bluuebunny/crossref_metadata_2025 huggingface dataset:
Perinatal Correlates of Ureaplasma urealyticum in Placenta Parenchyma of Singleton Pregnancies That End Before 28 Weeks of Gestation
Authors: Olomu I. Nicholas , Hecht Jonathan L. , Onderdonk Andrew O. , Allred Elizabeth N. , Leviton Alan ,   for the Extremely Low Gestational Age Newborn Study Investigators
Published: April 2009

OBJECTIVES. The purpose of this work was to examine the relationship between Ureaplasma urealyticum in the placenta and perinatal outcomes in extreme preterm deliveries and to explore the influence of bacteria coinfection on perinatal outcomes in U urealyticum–positive placentas.

METHODS. Under sterile conditions, a piece of chorion from 866 singleton deliveries before 28 weeks’ gestation was obtained and flash frozen. The tissue was later homogenized and cultured for Ureaplasma and bacteria. Placentas were also examined histologically. Maternal and neonatal data were obtained prospectively. Each infant had 3 sets of cranial ultrasound scans between days 1 to 4, 5 to 14, and between day 15 and 40th week postconceptional age. Cranial ultrasound findings were by consensus of 2 or 2 of 3 sonologists.

RESULTS. U urealyticum was recovered from 6% and bacteria from 47%; 47% of placentas had no bacteria detectable. Sixty-seven percent of Ureaplasma-positive placentas also harbored bacteria. Placentas that harbored U urealyticum only were more likely than sterile placentas to be associated with a higher prevalence of preterm labor and preterm premature rupture of membranes, as well as umbilical cord, fetal vessel, membrane, and parenchymal inflammation and to predict intraventricular hemorrhage and echolucent brain lesions. Placentas that harbored U urealyticum only were similar to placentas that harbored bacteria only. Recovery of U urealyticum and bacteria from same placenta did not enhance the differences between placentas with U urealyticum alone and sterile placentas. Recovery of U urealyticum only was not associated with a higher risk of death before day 7 of life.

CONCLUSIONS. The presence of U urealyticum in placental parenchyma before 28 weeks is associated with increased risk of preterm labor and delivery, higher risk of fetal and maternal inflammation, and increased risk of intraventricular hemorrhage and echolucent brain lesions but not of early neonatal death.
Differential Patterns of 27 Cord Blood Immune Biomarkers Across Gestational Age
Authors: Matoba Nana , Yu Yunxian , Mestan Karen , Pearson Colleen , Ortiz Katherin , Porta Nicolas , Thorsen Poul , Skogstrand Kristin , Hougaard David M. , Zuckerman Barry , Wang Xiaobin
Published: April 2009

OBJECTIVES. Inflammation has been associated with preterm delivery and adverse neonatal outcomes such as cerebral palsy and chronic lung disease. However, no study to date has simultaneously examined a wide range of inflammatory mediators and their relationship to gestational age. We sought to describe the distribution of immune biomarkers in cord blood across gestational age and to investigate the association between biomarker level patterns and preterm birth.

PATIENTS AND METHODS. As part of a large-scale molecular epidemiological study of preterm birth conducted at Boston Medical Center, this study analyzed both clinical and biomarker data from 927 births. Twenty-seven biomarkers were simultaneously quantified by immunoassay. The associations between the quartiles of 27 biomarkers and 3 gestational groups (≤32, 33–36, and ≥37 weeks) were analyzed. Biomarkers found to be significant were further analyzed for dose-response correlation with preterm birth by logistic regression, adjusted for pertinent demographic and clinical factors.

RESULTS. The 27 biomarkers could be classified into 1 of 3 groups: (1) biomarkers increased in preterm birth (interleukin [IL]-2, IL-4, IL-5, IL-8, IL-10, monocyte chemoattractant protein 1, macrophage inflammatory protein [MIP]-1α, MIP-1β, soluble IL-6 receptor α, tumor necrosis factor α, soluble tumor necrosis factor receptor I, and TREM-1 [triggering receptor expressed on myeloid cells 1]); (2) biomarkers decreased in preterm birth (brain-derived neurotrophic factor, IL-1β, IL-18, matrix metalloproteinase 9, and neurotrophin 3); and (3) biomarkers not associated with preterm birth (IL-6, IL-12, IL-17, granulocyte/macrophage colony-stimulating factor, interferon γ, macrophage migration inhibitory factor, neurotrophin 4, RANTES [regulated on activation, normal T-cell expressed and secreted], transforming growth factor β, and tumor necrosis factor β).

CONCLUSIONS. Biomarkers have different directions of association with prematurity; for significant biomarkers, the strength of association increases with biomarker concentration. Our results provide important information that could be used to guide additional studies aimed at determining mechanisms that contribute to preterm birth.
Seven-Year Experience With a Surveillance Program to Reduce Methicillin-Resistant Staphylococcus aureus Colonization in a Neonatal Intensive Care Unit
Authors: Gregory Mary Lucia , Eichenwald Eric C. , Puopolo Karen M.
Published: April 2009

OBJECTIVES. The objectives of this study were to determine the incidence rates of neonatal methicillin-resistant Staphylococcus aureus colonization and infection after the implementation of a NICU methicillin-resistant S aureus surveillance and isolation program and to describe the characteristics of infants with methicillin-resistant S aureus colonization and invasive disease.

METHODS. From August 2000 through August 2007, all infants admitted to the study NICU were screened for methicillin-resistant S aureus colonization with weekly nasal/rectal swabs; colonized or infected infants were isolated and cared for as a cohort. The annual incidence rates of methicillin-resistant S aureus colonization and infection were monitored, and characteristics of methicillin-resistant S aureus-colonized and -infected infants were compared. Data were collected from infant, maternal, and hospital laboratory records.

RESULTS. During the study period, 7997 infants were admitted to the NICU and 102 methicillin-resistant S aureus-colonized or -infected infants (1.3%) were identified. The incidence of methicillin-resistant S aureus decreased progressively from 1.79 cases per 1000 patient-days in 2000 to 0.15 cases per 1000 patient-days in 2005, but the incidence then increased to 1.26 cases per 1000 patient-days in 2007. Fifteen of the 102 case infants (14.7%) had invasive infections; no significant differences between infected and colonized infants were identified. Methicillin-resistant S aureus isolates with 14 different antibiograms were found during the study period. There was a shift from isolates predominantly likely to be hospital-associated in 2000–2004 to those likely to be community-associated in 2006–2007.

CONCLUSIONS. A continuous program of weekly methicillin-resistant S aureus surveillance cultures and isolation of affected infants was associated with a variable incidence of methicillin-resistant S aureus colonization over a 7-year study period. Methicillin-resistant S aureus was not eradicated from this tertiary-care NICU, and our data suggest that infants were colonized by multiple different methicillin-resistant S aureus strains during the study period.
Numbers Needed to Treat With Phototherapy According to American Academy of Pediatrics Guidelines
Authors: Newman Thomas B. , Kuzniewicz Michael W. , Liljestrand Petra , Wi Soora , McCulloch Charles , Escobar Gabriel J.
Published: April 2009

OBJECTIVES. Our aims were to estimate the efficacy of hospital phototherapy for neonatal jaundice and the number needed to treat to prevent one infant from reaching the exchange transfusion level.

METHODS. From a cohort of 281 898 infants weighing ≥2000 g born at ≥35 weeks' gestation at 12 Northern California Kaiser hospitals from 1995 to 2004, we identified 22 547 who had a “qualifying total serum bilirubin level” within 3 mg/dL of the American Academy of Pediatrics 2004 guideline phototherapy threshold. We used multiple logistic regression to estimate the efficacy of hospital phototherapy within 8 hours at preventing the bilirubin level from exceeding the 2004 guideline's exchange transfusion threshold within 48 hours. We combined this efficacy estimate with other predictors of risk to estimate the numbers needed to treat at different values of covariates.

RESULTS. Of the 22 547 eligible newborns, 5251 (23%) received hospital phototherapy within 8 hours of their qualifying bilirubin level. Only 354 (1.6%) ever exceeded the guideline exchange transfusion threshold; 187 (0.8%) did so within 48 hours. Among infants who did not have a positive direct antiglobulin test, hospital phototherapy within 8 hours was highly effective (adjusted odds ratio, 0.16; 95% confidence interval, 0.07–0.34). For infants with bilirubin levels 0–0.9 mg/dL above the phototherapy threshold, the estimated number needed to treat at mean values of covariates was 222 (95% CI: 107–502) for boys and 339 (95% CI: 154–729) for girls, ranging from 10 (95% CI: 6–19) for <24-hour-old, 36-week gestation boys to 3,041 (95% CI: 888–11 096) for ≥3-day-old 41-week girls. Hospital phototherapy was less effective for infants direct antiglobulin test-positive infants (adjusted odds ratio 0.55; 95% CI: 0.21–1.45; P = 0.01 for the direct antiglobulin test × phototherapy interaction).

CONCLUSIONS. While hospital phototherapy is effective, the number needed to treat according to current guidelines varies considerably across different infant subgroups.
Outcomes of Child Sleep Problems Over the School-Transition Period: Australian Population Longitudinal Study
Authors: Quach Jon , Hiscock Harriet , Canterford Louise , Wake Melissa
Published: April 2009

BACKGROUND. Adequate sleep optimizes children's learning and behavior. However, the natural history and impact of sleep problems during school transition is unknown.

OBJECTIVES. To determine (1) the natural history of sleep problems over the 2-year period spanning school entry and (2) associations of children's health-related quality of life, language, behavior, learning, and cognition at ages 6.5 to 7.5 years with (a) timing and (b) severity of sleep problems.

METHODS. Data were drawn from the Longitudinal Study of Australian Children. Children were aged 4 to 5 years at wave 1 and 6 to 7 years at wave 2. Parent-reported predictors included (1) timing (none, persistent, resolved, incident) of moderate/severe sleep problems over the 2 waves and (2) severity (none, mild, moderate/severe) of sleep problems at wave 2. Outcomes included parent-reported health-related quality of life and language, parent- and teacher-reported behavior, teacher-reported learning, and directly assessed nonverbal (matrix reasoning) and verbal (receptive vocabulary) cognition. Linear regression, adjusted for child age, gender, and social demographic variables, was used to quantify associations of outcomes with sleep-problem timing and severity.

RESULTS. Sleep data were available at both waves for 4460 (89.5%) children, of whom 22.6% (17.0% mild, 5.7% moderate/severe) had sleep problems at wave 2. From wave 1, 2.9% persisted and 2.8% developed a moderate/severe problem, whereas 10.1% resolved. Compared with no sleep problems, persistent and incident sleep problems predicted poorest health-related quality of life, behavior, language, and learning scores, whereas resolving problems showed intermediate outcomes. These outcomes also showed a dose-response relationship with severity at wave 2, with effect sizes for moderate/severe sleep problems ranging from −0.25 to −1.04 SDs. Cognitive outcomes were unaffected.

CONCLUSIONS. Sleep problems during school transition are common and associated with poorer child outcomes. Randomized, controlled trials could determine if population-based sleep interventions can reduce the prevalence and impact of sleep problems.
Recognition of a Kawasaki Disease Shock Syndrome
Authors: Kanegaye John T. , Wilder Matthew S. , Molkara Delaram , Frazer Jeffrey R. , Pancheri Joan , Tremoulet Adriana H. , Watson Virginia E. , Best Brookie M. , Burns Jane C.
Published: April 2009

OBJECTIVE. We sought to define the characteristics that distinguish Kawasaki disease shock syndrome from hemodynamically normal Kawasaki disease.

METHODS. We collected data prospectively for all patients with Kawasaki disease who were treated at a single institution during a 4-year period. We defined Kawasaki disease shock syndrome on the basis of systolic hypotension for age, a sustained decrease in systolic blood pressure from baseline of ≥20%, or clinical signs of poor perfusion. We compared clinical and laboratory features, coronary artery measurements, and responses to therapy and analyzed indices of ventricular systolic and diastolic function during acute and convalescent Kawasaki disease.

RESULTS. Of 187 consecutive patients with Kawasaki disease, 13 (7%) met the definition for Kawasaki disease shock syndrome. All received fluid resuscitation, and 7 (54%) required vasoactive infusions. Compared with patients without shock, patients with Kawasaki disease shock syndrome were more often female and had larger proportions of bands, higher C-reactive protein concentrations, and lower hemoglobin concentrations and platelet counts. Evidence of consumptive coagulopathy was common in the Kawasaki disease shock syndrome group. Patients with Kawasaki disease shock syndrome more often had impaired left ventricular systolic function (ejection fraction of <54%: 4 of 13 patients [31%] vs 2 of 86 patients [4%]), mitral regurgitation (5 of 13 patients [39%] vs 2 of 83 patients [2%]), coronary artery abnormalities (8 of 13 patients [62%] vs 20 of 86 patients [23%]), and intravenous immunoglobulin resistance (6 of 13 patients [46%] vs 32 of 174 patients [18%]). Impairment of ventricular relaxation and compliance persisted among patients with Kawasaki disease shock syndrome after the resolution of other hemodynamic disturbances.

CONCLUSIONS. Kawasaki disease shock syndrome is associated with more-severe laboratory markers of inflammation and greater risk of coronary artery abnormalities, mitral regurgitation, and prolonged myocardial dysfunction. These patients may be resistant to immunoglobulin therapy and require additional antiinflammatory treatment.
Maternal Smoking During Pregnancy and Neonatal Behavior: A Large-Scale Community Study
Authors: Stroud Laura R. , Paster Rachel L. , Goodwin Matthew S. , Shenassa Edmond , Buka Stephen , Niaura Raymond , Rosenblith Judy F. , Lipsitt Lewis P.
Published: April 2009

OBJECTIVE. To investigate the influence of prospectively measured smoking during pregnancy on aspects of neonatal behavior in a large community sample.

METHODS. Participants were mothers and infants from the Providence, Rhode Island, cohort of the National Collaborative Perinatal Project enrolled between 1960 and 1966. Mothers with pregnancy/medical complications and infants with medical complications and/or born premature or of low birth weight were excluded. The final sample included 962 mother-infant pairs, 23% of whom were black. Maternal smoking was measured prospectively at each prenatal visit. Neonatal behavior was assessed by using the Graham-Rosenblith Behavioral Examination of the Neonate. Items from the examination were reduced to 3 subscales: irritability, muscle tone, and response to respiratory challenge.

RESULTS. Sixty-two percent of the sample reported smoking during pregnancy, with 24% of smokers reporting smoking 1 pack per day or more. We found a significant influence of maternal smoking exposure (none, moderate/less than 1 pack per day, heavy/1 pack per day or more) on irritability and muscle tone in the neonate, with exposed infants showing greater irritability and hypertonicity. Effects remained significant after controlling for significant covariates: maternal socioeconomic status, age, and race and infant birth weight and age. Posthoc tests suggested particular effects of heavy smoking on increased infant irritability and both moderate and heavy smoking exposure on increased muscle tone.

CONCLUSIONS. In a large community sample, exposure to maternal smoking was associated with increased irritability and hypertonicity in neonates. Exposure to maternal smoking did not influence neonatal response to respiratory challenge. This study is the largest-scale investigation to date of the effects of maternal smoking (heavy and moderate) on examiner-assessed neonatal behavior. Given the associations between both maternal smoking and infant irritability and later behavioral dysregulation, results have important implications for early identification and intervention with at-risk offspring.
Long-term Outcomes of Restorative Proctocolectomy in Children With Ulcerative Colitis
Authors: Pakarinen Mikko P. , Natunen Johanna , Ashorn Merja , Koivusalo Antti , Turunen Pieta , Rintala Risto J. , Kolho Kaija-Leena
Published: April 2009

OBJECTIVE. Long-term outcomes of restorative proctocolectomy for pediatric-onset ulcerative colitis are unclear.

METHODS. Questionnaires on health outcomes and quality of life were mailed to patients with childhood-onset ulcerative colitis who had undergone proctocolectomy with ileoanal anastomosis in 2 university hospitals between 1985 and 2005. Investigators not involved in the surgical management of the patients approached participants. Matched control children were randomly chosen from the Population Register Centre of Finland.

RESULTS. Fifty-two (66%) patients and 117 (37%) controls responded. After a mean follow-up of 10 years, at least 1 surgical complication had occurred in 39 (75%) patients, and 28 (54%) had undergone reoperation. Only 1 failure of ileoanal anastomosis occurred. Ulcerative colitis had been reclassified as Crohn disease in 6 (12%) patients. Pouchitis occurred in 37 (73%) patients. The median stool frequency was 5 for day and 1 for night, but 46% used medication to control stool frequency. Nighttime soiling was reported by 56% of the patients. The mean overall quality-of-life score, the mean BMI (22 kg/m2 for both), and the number of subjects (aged >20 years) with offspring (14% vs 15%) was similar to the population-based controls.

CONCLUSIONS. Stool frequency after restorative proctocolectomy in children with ulcerative colitis is stable and comparable to those of adult patients. Although nighttime incontinence is common, general health status and overall quality of life are comparable to the normal population.
A Cluster of Children With Seizures Caused by Camphor Poisoning
Authors: Khine Hnin , Weiss Don , Graber Nathan , Hoffman Robert S. , Esteban-Cruciani Nora , Avner Jeffrey R.
Published: April 2009

BACKGROUND. Isolated cases of camphor-induced seizures have been reported in young children after gastrointestinal, dermal, and inhalation exposure. In 1982, after a series of unintentional ingestions of camphor products, the US Food and Drug Administration restricted the camphor content to <11% in some products intended for medicinal use. Camphor products intended for use as pesticides must be registered with the US Environmental Protection Agency. Still, many imported camphor-containing products fail to meet Food and Drug Administration and Environmental Protection Agency requirements for labeling and content.

OBJECTIVE. To describe a cluster of cases of camphor-associated seizure activity resulting from the availability of imported camphor products in certain ethnic populations that use it as a natural remedy.

METHODS. We present 3 cases of seizures associated with imported, illegally sold camphor in young children who presented to a large, urban children's hospital in Bronx, New York, during a 2-week period.

RESULTS. The children's ages ranged from 15 to 36 months. Two children ingested camphor, and 1 child was exposed through repetitive rubbing of camphor on her skin. All 3 patients required pharmacologic intervention to terminate the seizures. One patient required bag-valve-mask ventilation for transient respiratory depression. All 3 patients had leukocytosis, and 2 patients had hyperglycemia. Exposure occurred as a result of using camphor for spiritual purposes, cold remedy, or pest control. After identification of these cases, the New York City Department of Health released a public health warning to keep camphor products away from children. Similar warnings were issued later by other state health departments.

CONCLUSIONS. These cases highlight the toxicity associated with camphor usage in the community and that inappropriate use of illegally sold camphor products is an important public health issue. Camphor may be a common, yet unrecognized, source of seizures in children in certain ethnic populations that use it as a natural remedy. Efforts are needed to educate the communities about the hazards of using camphor products and to limit the illegal availability of these products.
The Forgotten Learning Disability: Epidemiology of Written-Language Disorder in a Population-Based Birth Cohort (1976–1982), Rochester, Minnesota
Authors: Katusic Slavica K. , Colligan Robert C. , Weaver Amy L. , Barbaresi William J.
Published: April 2009

OBJECTIVE. The aim of this study was to report the incidence rates and other epidemiologic characterizations of written-language disorder. There have been no epidemiologic studies on the incidence of written-language disorder in the United States, and the use of a population-based birth cohort, longitudinally followed, is the most powerful method for reaching this objective.

METHODS. In this population-based, retrospective birth cohort study, subjects included 5718 children born between 1976 and 1982 in Rochester, Minnesota, who remained in the community after 5 years of age. Records from all public and nonpublic schools, medical facilities, and private tutorial services were reviewed and results of all individually administered IQ and achievement tests, and extensive medical, educational, and socioeconomic information, were collected. The essential features of writing problems from the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision were included in our operationalized definition of written-language disorder. Written-language disorder incident cases were established by using research criteria based on 3 formulas (regression-based discrepancy, nonregression-based discrepancy, and low achievement).

RESULTS. Cumulative incidence rates of written-language disorder varied from 6.9% to 14.7% depending on the formula. Boys were 2 to 3 times more likely to be affected than girls regardless of the formula. Among all written-language disorder cases (N = 806), 25% (n = 203) had written-language disorder without a reading disability. Specifics of the writing problems were identified for 87% (n = 702) of written-language disorder cases.

CONCLUSIONS. In this population-based birth cohort of school-aged children, written-language disorder was at least as frequent as reading disabilities and significantly more frequent among boys than girls.
Treatment of Staphylococcus aureus Colonization in Atopic Dermatitis Decreases Disease Severity
Authors: Huang Jennifer T. , Abrams Melissa , Tlougan Brook , Rademaker Alfred , Paller Amy S.
Published: April 2009

OBJECTIVES. The goals were to determine the prevalence of community-acquired methicillin-resistant Staphylococcus aureus colonization in patients with atopic dermatitis and to determine whether suppression of S aureus growth with sodium hypochlorite (bleach) baths and intranasal mupirocin treatment improves eczema severity.

METHODS. A randomized, investigator-blinded, placebo-controlled study was conducted with 31 patients, 6 months to 17 years of age, with moderate to severe atopic dermatitis and clinical signs of secondary bacterial infections. All patients received orally administered cephalexin for 14 days and were assigned randomly to receive intranasal mupirocin ointment treatment and sodium hypochlorite (bleach) baths (treatment arm) or intranasal petrolatum ointment treatment and plain water baths (placebo arm) for 3 months. The primary outcome measure was the Eczema Area and Severity Index score.

RESULTS. The prevalence of community-acquired methicillin-resistant S aureus in our study (7.4% of our S aureus–positive skin cultures and 4% of our S aureus–positive nasal cultures) was much lower than that in the general population with cultures at Children's Memorial Hospital (75%–85%). Patients in the group that received both the dilute bleach baths and intranasal mupirocin treatment showed significantly greater mean reductions from baseline in Eczema Area and Severity Index scores, compared with the placebo group, at the 1-month and 3-month visits. The mean Eczema Area and Severity Index scores for the head and neck did not decrease for patients in the treatment group, whereas scores for other body sites (submerged in the dilute bleach baths) decreased at 1 and 3 months, in comparison with placebo-treated patients.

CONCLUSIONS. Chronic use of dilute bleach baths with intermittent intranasal application of mupirocin ointment decreased the clinical severity of atopic dermatitis in patients with clinical signs of secondary bacterial infections. Patients with atopic dermatitis do not seem to have increased susceptibility to infection or colonization with resistant strains of S aureus.
Pediatricians' Perceptions of and Preferred Timing for Pediatric Palliative Care
Authors: Thompson Lindsay A. , Knapp Caprice , Madden Vanessa , Shenkman Elizabeth
Published: April 2009

OBJECTIVES. This study investigates how pediatricians define palliative care and their preferences regarding the timing of referrals for children with life-limiting diseases.

METHODS. A random sample of 800 pediatricians in Florida and California received mail and online surveys. Analyses included descriptive and multivariate regression analyses.

RESULTS. Of all respondents (N = 303), 49.1% were female, 34.0% had been practicing for ≥20 years, 44.2% were members of a racial/ethnic minority, and 76.2% were in private practice. Pediatricians were divided in their definitions of palliative care; 41.9% defined it as hospice care, 31.9% offered alternative definitions, and 26.2% did not know. Although pediatricians overwhelmingly cited the need for many types of palliative care services, only 49.3% had ever referred patients to palliative care and 29.4% did not know whether local services existed. For 13 diseases that vary in life limitation, there was no consensus regarding the timing of referrals. Diversity across diseases predicted the most variation in referrals, whereas pediatrician characteristics did not.

CONCLUSIONS. Despite recommendations to refer children to palliative care early in the course of illness, most pediatricians define palliative care as similar to hospice care and refer patients once curative therapy is no longer an option. Creating a more-practical definition of care, one that emphasizes an array of services throughout the course of an illness, as opposed to hospice care, may increase earlier palliative care referrals for children with life-limiting illnesses.
Controlled Clinical Trial of Zolpidem for the Treatment of Insomnia Associated With Attention-Deficit/ Hyperactivity Disorder in Children 6 to 17 Years of Age
Authors: Blumer Jeffrey L. , Findling Robert L. , Shih Weichung Joe , Soubrane Christina , Reed Michael D.
Published: April 2009

OBJECTIVE. The goal was to evaluate the hypnotic efficacy of zolpidem at 0.25 mg/kg per day (maximum of 10 mg/day), compared with placebo, in children 6 through 17 years of age who were experiencing insomnia associated with attention-deficit/hyperactivity disorder.

METHODS. An 8-week, North American, multicenter, double-blind, placebo-controlled, parallel-group study was conducted. Patients underwent stratification according to age (6–11 years [N = 111] or 12–17 years [N = 90]) and were assigned randomly to receive treatment with the study drug or placebo (in a 2:1 ratio). The primary efficacy variable was latency to persistent sleep between weeks 3 and 6. Secondary efficacy variables also were assessed, and behavioral and cognitive components of attention-deficit/hyperactivity disorder were monitored. Safety was assessed on the basis of reports of adverse events, abnormal laboratory data, vital signs, and physical examination findings. The potential for next-day residual effects also was assessed.

RESULTS. The baseline-adjusted mean change in latency to persistent sleep at week 4 did not differ significantly between the zolpidem and placebo groups (−20.28 vs −21.27 minutes). However, differences favoring zolpidem were observed for the older age group in Clinical Global Impression scores at weeks 4 and 8. No next-day residual effects of treatment were associated with zolpidem, and no rebound phenomena occurred after treatment discontinuation. Central nervous system and psychiatric disorders were the most-frequent treatment-emergent adverse events (>5%) that were observed more frequently with zolpidem than with placebo; these included dizziness, headache, and hallucinations. Ten (7.4%) patients discontinued zolpidem treatment because of adverse events.

CONCLUSION. Zolpidem at a dose of 0.25 mg/kg per day to a maximum of 10 mg failed to reduce the latency to persistent sleep on polysomnographic recordings after 4 weeks of treatment in children and adolescents 6 through 17 years of age who had attention-deficit/hyperactivity disorder-associated insomnia.
Validity of Reported Varicella History as a Marker for Varicella Zoster Virus Immunity Among Unvaccinated Children, Adolescents, and Young Adults in the Post–Vaccine Licensure Era
Authors: Perella Dana , Fiks Alexander G. , Jumaan Aisha , Robinson Donovan , Gargiullo Paul , Pletcher Jonathan , Forke Christine M. , Schmid D. Scott , Renwick Mia , Mankodi Foram , Watson Barbara , Spain C. Victor
Published: April 2009

OBJECTIVES. We assessed the validity of reported varicella history as a marker for varicella zoster virus immunity among unvaccinated persons 1 to 29 years of age, and we examined varicella disease characteristics associated with varicella zoster virus immunity among those reporting positive histories.

METHODS. We conducted a cross-sectional study at 7 community-based sites in Philadelphia, Pennsylvania, between June 2004 and May 2006 and recruited 1476 participants 1 to 29 years of age who had not been vaccinated against varicella. Sensitivity, specificity, and positive predictive value were determined by comparing self-reported or parent-reported varicella histories from a standardized study interview with varicella zoster virus immunoglobulin G serological results for each participant. We performed multivariate logistic regression analyses to determine which disease characteristics best predicted seropositivity.

RESULTS. The sensitivity of reported varicella history was highest (81%–89%) among participants ≥10 years of age, whereas specificity was highest among participants 1 to 4 years of age (99%) and ≥20 years (88%). Reported varicella history was highly predictive of seropositivity (>95%) only among participants ≥15 years of age. For participants 10 to 14 years of age, parental reports of a generalized itchy rash with 1 of the following were highly predictive of seropositivity: varicella transmission to another household member or being raised in a household with no other children. Among participants ≤9 years of age, no combination of disease characteristics was both highly predictive of seropositivity and common.

CONCLUSIONS. The validity of reported varicella history varies according to age, and a reported history is no longer highly predictive of seropositivity among cohorts born since 1994 (participants ≤9 years of age). Universal varicella vaccination, regardless of history, for these children should be considered, as should simplified criteria for varicella zoster virus immunity among unvaccinated persons born before 1994.
Abusive Head Trauma in Infants and Children
Authors: Christian Cindy W. , Block Robert ,   and the Committee on Child Abuse and Neglect
Published: April 2009

Shaken baby syndrome is a term often used by physicians and the public to describe abusive head trauma inflicted on infants and young children. Although the term is well known and has been used for a number of decades, advances in the understanding of the mechanisms and clinical spectrum of injury associated with abusive head trauma compel us to modify our terminology to keep pace with our understanding of pathologic mechanisms. Although shaking an infant has the potential to cause neurologic injury, blunt impact or a combination of shaking and blunt impact cause injury as well. Spinal cord injury and secondary hypoxic ischemic injury can contribute to poor outcomes of victims. The use of broad medical terminology that is inclusive of all mechanisms of injury, including shaking, is required. The American Academy of Pediatrics recommends that pediatricians develop skills in the recognition of signs and symptoms of abusive head injury, including those caused by both shaking and blunt impact, consult with pediatric subspecialists when necessary, and embrace a less mechanistic term, abusive head trauma, when describing an inflicted injury to the head and its contents.
Safe Transportation of Preterm and Low Birth Weight Infants at Hospital Discharge
Authors: Bull Marilyn J. , Engle William A. ,   The Committee on Injury, Violence, and Poison Prevention and the Committee on Fetus and Newborn
Published: April 2009

This Policy Statement was reaffirmed August 2013 and June 2018.

Safe transportation of preterm and low birth weight infants requires special considerations. Both physiologic immaturity and low birth weight must be taken into account to properly position such infants. This clinical report provides guidelines for pediatricians and other caregivers who counsel parents of preterm and low birth weight infants about car safety seats.
Spatial Distribution, Energetic Status, and Food Habits of Eastern Bering Sea Age‐0 Walleye Pollock
Authors: Moss Jamal H. , Farley Edward V. , Feldmann Angela M. , Ianelli James N.
Published: April 2009

Age‐0 walleye pollock Theragra chalcogramma were collected from the eastern Bering Sea during years when ocean temperatures were anomalously warm (2004‐2005) and cool (2006‐2007). Variability in spatial distribution, food habits, energetic condition, and recruitment to the age‐1 life stage was investigated in relation to thermal regime. Age‐0 walleye pollock were large in size and widely distributed during warm years, whereas they were small and largely confined to the middle domain of the eastern Bering Sea during cool years. Energy density was positively correlated with body weight and was greater during years when conditions were anomalously cool. The proportion of smaller age‐0 walleye pollock in the diet of larger individuals was high when conditions were warm (21.9% of diet by weight), and euphausiids were the most important prey (36.5% of diet by weight) when conditions were cool. Eastern Bering Sea age‐0 walleye pollock were abundant and broadly distributed from Bristol Bay to offshore and northern locations during warm years; during cool years, age‐0 fish were less abundant and their distribution was constricted to the southeastern Bering Sea. An inverse relationship between brood year abundance and survival from age 0 to age 1 was found. Our results indicate that when spring (summer) sea temperatures on the eastern Bering Sea shelf are very warm and when the water column is highly stratified during summer, age‐0 walleye pollock allocate more energy to growth than to lipid storage, leading to low energy density before winter and thus to higher overwinter mortality.
Electrocardiographic Effects of Lofexidine and Methadone Coadministration: Secondary Findings from a Safety Study
Authors: Schmittner John , Schroeder Jennifer R. , Epstein David H. , Krantz Mori J. , Eid Nicole C. , Preston Kenzie L.
Published: April 2009

Study Objective.To determine the electrocardiographic effects of coadministration of lofexidine and methadone.

Design.Prospective, double‐blind study.

Setting.Outpatient drug treatment research clinic.

Participants.Fourteen adults (mean ± SD age 34.9 ± 5.3 yrs) with physical dependence on opioids.

Intervention.Participants were stabilized on methadone maintenance therapy, reaching a target dose of 80 mg/day. After 3 weeks of methadone stabilization, participants received lofexidine 0.4 mg or placebo once/day, each for 1 week, administered at the same time as methadone. From weeks 3–8, all subjects received lofexidine, with the dose escalated each week in 0.2‐mg increments so that by week 8, participants were receiving lofexidine 1.6 mg/day. Electrocardiograms (ECGs) were obtained at baseline (before methadone), after stabilization with methadone, and after lofexidine coadministration during peak plasma lofexidine levels.

Measurements and Main Results.Prespecified outcome measures of mean and maximal changes in heart rate, and PR, QRS, and QTc intervals were obtained after stabilization with methadone and after lofexidine 0.4 mg coadministration. Repeated‐measures regression showed no significant changes in heart rate or PR, QRS, or QTc interval after methadone stabilization, but a significant decrease in heart rate (mean ± SD −8.0 ± 7.3 beats/min, p=0.0006) after starting lofexidine. When data were analyzed by using maximal ECG response, again, no significant changes were noted during methadone induction compared with baseline, but significant changes did occur in all four ECG parameters when lofexidine was coadministered: decreased heart rate (mean ± SD −9.6 ± 5.8 beats/min, p<0.0001) and increased PR interval (+11.1 ± 19.8 msec, p=0.026), QRS interval (+3.7 ± 4.3 msec, p=0.002), and QTc interval (+21.9 ± 40.8 msec, p=0.018). In three female participants, the change in QTc interval from baseline was clinically significant (> 40 msec).

Conclusion.Our preliminary data suggest that coadministration of lofexidine and methadone induces QTc interval prolongation. This drug combination should be prescribed cautiously, with ECG monitoring. Furthermore, because the participants with the largest changes in QTc interval in our study were female, women may be at highest risk.
Ceftobiprole: First Cephalosporin with Activity Against Methicillin‐Resistant Staphylococcus aureus
Authors: Vidaillac Céline , Rybak Michael J.
Published: April 2009

Ceftobiprole medocaril is the first member of a new series of advanced cephalosporins with activity against methicillin‐resistant Staphylococcus aureus (MRSA). The drug received an approvable letter from the United States Food and Drug Administration (FDA) in March 2008 and from Health Canada in June 2008 for the treatment of complicated skin and skin structure infections including diabetic foot infections. Ceftobiprole exerts its antibacterial activity by inhibiting the penicillin‐binding proteins (PBPs) involved in cell wall synthesis. It has an established stability against hydrolysis by many gram‐positive β‐lactamases and a higher affinity for various PBPs (such as PBP2a of MRSA or PBP2x of Streptococcus pneumoniae), which leads to a wider spectrum of activity compared with older β‐lactams. Ceftobiprole activity does not cover extended‐spectrum β‐lactamase‐producing Enterobacteriaceae and some other pathogens, including Enterococcus faecium or Acinetobacter baumanii. Generally well tolerated, with nausea and taste disturbance being the most common adverse events, ceftobiprole appeared noninferior to empiric therapy in several clinical trials. Ceftobiprole is available only for intravenous administration; recommended dosage regimens have not been approved by the FDA as of this writing. However, based on the Canadian package insert, expected dosage recommendations are 500 mg as a 1‐hour intravenous infusion every 12 hours for the treatment of complicated skin and skin structure infections caused by certain gram‐positive pathogens, and 500 mg as a 2‐hour infusion every 8 hours when susceptible gram‐negative or both gram‐positive and susceptible gram‐negative pathogens are involved. Dosage adjustments are indicated for patients with moderate or severe renal impairment, and dosage recommendations are expected to be 500 or 250 mg, respectively, as a 2‐hour infusion every 12 hours. Several precautions regarding hypersensitivity and drug incompatibility are reported. Ceftobiprole represents a promising option for the treatment of mono‐ and polymicrobial infections caused by multidrug‐resistant gram‐positive and susceptible gram‐negative pathogens, but further toxicity and safety studies are warranted.
Comparison of Sevelamer Hydrochloride and Sevelamer Carbonate: Risk of Metabolic Acidosis and Clinical Implications
Authors: Pai Ashwini B. , Shepler Brian M.
Published: April 2009

Hyperphosphatemia is highly prevalent in patients with chronic kidney disease (CKD), particularly in those with advanced or end‐stage renal disease. Sevelamer hydrochloride is an ion‐exchange resin that reduces serum phosphorus concentrations. The agent also produces favorable lipid profile effects and does not cause hypercalcemia. However, reported drawbacks of this agent are metabolic acidosis, high pill burden, and a relatively low affinity and selectivity for phosphate anions. Sevelamer carbonate is a new buffered formulation that does not increase the risk of metabolic acidosis. To determine the roles of these two agents in the treatment of hyperphosphatemia in patients with CKD, we performed a MEDLINE search (June 1995‐June 2008) focusing on the mechanism of action of resin binding with phosphate and the development of metabolic acidosis. We also reviewed studies that evaluated the effects of sevelamer hydrochloride or sevelamer carbonate on serum bicarbonate concentrations. Several studies in patients with CKD and hyperphosphatemia who received hemodialysis or peritoneal dialysis found decreases in serum bicarbonate concentrations with the use of sevelamer hydrochloride, whereas sevelamer carbonate did not have this negative effect on bicarbonate concentrations. Both drugs appear to be equivalent in their abilities to lower serum phosphorus concentrations. However, as sevelamer carbonate does not decrease serum bicarbonate levels, it may be more appropriate for patients at risk for metabolic acidosis who require phosphate binders that do not contain calcium or aluminum.
Antimicrobial Dosing Concepts and Recommendations for Critically Ill Adult Patients Receiving Continuous Renal Replacement Therapy or Intermittent Hemodialysis
Authors: Heintz Brett H. , Matzke Gary R. , Dager William E.
Published: April 2009

Infectious diseases and impaired renal function often occur in critically ill patients, and delaying the start of appropriate empiric antimicrobial therapy or starting inappropriate therapy has been associated with poor outcomes. Our primary objective was to critically review and discuss the influence of chronic kidney disease (CKD) and acute kidney injury (AKI) on the clinical pharmacokinetic and pharmacodynamic properties of antimicrobial agents. The effect of continuous renal replacement therapies (CRRTs) and intermittent hemodialysis (IHD) on drug disposition in these two populations was also evaluated. Finally, proposed dosing strategies for selected antimicrobials in critically ill adult patients as well as those receiving CRRT or IHD have been compiled. We conducted a PubMed search (January 1980‐March 2008) to identify all English‐language literature published in which dosing recommendations were proposed for antimicrobials commonly used in critically ill patients, including those receiving CRRT or IHD. All pertinent reviews, selected studies, and associated references were evaluated to ensure their relevance. Forty antimicrobial, antifungal, and antiviral agents commonly used in critically ill patients were included for review. Dosage recommendations were synthesized from the 42 reviewed articles and peer‐reviewed, evidence‐based clinical drug databases to generate initial guidance for the determination of antimicrobial dosing strategies for critically ill adults. Because of the evolving process of critical illness, whether in patients with AKI or in those with CKD, prospective adaptation of these initial dosing recommendations to meet the needs of each individual patient will often rely on prospectively collected clinical and laboratory data.
Treatment of Head and Neck Cancers: Issues for Clinical Pharmacists
Authors: Scarpace Sarah L. , Brodzik Frank A. , Mehdi Syed , Belgam Robert
Published: April 2009

Head and neck cancers are a heterogeneous group of diseases involving the oral cavity, pharyngeal tube, and larynx. Given the drug therapy options available, clinical pharmacists can play an important role in the care of this patient population. They can recommend a regimen based on efficacy, toxicity, and patient‐specific factors; ensure that the prescribed regimen has been studied and reported in the literature; verify dosages; and monitor and counsel patients about adverse effects. Chemotherapy plus radiation (chemoradiation) is often the standard treatment for patients with stage III or nonmetastatic stage IV head and neck cancer. Cisplatin‐based regimens are preferred, although carboplatin may be appropriate in some circumstances. Induction therapy with a docetaxel‐based regimen is recommended for some patients; however, this therapy has been associated with a high frequency of grade 3 and 4 neutropenia and febrile neutropenia. Cetuximab, an epidermal growth factor receptor inhibitor, is the newest agent approved for treatment of head and neck cancer. Although evidence supports cetuximab combined with cisplatin versus cisplatin alone for patients with metastatic disease, the role of combination therapy is less clear in patients undergoing chemoradiation. Patients with head and neck cancer may experience swallowing difficulties or mouth pain, possibly interfering with drug administration and adherence; thus, pharmacists in all practice settings should be knowledgeable about different regimens and alternative routes of administration. Xerostomia and mucositis are common adverse effects of radiation therapy, and it is critical that good oral hygiene practices are maintained. Patients may achieve symptomatic relief from xerostomia with saliva substitutes, and clinical experience suggests that use of pilocarpine is worthwhile. Until more evidence becomes available, prevention of xerostomia and mucositis with amifostine is still controversial. Salt‐water rinses, bioadherent oral gel, and honey are relatively inexpensive and nontoxic agents for managing mucositis. Because of the expense of palifermin, it is best reserved for refractory cases. Skin toxicities are common with radiation. Rash is also a common adverse effect of cetuximab. When used together, they may produce complicated skin toxicities. It is important to become familiar with the grading of these rashes so that appropriate therapy can be recommended. As pharmacotherapy for head and neck cancers continues to evolve, clinical pharmacists will continue to have an important role in optimizing treatment for patients by balancing efficacy and toxicity.