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Multisystem inflammatory syndrome in children (MIS-C) is an illness that emerged amidst the COVID-19 pandemic but shares many clinical features with the pre-pandemic syndrome of Kawasaki disease (KD). Here we compare the two syndromes using a computational toolbox of two gene signatures that were developed in the context of SARS-CoV-2 infection, i.e., the viral pandemic (ViP) and severe-ViP signatures and a 13-transcript signature previously demonstrated to be diagnostic for KD, and validated our findings in whole blood RNA sequences, serum cytokines, and formalin fixed heart tissues. Results show that KD and MIS-C are on the same continuum of the host immune response as COVID-19. Both the pediatric syndromes converge upon an IL15/IL15RA-centric cytokine storm, suggestive of shared proximal pathways of immunopathogenesis; however, they diverge in other laboratory parameters and cardiac phenotypes. The ViP signatures reveal unique targetable cytokine pathways in MIS-C, place MIS-C farther along in the spectrum in severity compared to KD and pinpoint key clinical (reduced cardiac function) and laboratory (thrombocytopenia and eosinopenia) parameters that can be useful to monitor severity., (© 2022. The Author(s).)

A significant surge in cases of multisystem inflammatory syndrome in children (MIS-C, also called Pediatric Inflammatory Multisystem Syndrome - PIMS) has been observed amidst the COVID-19 pandemic. MIS-C shares many clinical features with Kawasaki disease (KD), although clinical course and outcomes are divergent. We analyzed whole blood RNA sequences, serum cytokines, and formalin fixed heart tissues from these patients using a computational toolbox of two gene signatures, i.e., the 166-gene viral pandemic (ViP) signature, and its 20-gene severe (s)ViP subset that were developed in the context of SARS-CoV-2 infection and a 13-transcript signature previously demonstrated to be diagnostic for KD. Our analyses revealed that KD and MIS-C are on the same continuum of the host immune response as COVID-19. While both the pediatric syndromes converge upon an IL15/IL15RA -centric cytokine storm, suggestive of shared proximal pathways of immunopathogenesis, they diverge in other laboratory parameters and cardiac phenotypes. The ViP signatures also revealed unique targetable cytokine pathways in MIS-C, place MIS-C farther along in the spectrum in severity compared to KD and pinpoint key clinical (reduced cardiac function) and laboratory (thrombocytopenia and eosinopenia) parameters that can be useful to monitor severity.

Background: Newborn screening (NBS) aims to achieve early identification and treatment of affected infants prior to onset of symptoms. The timely completion of each step (i.e., specimen collection, transport, testing, result reporting), is critical for early diagnosis. Goals developed by the Secretary of Health and Human Services' Advisory Committee on Heritable Disorders in Newborns and Children (ACHDNC) for NBS timeliness were adopted (time-critical results reported by five days of life, and non-time-critical results reported by day seven), and implemented into a multi-year quality improvement initiative (NewSTEPS 360) aimed to decrease the time to result reporting and intervention., Methods: The NBS system from specimen collection through reporting of results was assessed (bloodspot specimen collection, specimen shipping, sample testing, and result reporting). Annual data from 25 participating NBS programs were analyzed; the medians (and interquartile range, IQR) of state-specific percent of specimens that met the goal are presented., Results: The percent of specimens collected before 48 hours of life increased from 95% (88-97%) in 2016 to 97% (IQR 92-98%) in 2018 for the 25 states, with 20 (80%) of programs collecting more than 90% of the specimens within 48 hours of birth. Approximately 41% (IQR 29-57%) of specimens were transported within one day of collection. Time-critical result reporting in the first five days of life improved from 49% (IQR 26-74%) in 2016 to 64% (42%-71%) in 2018, and for non-time critical results from 64% (IQR 58%-78%) in 2016 to 81% (IQR 68-91%) in 2018. Laboratories open seven days a week in 2018 reported 95% of time-critical results within five days, compared to those open six days (62%), and five days (45%)., Conclusion: NBS programs that participated in NewSTEPs 360 made great strides in improving timeliness; however, ongoing quality improvement efforts are needed in order to ensure all infants receive a timely diagnosis., Competing Interests: The authors have read the journal's policy and have the following competing interests: MKS, JIM, and YKG are paid employees of CI International. The Cystic Fibrosis Foundation provided support for this study under Grant Number SONTAG16Q10 [MKS]. This does not alter our adherence to PLOS ONE policies on sharing data and materials. There are no patents, products in development or marketed products to declare.

Summary: We describe the case of a 24-year-old male with hyper-IgE syndrome (HIES) which was diagnosed at 4 years of age and died from a very rare cardiac complication. He had typical clinical and laboratory manifestations of HIES, including total serum IgE as high as > 100,000 IU/mL. Stem cell transplantation was not available. During the 20-year follow-up, he suffered numerous various infections of the skin and deep organs, partial lung resection, as well as multiple bone fractures. At age 24, he developed acute decompensated heart failure associated with elevated serum troponin I and brain natriuretic protein. Two-dimensional echocardiogram revealed global hypokinesis of the left ventricle with estimated ejection fraction 20-25%, and catheterization revealed ectasia of multiple coronary arteries. Endomyocardial biopsy showed lymphocytic myocarditis, focal necrosis, mild fibrosis, and myxoid degeneration, but cultures were negative. The patient improved on corticosteroid therapy and was discharged on heart failure therapy and external defibrillator. Six weeks later, he developed supraventricular tachycardia and persistent global hypokinesis and was treated with amiodarone. A trial of intravenous immunoglobulin was initiated and was repeated as outpatient every four weeks for four times. However, his cardiac function did not improve and he developed severe hypotension and pulseless electrical activity arrest. Resuscitation was unsuccessful. To the best of our knowledge, this is the first reported case of HIES complicated with lymphocytic myocarditis. Both immunologists and cardiologists need to be aware of such a complication and practice caution in using immunosuppressants when the patient's immune status is markedly compromised.

Objectives: To determine the level of knowledge of HPV related oropharyngeal cancer and practice patterns of HPV vaccine use by pediatricians., Study Design, Subjects, Methods: IRB approved 18-question survey was administered to members of the Louisiana Chapter of the American Academy of Pediatrics., Results: We received 116 responses (response rate: 15.9 percent );. 104 respondents (89.66 percent ); routinely recommend/offer HPV vaccine, 6 (5.17 percent ); occasionally or only at caregiver request, and 6 (5.17 percent ); do not offer the vaccine. 17 (15.5 percent ); reported having no awareness of the link between oropharyngeal cancer and HPV, and only 50 (45.9 percent ); had knowledge that HPV-related oropharyngeal cancer incidence was increasing. Strength of recommendation for males and knowledge of HPV-related oropharyngeal cancer were not associated with years in practice, practice type or patient population served., Conclusions: Increased awareness regarding HPV-related oropharyngeal cancers among primary care providers may increase HPV immunization rates, especially in males.

Object: Studies have shown decreased levels of nitric oxide (NO), the product of endothelial NO synthase (eNOS) gene activity, in infants with respiratory conditions and intraventricular hemorrhage (IVH). The authors evaluated the association of the eNOS gene promoter polymorphism T-786C with the cause of these conditions (respiratory conditions and IVH) in premature infants., Methods: Blood samples from 124 African American premature infants were studied. The DNA was isolated and microplate polymerase chain reaction-restriction fragment length polymorphism assay was performed. Genotypes were scored as: TT homozygotes with 140 bp and 40 bp; CC homozygotes with 90 bp, 50 bp, and 40 bp; and TC heterozygotes with 140 bp, 90 bp, 50 bp, and 40 bp. Genotypes were stratified according to ethnicity, preterm status, and prematurity conditions., Results: The mutant allele -786C was present in 15.3% of premature infants with respiratory distress syndrome, bronchopulmonary dysplasia, and IVH, compared with 7.25% in those premature infants without these conditions. A significant 2-fold increase of the mutant allele in patients compared with controls (p = 0.04, OR 2.3) reveals that the eNOS -786C allele could be a significant risk factor in the origin of respiratory conditions and IVH in premature infants., Conclusions: These results suggest that the mutant eNOS -786C allele is a significant risk factor in the origin of respiratory and IVH diseases, probably mediating an insufficient supply of endogenous NO in premature infants.

Purpose: IL-13, RANTES (Regulated on Activation, Normal T cells Expressed and Secreted), and cysteinyl leukotrienes are asthma and atopy mediators. Two RANTES -403(G to A) and -28(C to G), an -1055 IL-13(C to T), and a -444(A to C) leukotriene C4 synthase (LTC4S) single nucleotide polymorphisms (SNPs) have been shown in Caucasians and Asians as asthma and atopy risk factors. We studied these SNPs in African Americans with asthma and/or atopy., Methods: We studied 61 patients with asthma and/or atopy and 129 to 157 newborn controls for the -403 RANTES, -28 RANTES, and -1055 IL-13 SNPs, as well as 47 patients and 60 newborn controls for the -444 LTC4S SNP., Results: The two groups did not significantly differ at the genotypes of the -403 and -28 RANTES SNP. On the other hand, the mutant TT genotype for the -1055 IL-13 SNP was detected in 19.7% of patients versus 12.7% in controls (P < 0.04, OR 2.9, 95% CI 1.0-8.0), and the mutant T allele in 58.3% versus 36.6% in controls (P < 0.02, OR 2.4, 95% CI 1.1-5.2). In a similar fashion, for the -444 LTC4S SNP, the mutant AC genotype was detected in 19.1% versus 10.0% in controls (P > 0.28); mutant C allele had an OR of 2.1 (95% CI 0.7-6.3)., Conclusion: African American asthmatics/atopics had higher frequency of the TT mutant gene for the -1055 IL-13 SNP and of its mutant T allele. Regarding the -444 LTC4S SNP, there was a definite difference, although not statistically significant, with an OR of 2.1 for the mutant AC genotype in patients. If these findings become reproduced by larger studies, it may suggest that IL-13 and LTC4S SNPs can be used as predictive markers for asthma/atopy in African Americans.

Sustained-release (SR) bupropion (Zyban) is approved as a smoking cessation aid for adults. Since smoking often begins in adolescence, we determined the single-dose pharmacokinetics of bupropion SR in 75 adolescent subjects ranging from 13 to 18 years old. Subjects self-reported their smoking status. Urinary cotinine concentration was used to verify smoking status. Thirty-seven subjects (18 males, 19 females) were classified as cigarette smokers and 38 were nonsmokers (19 males, 19 females). Fasted subjects received one tablet (150 mg) of bupropion SR, and plasma samples were collected before (0) and 1/2, 1, 2, 3, 4, 6, 8, 24, 48, and 72 hours after dosing. Plasma samples were analyzed for bupropion and its three major metabolites (hydroxybupropion and the aminoalcohol isomers, erythrohydrobupropion plus threohydrobupropion, expressed as a composite) by solid-phase extraction, followed by LC/MS/MS. Factorial analysis of variance (ANOVA) was used to evaluate the effects of smoking and gender on pharmacokinetic parameters. Smokers and nonsmokers differed significantly (p < 0.05) in age and urinary cotinine (p < 0.01) concentration but did not differ significantly in mean weight, height, body surface area, or body mass index. The pharmacokinetic (PK) parameters for bupropion and hydroxybupropion did not differ between smokers and nonsmokers, but differences were found between male and female subjects. Mean values for area under the plasma concentration versus time curve (AUC0-->infinity), volume of distribution (Vd beta) normalized to body weight, maximum plasma concentration (Cmax), and elimination half-life (t1/2 beta) for bupropion were significantly (p < 0.05) greater in females than males, while clearance of bupropion normalized to body weight (CL/f) did not differ between males and females. Females also exhibited significantly (p < 0.05) larger values for hydroxybupropion mean AUC0-->infinity and Cmax than males. The mean ratio of hydroxybupropion to bupropion AUC for adolescents was approximately 4 to 5, which is lower than that previously reported for adults. In conclusion, smoking status does not affect the single-dose pharmacokinetics of bupropion SR in adolescents. However, females differ from males in several potentially important PK parameters for bupropion and its major metabolite, hydroxybupropion.

Unlabelled: Communication about childhood vaccine risks and benefits has been legally required in pediatric health care for over a decade. However, little is known about the actual practice of vaccine risk/benefit communication., Objectives: This study was conducted to identify current practices of childhood vaccine risk/benefit communication in private physician office settings nationally. Specifically, we wanted to determine what written materials were given, by whom, and when; what information providers thought parents wanted/needed to know, the content of nurse and doctor discussion with parents, and the time spent on discussion. We also wanted to quantify barriers to vaccine risk/benefit discussion and to prioritize materials and dissemination methods preferred as solutions to these barriers., Methods: We conducted 32 focus groups in 6 cities, and then administered a 27-question cross-sectional mailed survey from March to September 1998, to a random national sample of physicians and their office nurses who immunize children in private practices. Eligible survey respondents were active fellows of the American Academy of Pediatrics or American Academy of Family Physicians in private practice who immunized children and a nurse from each physician's office. After 3 mailings, the response rate was 71%., Results: Sixty-nine percent of pediatricians and 72% of family physicians self-reported their offices gave parents the Centers for Disease Control and Prevention Vaccine Information Statement, while 62% and 58%, respectively, gave it with every dose. In ~70% of immunization visits, physicians and nurses reported initiating discussion of the following: common side effects, when to call the clinic and the immunization schedule. However, physicians reported rarely initiating discussion regarding contraindications (<50%) and the National Vaccine Injury Compensation Program (<10%). Lack of time was considered the greatest barrier to vaccine risk/benefit communication. Nurses reported spending significantly more time discussing vaccines with parents than pediatricians or family physicians (mean: 3.89 vs 9.20 and 3.08 minutes, respectively). Both physicians and nurses indicated an additional 60 to 90 seconds was needed to optimally discuss immunization with parents under current conditions. Stratified analysis indicated nurses played a vital role in immunization delivery and risk/benefit communication. To improve vaccine risk/benefit communication, 80% of all providers recommended a preimmunization booklet for parents and approximately one half recommended a screening sheet for contraindications and poster for immunization reference. The learning method most highly endorsed by all providers was practical materials (80%). Other desirable learning methods varied significantly by provider type., Conclusions: There was a mismatch between the legal mandate for Vaccine Information Statement distribution and the actual practice in private office settings. The majority of providers reported discussing some aspect of vaccine communication but 40% indicated that they did not mention risks. Legal and professional guidelines for appropriate content and delivery of vaccine communication need to be clarified and to be made easily accessible for busy private practitioners. Efforts to improve risk/benefit communication in private practice should take into consideration the limited time available in an office well-infant visit and should be aimed at both the nurse and physician.

Purpose: To investigate the relationship between inadequate literacy and violent behavior among adolescents., Methods: This descriptive study involved a convenience sample of 386 adolescents who participated in a summer track and field and literacy program serving youths in low-income neighborhoods in Shreveport, Louisiana, during 1994-1996. Self-reported violence was measured using the Youth Risk Behavior Survey (YRBS) and reading grade levels were measured by the Slosson Oral Reading Test-Revised (SORT-R)., Results: Youths ranged in age from 11 to 18 years; 66% were male, and 86% were African-American. Forty-three percent of adolescents tested had below-grade reading levels (> or = 2 grades). Participants with below-grade reading skills had higher rates of self-reported violent behaviors compared with those reading at grade level. When gender, race, and age were controlled for, adolescents reading below grade level were significantly more likely to report carrying weapons [odds ratio (OR) = 1.9; 95% confidence interval (CI) 1.1-3.5], carrying guns (OR = 2.6; CI 1.1- 6.2), to have been in a physical fight at school (OR = 1.7; CI 1.1-2.6), and to have been in a physical fight resulting in injuries requiring treatment (OR = 3.1; CI 1.6-6.1). In addition, youths reading below grade level were significantly more likely to be threatened at school with a weapon (OR = 2.1; CI 1.2-3.7) and to report missing days of school in the previous 30 days because they felt unsafe at school (OR = 2.3; CI 1.3-4.3). In characterizing the violence related behaviors, we found that low reading-level adolescents were more likely to be both aggressor/perpetrator and victim (44% vs. 32%; p = .02) and less likely to be only a victim (6% vs. 12%; p = .04) compared to adolescents with grade-appropriate reading skills., Conclusions: Below-grade-level reading was significantly related to violence behaviors among adolescents who volunteered for a summer track and field program. Longitudinal studies are needed to further investigate the relationship of below-grade-level reading and aggressive/perpetrator and victim behaviors.

Cerebral salt wasting (CSW) is a syndrome of hyponatremia due to excessive natriuresis described in patients with central nervous system insult. We present a 29-month-old black male with tuberculous meningitis who developed CSW with depressed mineralocorticoid activity. The patient required hypertonic saline and ionotropic support. Mineralocorticoid supplementation effectively treated CSW.

Objective: To determine whether vancomycin added to parental nutrition (PN) fluids could prevent nosocomial infections in very low birth weight newborns and which infants would benefit most from prophylaxis., Design: Double blind, randomized controlled study., Setting and Study Population: Very low birth weight infants receiving PN in a tertiary neonatal intensive care unit., Methods: Thirty-eight infants with and without central vascular catheters were randomized to receive no medication or 25 microg/ml vancomycin added to PN for the duration of the infant's PN requirements., Results: The addition of 25 microg/ml vancomycin to PN prevented bacteremia in very low birth weight infants receiving PN. There was a significant reduction in the number of coagulase-negative staphylococcal (CONS) bacteremias (defined as isolation of the same organism from two positive blood cultures) during PN (5 vs. 0; P = 0.037) as well as the total number of bacteremias and fungemias (9 vs. 1; P = 0.036). The total number of hospital days (108 +/- 13 vs. 76 +/- 6; P = 0.039) were reduced in infants receiving vancomycin. Infants with birth weights of < 1000 g who received corticosteroids for treatment of chronic lung disease benefitted most from treatment. No vancomycin-resistant strains of CONS or enterococci were detected during the study period., Conclusions: Prophylactic treatment with vancomycin effectively prevented CONS bacteremia under the conditions of the study. Its use was most effective in infants with birth weights of <1000 g.

This study has examined whether elevated glucose can induce lipid peroxidation and contribute to the inhibition of cell growth in human kidney proximal tubule(HPT) cells. HPT cells were cultured in media containing glucose concentrations of 8 mM (control), 25 mM, and 50 mM. Lipid peroxidation was assessed by the thiobarbituric acid reactivity and cell growth was assessed by 3H-thymidine uptake. Results show decreased (59%, p < 0.01) growth of HPT cells cultured in 50 mM glucose. Cells cultured in 50 mM mannitol did not show any growth inhibition, suggesting that the decreased cell growth associated with glucose is not due to osmolarity changes. There was an increase (108%, p < 0.02) in lipid peroxidation in cells cultured with high levels of glucose (50 mM) compared with controls and cells cultured with 50 mM mannitol. To examine if membrane lipid peroxidation or malondialdehyde (MDA, an end product of lipid peroxidation) has any role in the inhibition of cell growth, we examined the effect of tertiary butylhydroperoxide (TBH, known to cause lipid peroxidation and generate MDA) on the growth of HPT cells. TBH decreased cell growth (49, 17 and 3% of controls at 0.1, 0.25, and 0.5 mumole TBH/ml medium). Similarly, a marked reduction in the growth was observed with exogenous MDA (72, 69 and 34% of controls at 0.1, 0.25, and 0.5 mumole MDA/ml medium). This suggests that elevated glucose can induce membrane lipid peroxidation and accumulation of MDA, which in turn can inhibit cellular growth and contribute to the altered structure and function of HPT cells in diabetes.

Background: Medical information pamphlets often are written using language that requires a reading level higher than parents of many pediatric patients have achieved. Anecdotal reports suggest that many parents may not readily understand the federally mandated Public Health Service vaccine information pamphlets prepared by the Centers for Disease Control and Prevention (CDC) in 1991. The level at which the pamphlets need to be written for low-reading-level parents is undetermined, as is whether parents reading at higher levels will accept low-reading-level materials., Methods: To determine whether a simple pamphlet prepared at a low reading level using qualitative and adult education techniques would be preferable to the available CDC polio vaccine information pamphlet, we conducted an integrated qualitative-quantitative study. We compared the parent reading time and comprehension of a simplified pamphlet (Louisiana State University, LSU) comprising 4 pages, 322 words, 7 instructional graphics, and a text requiring a 6th grade reading ability with the equivalent 1991 CDC vaccine information pamphlet comprising 16 pages, 18,177 words, no graphics, and a text requiring a 10th grade reading level. We measured the reading ability of 522 parents of pediatric patients from northwest Louisiana seen at public clinics (81%) and in a private office (19%). Of the entire group, 39% were white, 60% African-American, and 1% Hispanic; the mean age was 29 years; the mean highest grade completed was 12th grade 3 months; and the reading level was less than 9th grade in 47% of parents and less than 7th grade in 20%. After parents were given one of the pamphlets to read, their reading time, comprehension, and attitude toward the pamphlet were measured., Results: Mean comprehension was 15% lower for CDC than for LSU (56% vs 72% correct; P < .001) and reading time was three times longer for CDC than for LSU (13 minutes 47 seconds vs 4 minutes 20 seconds; P < .0001). These trends were significant for parents reading at all but the lowest levels. Mean comprehension and reading time did not differ among parents reading at the third grade level or less. However, mean comprehension was greater and reading time lower for LSU among parents at all reading abilities greater than the third grade. Parents in the private practice setting took the longest time to read the CDC (20 minutes 59 seconds vs 5 minutes 46 seconds, LSU), yet their comprehension on the LSU was significantly higher than on the CDC (94% vs 71%; P < .0001). Two focus groups of high-income parents were unanimous in preferring the LSU., Conclusions: A short, simply written pamphlet with instructional graphics was preferred by high- and low-income parents seen in private and public clinics. The sixth grade reading level appears to be too high for many parents in public clinics; new materials aimed at third to fourth grade levels may be required. The new 1994 CDC immunization materials, written at the eighth grade level, may still be inappropriately high. The American medical community should adopt available techniques for the development of more effective patient-parent education materials.

Animal studies have shown that maternal protein deficiency during pregnancy affects fetal birth weight. This study has examined whether or not the fetal birth weight of full-term newborns has any relationship with the acute protein nutrition status of the mother. Protein nutrition status was assessed by measuring the plasma transthyretin (prealbumin) concentrations. Plasma transthyretin concentrations (mean +/- SE) from the cord blood of 20 newborns (10.9 +/- 0.5 mg/dl) were significantly lower (p < 0.000000001) compared with respective maternal concentrations (17.8 +/- 0.8). There was a significant correlation of transthyretin concentrations between mother and newborns (r = 0.61, p < 0.005), and of newborn birth weight with plasma transthyretin concentrations of newborns (r = 0.57, p < 0.01) and mothers (r = 0.51, p < 0.03). This study documents a relationship of fetal birth weight with maternal and newborn plasma transthyretin concentrations.

Objectives: To test the reading ability of parents of pediatric outpatients and to compare their reading ability with the ability necessary to read commonly used educational materials; to compare individual reading grade levels with the levels of the last grade completed in school; and to further validate a new literacy screening test designed specifically for medical settings., Design: Prospective survey., Setting: Pediatrics outpatient clinic in a large, public university, teaching hospital., Participants: Three hundred ninety-six parents or other caretakers accompanying pediatric outpatients., Measurements: Demographics and educational status were assessed using a structured interview. Reading ability was tested using the Rapid Estimate of Adult Literacy in Medicine (REALM) and the Wide Range Achievement Test-Revised. Written educational materials were assessed for readability levels with a computer program (Grammatik IV)., Results: The mean score on the REALM for all parents placed them in the seventh to eighth grade reading range, despite the mean self-reported last grade completed in school being 11th grade 5th month. Wide Range Achievement Test-Revised scores correlated well with REALM scores (0.82). Eighty percent of 129 written materials from the American Academy of Pediatrics, the Centers for Disease Control, the March of Dimes, pharmaceutical companies, and commercially available baby books required at least a 10th grade reading level. Only 25% of 60 American Academy of Pediatrics items and 19% of all materials tested were written at less than a ninth grade level, and only 2% of all materials were written at less than a seventh grade level., Conclusion: This study demonstrates that parents' self-reported education level will not accurately indicate their reading ability. Testing is needed to screen at-risk parents for low reading levels. In a public health setting, a significant amount of available parent education materials and instructions require a higher reading level than most parents have achieved. In such settings, all materials probably should be written at less than a high school level if most parents are to be expected to read them. The REALM can easily be used in busy public health clinics to screen parents for reading ability.

Conflicting reports raise a question about decreased plasma clearance (Clp) of theophylline in man during viral infections. Thus a dilemma exists concerning requisite dose adjustments. We examined this issue by retrospectively evaluating theophylline Clp in children infected with respiratory syncytial virus (RSV). Two pharmacokinetic approaches were applied to a one-compartment open model to fit theophylline concentrations during 83 hospitalizations of 76 children, 6 to 48 months of age, who received intravenous theophylline therapy and were tested for RSV infection. Iterative linear regression analyses of all theophylline data were used to estimate apparent volume of distribution, elimination rate constant, plasma half-life, and Clp in 39 of the hospitalizations. When insufficient data were available to distinguish apparent volume of distribution and elimination rate constant (n = 44), steady-state estimates of Clp were calculated. An age-matched and percentile body weight-matched cohort design presented RSV as the primary covariate. Theophylline Clp was similar in 29 matched RSV-infected and -uninfected pairs (1.32 +/- 0.14 and 1.25 +/- 0.05 ml/kg per minute, respectively), as were other pharmacokinetic values. Unexpectedly, a significant, inverse linear relationship was found for Clp and percentile body weight. Additionally, children born prematurely and hospitalized in the neonatal intensive care unit had significantly higher theophylline Clp; this did not affect findings regarding RSV infection. Theophylline Clp was not decreased in RSV-infected children. Current theophylline dosing recommendations for young children infected with RSV should not be altered, but careful monitoring of plasma theophylline levels should be continued.

Respiratory syncytial virus is the major cause of lower respiratory tract infection in children. Adults who are immunocompromised, aged, institutionalized, and/or have underlying medical diseases may be at risk for severe RSV infection. Intubated adults in an MICU were evaluated for evidence of RSV infection. Respiratory secretions were analyzed by cell culture and RSV EIA. Serologic testing was obtained. Respiratory secretions from MICU personnel with acute respiratory symptoms and patients admitted for pneumonia, asthma, or COPD also were screened. Five of 11 intubated patients had evidence of RSV infection. One of seven MICU employees and four of 48 ward patients had RSV-positive respiratory secretions. During community outbreaks of RSV infection, adults admitted to an MICU already may be infected with RSV; those admitted for other reasons are at risk for nosocomial infection. Patients occupying other hospital units and personnel may be instrumental in the nosocomial dissemination of RSV.