-time curve (AUC) and elimination half-life (t1/2) were 10.6 +/- 3.6 mcg/ml, 0.78 +/- 0.21 h, 21.4 +/- 7.2 mcg.h/ml, and 1.2 + 0.4 h, respectively. The mean Cmax, Tmax, AUC and t1/2 were 18.0 +/- 5.4 mcg/ml, 0.83 +/- 0.44 h, 35.6 +/- 9.4 mcg.h/ml, and 1.1 +/- 0.5 h, respectively, in patients with otitis media. The Cmax exceeded the minimum inhibitory concentration of common susceptible pathogens causing pharyngitis and otitis media by severalfold. Nearly 60% of the dose was excreted unchanged in the urine during the dosage interval. The pharmacokinetics were independent of dose. Loracarbef was well tolerated in all patients. These data suggest that loracarbef may be used safely at doses of 7.5 mg/kg every 12 h in pediatric patients with streptococcal pharyngitis and 15 mg/kg every 12 h in those with otitis media.

Nursing bottle weaning and prevention of dental caries: a survey of pediatricians.

Numerous studies have documented the cariogenic effects of prolonged or nocturnal bottle feeding in children. Guidelines prepared by the American Academy of Pediatrics (AAP) suggest that pediatricians advise parents to begin bottle weaning when their child is approximately nine months of age and accomplish weaning soon after the first birthday. However, little information exists concerning the advice pediatricians give to parents about nursing bottle weaning. Information about bottle weaning advice was obtained from 127 pediatricians selected from the American Academy of Pediatrics (AAP) Fellowship listing (1985-86). The majority of respondents discussed bottle weaning with parents and recommended a specific age for accomplishment of bottle weaning. Bedtime bottle feeding was discouraged actively, mainly due to the increased risk of dental caries. Implications of the findings are discussed.

Management of pediatric patients with otitis media in the emergency department.

We designed a study to evaluate the pattern and appropriateness of the use of drugs and the laboratory data or procedure in 100 patients (age 1 month-17 years) seen in the emergency department with the diagnosis of otitis media during 178 visits. Patients were selected randomly among those seen during 1983. All patients had usual signs and symptoms of otitis media. Antibiotics prescribed were amoxicillin during 94 visits, trimethoprim/sulfamethoxazole during 33 visits, erythromycin/sulfisoxazole during 14 visits, cefaclor during 5 visits and ampicillin during 3 visits. Due to incomplete dose strength of regimen, only 60% of antibiotic orders were evaluable. The antibiotic doses were within the recommended range in 40% of evaluable cases. Antihistamines and decongestants were used in 28 cases. Analgesics, a variety of ear drops and vinegar irrigation solutions were utilized in 40 cases. Otoscopy was performed in all patients and tympanogram was done in two patients. Ear exudate culture was performed in 5 patients and was found to be positive in 3 cases. All patients were asked to return but only 33 patients came back for a total of 42 follow-up visits to the hospital. Otitis media was reported resolved during 31 visits, resolving during 7 visits, persisting during 3 visits and worsening during 1 visit. The results of this study demonstrate that (1) antibiotic selection was appropriate but the antibiotic orders were incomplete and the doses were frequently out of recommended range; (2) adjunctive drugs seemed to be utilized appropriately; (3) laboratory data and procedures were used appropriately.(ABSTRACT TRUNCATED AT 250 WORDS)