Phenotypes of Chronic Hepatitis B in Children From a Large North American Cohort.

OBJECTIVE: The aim of the study was to define chronic HBV phenotypes in a large, cohort of United States and Canadian children utilizing recently published population-based upper limit of normal alanine aminotransferase levels (ULN ALT), compared with local laboratory ULN; identify relationships with host and viral factors. BACKGROUND: Chronic hepatitis B virus (HBV) infection has been characterized by phases or phenotypes, possibly associated with prognosis and indications for therapy. METHODS: Baseline enrollment data of children in the Hepatitis B Research Network were examined. Phenotype definitions were inactive carrier: HBeAg-negative with low HBV DNA and normal ALT levels; immune-tolerant: HBeAg-positive with high HBV DNA but normal ALT levels; or chronic hepatitis B: HBeAg-positive or -negative with high HBV DNA and abnormal ALT levels. RESULTS: Three hundred seventy-one participants were analyzed of whom 274 were HBeAg-positive (74%). Younger participants were more likely be HBeAg-positive with higher HBV DNA levels. If local laboratory ULN ALT levels were used, 35% were assigned the immune tolerant phenotype, but if updated ULN were applied, only 12% could be so defined, and the remaining 82% would be considered to have chronic hepatitis B. Among HBeAg-negative participants, only 21 (22%) were defined as inactive carriers and 14 (14%) as HBeAg-negative chronic hepatitis B; the majority (61%) had abnormal ALT and low levels of HBV DNA, thus having an indeterminant phenotype. Increasing age was associated with smaller proportions of HBeAg-positive infection. CONCLUSIONS: Among children with chronic HBV infection living in North America, the immune tolerant phenotype is uncommon and HBeAg positivity decreases with age.

Risk of progression from subjective cognitive decline to mild cognitive impairment: The role of study setting.

INTRODUCTION: We compared risk of progression from subjective cognitive decline (SCD) to mild cognitive impairment (MCI) in an academic memory clinic versus a population-based study. METHODS: Older adults presenting at a memory clinic were classified as SCD (n = 113) or as noncomplainers (n = 82). Participants from a population study were classified as SCD (n = 592) and noncomplainers (n = 589) based on a memory complaint score. Annual follow-up performed for a mean of 3 years. RESULTS: The adjusted hazard ratio for SCD was 15.97 (95% confidence interval: 6.08-42.02, P < .001) in the memory clinic versus 1.18 (95% confidence interval: 1.00-1.40, P = .047) in the population study, where reported "worry" about memory further increased SCD-associated risk for MCI. DISCUSSION: SCD is more likely to progress to MCI in a memory clinic than the general population; participants' characteristics vary across settings. Study setting should be considered when evaluating SCD as a risk state for MCI and dementia.

Health-related Quality of Life in Pediatric Patients With Chronic Hepatitis B Living in the United States and Canada.

OBJECTIVES: The aim of the study was to determine whether selected sociodemographic and hepatitis B virus (HBV)-specific clinical factors are associated with health-related quality of life (HRQoL) among pediatric patients chronically infected with HBV. METHODS: Children with chronic HBV enrolled in the Hepatitis B Research Network completed the Child Health Questionnaire at study entry. Caregivers of children 5 to <10 years completed the parent-reported form (CHQ-Parent Report Form); youth 10 to <18 years completed the child-reported CHQ-Child Report Form. We examined univariable associations of the Child Health Questionnaire scores with selected independent variables: sex, adoption status, maternal education, alanine aminotransferase (U/L), aspartate aminotransferase-to-platelet ratio index, and HBV-specific symptom count. RESULTS: A total of 244 participants (83 young children 5-<10 years, 161 youth 10-<18 years) were included, all HBV treatment-naïve. Among young children, increased alanine aminotransferase level was negatively associated with CHQ-Parent Report Form psychosocial summary t score (r = -0.28, P = 0.01). No other subscale comparisons for young children were statistically significant. Among youth, adoption was associated with better physical functioning and general health (P < 0.01). Higher maternal education was associated with better role/functioning-physical and -emotional scores (P < 0.05). Maternal education and adoption status were linked with adoption associated with higher maternal education. Increased symptom count in youth was associated with worse HRQoL in subscales measuring bodily pain, behavior, mental health, and self-esteem (P < 0.01). CONCLUSIONS: Although overall HRQoL is preserved in children with chronic HBV, some sociodemographic and HBV-related clinical factors were associated with impaired HRQoL in our pediatric patients at baseline. Measurement of HRQoL can focus resources on education and psychosocial support in children and families most in need.

Children with Chronic Hepatitis B in the United States and Canada.

OBJECTIVES: To test the hypothesis that children with chronic hepatitis B living in the US and Canada would have international origins and characteristic hepatitis B virus (HBV) genotypes and laboratory profiles. STUDY DESIGN: Clinical characteristics of children enrolled in the Hepatitis B Research Network were collected from 7 US and Canadian centers. RESULTS: Children (n = 343) with an age range of 1.0-17.8 years were enrolled; 78% of the children were Asian, 55% were adopted, and 97% had international origins with either the child or a parent born in 1 of 31 countries. The majority had HBV genotype B (43%) or C (32%), and the remainder had genotype A (5%), D (16%), E (4%), or multiple (<1%). Children with genotype B or C were more likely to be Asian (98% and 96%), more consistently hepatitis B envelope antigen positive (95% and 82%), had higher median HBV DNA levels (8.2 and 8.3 log10 IU/mL), and less frequently had elevated alanine aminotransferase values (43% and 57%) compared with children with other genotypes. The percentage of hepatitis B envelope antigen positivity and of those with HBV DNA ≥6 log10 IU/mL declined with age. CONCLUSIONS: The majority of children in the Hepatitis B Research Network have HBV genotypes that reflect their international origins. Clinical and laboratory data differ substantially by patient age and HBV genotype. Use of these data can help drive the development of optimal strategies to manage and treat children with chronic hepatitis B.

Association of self-reported nasal blockage with sleep-disordered breathing and excessive daytime sleepiness in Pakistani employed adults.

PURPOSE: To assess prevalence of self-reported nasal congestion and its association with sleep-disordered breathing (SDB) and excessive daytime sleepiness (EDS) in Pakistani adults employed at a medical university. METHODS: All full-time employees of a medical university (n=3,470) were delivered a questionnaire that elicited demographic data, symptoms of nasal blockage and SDB and Epworth Sleepiness Scale score. Overnight pulse oximetry was performed on self-reported snorers and a random sample of non-snorers. Supervised polysomnography was performed on subjects with oxygen desaturation index >5/h. Logistic regression analysis was used to assess the association of nasal blockage with SDB and EDS. RESULTS: Of 2,497 (72%) responders, 45.2% reported nasal congestion. Self-reported nasal blockage was significantly associated with an increased risk of SDB symptoms: snoring (odds ratio [OR] 1.9), witnessed apnoea (OR, 2.2) and unrefreshing sleep (OR, 1.7). Those with nasal blockage had higher Epworth Sleepiness Scale score (5.5 ± 3.6 vs. 3.9 ± 3.3, p<0.001) compared with those without nasal blockage. Nasal blockage was associated with increased risk of doziness in seven out of eight items of Epworth Sleepiness Scale score. Oxygen desaturation index and apnoea-hypopnoea index were similar between subjects with and without self-reported nasal blockage. CONCLUSION: Self-reported nasal blockage is a common symptom in employed Pakistani adults. Self-reported nasal blockage is significantly associated with symptoms of SDB and EDS but not with respiratory variables on overnight sleep monitoring.

Prevalence and associated risk factors of sleep-disordered breathing symptoms in young and middle-aged Pakistani employed adults.

PURPOSE: The objective of this study was to evaluate the prevalence of self-reported sleep-disordered breathing (SDB symptoms and its associated risk factors in Pakistani employed adults. METHODS: Full-time employees (n = 3470) of a medical university were evaluated. Self-administered questionnaire elicited information about demographic data, symptoms of SDB, smoking and alcohol use, presence of nasal congestion, family history of snoring, and included the Epworth Sleepiness Scale. Prevalence of self-reported snoring and of combined SDB symptoms (snoring plus at least one other SDB symptom) was evaluated. Regression analyses were used to assess risk factors associated with self-reported snoring and combined SDB symptoms. RESULTS: Among the 2,497 (72%) responders, prevalence of self-reported snoring was 32%, and combined SDB symptoms 25%. A higher prevalence of snoring and combined SDB symptoms in male gender diminished with age. In univariate analysis, the odds of snoring was higher with age >or=35 yrs (odds ratio (OR) 2.6, confidence interval (CI) 2.2-3.2), body mass index >or=23 (OR 2.6, CI 2.2-3.1), and collar size above 40 cm (OR 2.7, CI 2.3-3.3). Self-reported nasal blockage (OR 1.9, CI 1.6-2.2) and family history of snoring (OR 2.9, 2.5-3.5) were other risk factors. In logistic regression analysis, significant risk factors for SDB symptoms were age, body mass index, collar size, nasal blockage, and family history of snoring. Male gender, smoking and alcohol were not significant risk factors for SDB symptoms. CONCLUSION: The prevalence of SDB symptoms in Pakistani employed adults was comparable to Western populations. However, male gender and smoking were not significant risk factors for SDB symptoms.

Presurgical and postsurgical assessment of the neurodevelopment of infants with single-suture craniosynostosis: comparison with controls.

OBJECT: Although most infants with single-suture craniosynostosis (SSC) appear to have neurodevelopmental test scores in the average range, SSC has been associated with cognitive and motor delays during infancy. Whether and when surgery improves such deficits are not yet known. The authors aimed to compare the pre- and postsurgical neurodevelopmental status of patients with SSC with those of control infants without craniosynostosis. METHODS: The authors conducted a large, multicenter, longitudinal study of 168 infants with craniosynostosis and 115 controls without synostosis who were of similar age, race, sex, and socioeconomic status. The authors assessed participants by using the Bayley Scales of Infant Development, Second Edition (BSID-II) and the Preschool Language Scale, Third Edition (PLS-3) at enrollment, before patients' intracranial surgery, and when participants were 18 months of age (after surgery for patients). RESULTS: After adjusting for potential confounding factors in linear regression analyses, the authors found a tendency for patients to perform similarly to or slightly worse than controls on neurodevelopmental examinations at both visits. After surgery, the patients' mean scores were 0.6 to three points lower than those of controls on the five BSID-II and PLS-3 scales (p = 0.02-0.07). Compared with controls, patients had 2.3 and 1.9 times the adjusted odds of scoring in the delayed range on either BSID-II scale (Mental Development Index and Psychomotor Development Index) for the first and second visits, respectively (p = 0.001 and p = 0.015, respectively). The patients' mean adjusted test scores were nearly unrelated to the timing of their surgery. CONCLUSIONS: These findings support recommendations for neurodevelopmental screening in infants with SSC. Longer follow-up, as is being conducted with the patients in the present study, will be critical for identifying the potential longer-term correlates of SSC and its surgical correction.

Neurodevelopmental outcomes in children with hemifacial microsomia.

OBJECTIVE: To determine whether preadolescent children with hemifacial microsomia (HFM) have higher risk of neurodevelopmental delays than unaffected control individuals. DESIGN: Case-control follow-up study of neurodevelopment in children with and without HFM. SETTING: Case individuals were originally recruited from 26 craniofacial centers across the United States and Canada, and controls were recruited through community pediatricians. PARTICIPANTS: One hundred thirty-six children with HFM (cases) and 568 unaffected children (controls). Main Exposure  History of HFM. MAIN OUTCOME MEASURES: The Peabody Picture Vocabulary Test-Third Edition, the Beery-Buktenica Developmental Test of Visual Motor Integration-Fifth Edition, and the Academic Competence scales from the Child Behavior Checklist and the Teacher Report Form. RESULTS: Children with HFM scored lower than controls on all measures (effect size = -0.27 to -0.45; P < .001 to P = .008). Compared with controls, cases were 2 to 3 times as likely to score in the at-risk range. Relative to controls, outcomes were worse for male cases and those whose mothers were 25 years or younger at the time of their birth. Cases with HFM plus other malformations had poorer outcomes, as did cases with hearing, vision, or speech impairments. CONCLUSIONS: This is the first study, to our knowledge, to show that children with HFM have poorer neurodevelopmental outcomes than unaffected children, but further study using more detailed assessments is indicated. Clinically, the findings suggest that early neurodevelopmental screening is warranted for all children with HFM.

Memory and response inhibition in young children with single-suture craniosynostosis.

Using two versions of the A-not-B task, memory and response inhibition were assessed in 17- to 24-month-old children with surgically corrected single-suture craniosynostosis (cases) and unaffected children (controls). Children's development and language were initially assessed on average at 6-7 months of age and again at this second visit. Cases and controls performed at equivalent levels on average, with cases performing slightly better than controls on several of the variables measured. However, fewer cases than controls were able to complete the more challenging of the two tasks, which may have predictive significance for later functioning. Children's age and cognitive ability were related to successful performance on the A-not-B task. Among cases, age of cranioplastic surgery was unrelated to performance. Our findings suggest that children with single-suture craniosynostosis show normal development of visual memory and response inhibition in the age range studied here.