Yona Keich Cloonan

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.

Objective: To compare risk for sleep-disordered breathing between children with and without single-suture craniosynostosis. Participants: A total of 184 children with single-suture craniosynostosis and 184 controls. Main Outcome Measures: Parent reported sleep-disordered breathing-related symptoms. Results: Current sleep problems were reported in 19% of patients with single-suture craniosynostosis and 14% of controls (adjusted odds ratio = 1.6; 95% CI, 0.9 to 2.8). Ever having sleep problems was reported in 25% and 23% of cases and controls, respectively (adjusted odds ratio = 1.2; 95% CI, 0.7 to 1.9). Overall, snoring was statistically associated with single-suture craniosynostosis ( P = .01) and was more often reported as 2+ nights per week (versus never) in patients with single-suture craniosynostosis (13%) than in controls (4%) (adjusted odds ratio = 3.5; 95% CI, 1.5 to 8.2). Conclusions: Though preliminary, increased presence of snoring during sleep in children with single-suture craniosynostosis compared with controls suggests that children with isolated single-suture craniosynostosis may be at increased risk for sleep-disordered breathing. Further study using standardized assessments of sleep-disordered breathing is needed.

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 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.

To estimate the incidence of psychotic symptoms in Alzheimer's disease. The study consists of 776 elderly subjects presenting to the Alzheimer Disease Research Center at the University of Pittsburgh (Pittsburgh, Pennsylvania) between May 9, 2000, and August 19, 2014. All participants were diagnosed with mild cognitive impairment (National Institute on Aging-Alzheimer's Association workgroup criteria) or possible or probable Alzheimer's disease (National Institute of Neurologic and Communicative Disorders and Stroke and the Alzheimer's Disease and Related Disorders Association criteria) and were without psychosis at entry. Psychotic symptoms were evaluated using the Consortium to Establish a Registry for Alzheimer's Disease Behavioral Rating Scale every 6 months. One-, 3- and 5-year cumulative incidences of psychosis were calculated. The 1-year psychosis incidence was 10% (95% CI, 8%-12%), and this annual rate remained remarkably consistent at 3 and 5 years. Psychosis incidence was related to cognitive status at all time points. However, the incidence rate reached a plateau during the disease course. Cumulative psychosis incidence at 5 years was 61% (95% CI, 52%-69%) in individuals with moderate to severe Alzheimer's disease, not statistically significantly different from the cumulative incidence at 3 years in this group, which was 48% (95% CI, 40%-55%) or from the 5-year incidence in individuals who entered the study with mild Alzheimer's disease, which was 48% (95% CI, 41%-56%). Psychosis in Alzheimer's disease has been associated with a number of adverse clinical outcomes. We provide estimates of the risk of psychosis onset within clinically defined subgroups of individuals, a tool clinicians can use in treatment planning. Anticipating which subjects are at high risk for psychosis and the poor outcomes associated with it can help with family education and support decisions to implement nonpharmacologic strategies that may reduce or prevent symptoms.

: Cytokines play major roles in regulating bone remodeling, but their relationship to incident fractures in older men is uncertain. We tested the hypothesis that men with higher concentrations of pro-inflammatory markers have a higher risk of fracture. We used a case-cohort design and measured inflammatory markers in a random sample of 961 men and in men with incident fractures including 120 clinical vertebral, 117 hip, and 577 non-spine fractures; average follow-up 6.13 years (7.88 years for vertebral fractures). We measured interleukin (IL)-6, C-reactive protein (CRP), tumor necrosis factor alpha (TNFα), soluble receptors (SR) of IL-6 (IL-6SR) and TNF (TNFαSR1 and TNFαSR2), and IL-10. The risk of non-spine, hip, and clinical vertebral fracture was compared across quartiles (Q) of inflammatory markers using Cox proportional hazard models with tests for linear trend. In multivariable-adjusted models, men with the highest (Q4) TNFa cytokine concentrations and their receptors had a 2.0–4.2-fold higher risk of hip and clinical vertebral fracture than men with the lowest (Q1). Results were similar for all non-spine fractures, but associations were smaller. There was no association between CRP and IL-6SR and fracture. Men in the highest Q of IL-10 had a 49% lower risk of vertebral fracture compared with men in Q1. Among men with ≥3 inflammatory markers in the highest Q, the hazard ratio (HR) for hip fractures was 2.03 (95% confidence interval [CI] 1.11–3.71) and for vertebral fracture 3.06 (1.66–5.63). The HRs for hip fracture were attenuated by 27%, 27%, and 15%, respectively, after adjusting for appendicular lean mass (ALM), disability, and bone density, suggesting mediating roles. ALM also attenuated the HR for vertebral fractures by 10%. There was no association between inflammation and rate of hip BMD loss. We conclude that inflammation may play an important role in the etiology of fractures in older men. © 2016 American Society for Bone and Mineral Research.

Patient preferences contribute to marked racial disparities in the utilization of total knee replacement (TKR). The objectives of this study were to identify the determinants of knee osteoarthritis (OA) patients’ preferences regarding TKR by race and to identify the variables that may mediate racial differences in willingness to undergo TKR. Five hundred fourteen White (WH) and 285 African-American (AA) patients with chronic knee pain and radiographic evidence of OA participated in the study. Participants were recruited from the community, an academic medical center, and a Veterans Affairs hospital. Structured interviews were conducted to collect socio-demographics, disease severity, socio-cultural determinants, and treatment preferences. Logistic regression was performed, stratified by race, to identify determinants of preferences. Clinical and socio-cultural factors were entered simultaneously into the models. Stepwise selection identified factors for inclusion in the final models (p < 0.20). Compared to WHs, AAs were less willing to undergo TKR (80 % vs. 62 %, respectively). Better expectations regarding TKR surgery outcomes determined willingness to undergo surgery in both AAs (odds ratio (OR) 2.08, 95 % confidence interval (CI) 0.91-4.79 for 4th vs. 1st quartile) and WHs (OR 5.11, 95 % CI 2.31-11.30 for 4th vs. 1st quartile). Among AAs, better understanding of the procedure (OR 1.80, 95 % CI 0.97-3.35), perceiving a short hospital course (OR 0.81, 95 % CI 0.58-1.13), and believing in less post-surgical pain (OR 0.73, 95 % CI 0.39-1.35) and walking difficulties (OR 0.66, 95 % CI 0.37-1.16) also determined willingness. Among WHs, having surgical discussion with a physician (OR 1.96, 95 % CI 1.05-3.68), not ever receiving surgical referral (OR 0.56, 95 % CI 0.32-0.99), and higher trust in the healthcare system (OR 1.58, 95 % CI 0.75-3.31 for 4th vs. 1st quartile) additionally determined willingness. Among the variables considered, only knowledge-related matters pertaining to TKR attenuated the racial difference in knee OA patients’ treatment preference. Expectations of surgical outcomes influence preference for TKR in all patients, but clinical and socio-cultural factors exist that shape marked racial differences in preferences for TKR. Interventions to reduce or eliminate racial disparities in the utilization of TKR should consider and target these factors.