Sleep Outcomes in Children With Single-Suture Craniosynostosis Compared With Unaffected Controls.

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.

Inflammatory Markers and the Risk of Hip and Vertebral Fractures in Men: the Osteoporotic Fractures in Men (MrOS).

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.

Incident Psychosis in Subjects With Mild Cognitive Impairment or Alzheimer's Disease.

OBJECTIVE: To estimate the incidence of psychotic symptoms in Alzheimer's disease. METHODS: 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. RESULTS: 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%). CONCLUSIONS: 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.

Determinants of patient preferences for total knee replacement: African-Americans and whites.

INTRODUCTION: 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. METHODS: 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). RESULTS: 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 4(th) vs. 1(st) quartile) and WHs (OR 5.11, 95 % CI 2.31-11.30 for 4(th) vs. 1(st) 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 4(th) vs. 1(st) 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. CONCLUSIONS: 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.

Race, sex, and total knee replacement consideration: role of social support.

OBJECTIVE: To determine whether there are racial differences in social support among patients with knee osteoarthritis (OA) and whether the impact of social support on patient preferences for total knee replacement (TKR) varies by race and sex. METHODS: A total of 514 white and 285 African American patients with knee OA were surveyed. Logistic regression models were performed to determine if the relationship between willingness to undergo TKR and the interaction of patient race and sex was mediated by social support. RESULTS: Compared to whites with knee OA, African American patients were less likely to be married (P < 0.001), reported less close friends/relatives (P < 0.001), and had lower Medical Outcomes Study Social Support Scale (MOS-SSS) scores (P < 0.001). African American patients were also less willing to undergo TKR (62% versus 80%; P < 0.001) than whites. The odds of willingness to undergo TKR were less in white females compared to white males when adjusted for recruitment site, age, income, and the Western Ontario and McMaster Universities Osteoarthritis Index score (odds ratio [OR] 0.57, 95% confidence interval [95% CI] 0.34-0.96). This difference was no longer significant when further adjusted for marital status, number of close friends/relatives, and MOS-SSS score, but the effect size remained unchanged (OR 0.60, 95% CI 0.35-1.02). The odds of willingness to undergo TKR remained much less in African American females (OR 0.35, 95% CI 0.19-0.64) and African American males (OR 0.28, 95% CI 0.14-0.54) compared to white males when controlled for sociodemographic, clinical, and social support measures. CONCLUSION: African American patients reported less structural and functional social support than whites. Social support is an important determinant of preference for TKR surgery only among whites.

Psychosocial outcomes in children with and without non-syndromic craniosynostosis: findings from two studies.

Objective : To evaluate the hypothesis that children with craniosynostosis and their parents have differences in psychosocial outcomes, as compared with an unaffected control group. Design : Two studies were conducted, both which followed children born with and without craniosynostosis. Study 1 ascertained affected children from clinics, and study 2 ascertained affected children from a population-based study of birth defects. Participants : Study 1 included 22 children with single-suture craniosynostosis and 18 controls, ages 4 to 5 years. Study 2 included 24 children with nonsyndromic craniosynostosis and 124 unaffected controls, ages 5 to 9 years. Main Outcome Measures : Outcome measures included the Child Behavior Checklist, Social Competence Scale, Pediatric Quality of Life Inventory, and Parenting Stress Index. Results : We observed lower scores on measures of health-related quality of life in cases versus controls, with adjusted effect sizes ranging from -0.72 to -0.44 (p < .05) on summary measures. Small but statistically nonsignificant increases in behavioral problems were observed in cases versus controls, with no apparent differences in social competence or parenting stress. Conclusions : Results provide preliminary evidence suggesting that children with nonsyndromic craniosynostosis may have elevated risk for psychosocial difficulties, particularly health-related quality of life. Continued follow-up through preadolescence and adolescence is warranted.

Plasma follistatin-like protein 1 is elevated in Kawasaki disease and may predict coronary artery aneurysm formation.

OBJECTIVE: To determine whether plasma levels of follistatin-like protein 1 (FSTL-1), a pro-inflammatory protein produced by mesenchymal tissue, including cardiac myocytes, correlate with the development of Kawasaki disease (KD) and coronary artery aneurysms (CAA). STUDY DESIGN: FSTL-1 plasma levels were measured serially with enzyme-linked immunosorbent assay in 48 patients with KD at time of diagnosis and, when available, 2 weeks, 6 weeks, and 6 months after onset of disease. These were compared with FSTL-1 plasma levels in 23 control subjects. Data were analyzed with generalized estimating equations. RESULTS: Plasma FSTL-1 levels were elevated in patients with acute KD compared with control subjects (P = .0086). FSTL-1 levels remained significantly elevated at 2 weeks after disease onset, but returned to control levels by 6 months. Seven patients with CAA had significantly higher FSTL-1 levels at the time of diagnosis than patients in whom aneurysms did not develop (P = .0018). Sensitivity and specificity rates for CAA at a specific FSTL-1 cutoff point (178 ng/mL) were 85% and 71%. CONCLUSIONS: Plasma levels of FSTL-1 are elevated in acute KD and may predict cardiac morbidity in this disease. These results suggest a possible role for FSTL-1 in the formation of CAAs.

Sleep outcomes in children with hemifacial microsomia and controls: a follow-up study.

OBJECTIVE: Children with craniofacial anomalies are at high risk for sleep-disordered breathing (SDB), yet its prevalence among children with craniofacial conditions is not known. Children with hemifacial microsomia (HFM) are likely particularly vulnerable to SDB as a result of underdevelopment of the mandible and oropharynx. Nevertheless, most children with HFM are not referred for sleep studies. We hypothesized that sleep outcomes would be worse in children with HFM versus control subjects. METHODS: We conducted a follow-up study among 124 case participants and 349 control subjects who previously participated in a study of HFM risk factors. Parents completed the Pediatric Sleep Questionnaire (PSQ) regarding symptoms of SDB and sleep habits. Regression models were adjusted for region, age, sex, race/ethnicity, and maternal education. RESULTS: Snoring was more commonly reported for children with HFM (29%) than for control subjects (17%). Compared with control subjects, children with HFM more often had symptoms consistent with SDB. On average, case participants' parents reported 1.9 times as many symptoms on the PSQ breathing scale and 1.3 times more symptoms on the PSQ sleepiness scale than did control subjects' parents, with little difference on the PSQ behavior scale. Parents of children with HFM reported 1.4 times more night awakenings than did control subjects' parents. CONCLUSIONS: Children with HFM experienced more snoring and other symptoms of SDB than did control subjects. Pediatricians should be aware of the increased vulnerability for SDB among children with mandibular or external ear underdevelopment or asymmetry and should refer to a sleep specialist as needed.

Hemifacial microsomia: from gestation to childhood.

Hemifacial microsomia (HFM) is a variable, complex malformation involving asymmetric hypoplasia of the face and ear. Little is known about the risk factors for or consequences of HFM. In this study, we describe 3 studies that have been or are currently being conducted to further our understanding of this malformation. The first completed study examined whether HFM risk is related to maternal exposures that may affect blood flow. In that case-control study, interview data from 230 mothers of children in the case group and 678 mothers of children in the control group suggested that maternal use of vasoactive medications in the first trimester, particularly in combination with cigarette smoking, was associated with increased risks of HFM. The second study is currently underway, in which we are evaluating whether HFM risk is related to genetic variation in pathways associated with vasculogenesis and hemostasis, using DNA collected in the first study. The third ongoing study observes children with HFM to identify psychosocial, cognitive, dental, and medical sequelae. When the children from the original case-control study are 6 or 7 years of age, mothers and teachers complete self-administered questionnaires that cover a wide range of psychosocial development domains. Preliminary analyses of 115 case and 314 control children suggest that children with HFM may have worse teacher-reported academic performance and possibly higher levels of internalizing behavior problems than control children. When data on the full study sample are available, further analyses will determine whether the preliminary findings remain and if they vary by HFM phenotype, parenting style, or indicators of social risk.

Male factor infertility: a twin study.

There is a considerable body of literature on the causes of female infertility, but far less is known about male factor infertility. We conducted a classical twin study to estimate the genetic influence on 12-month male factor infertility. The study used the Vietnam Era Twin (VET) Registry, which includes male twin pairs born between 1939 and 1957, and who served in the US military between 1965 and 1975. In 1987, a health survey was mailed to all twins and obtained a 74% response rate. The current analyses comprised 1795 complete pairs in which both twins were married only once. Proband-wise concordance rates, tetrachoric correlations, and a bivariate probit model were used to calculate estimates of familial clustering and heritability for male factor infertility. The proband concordance rate for male factor infertility was 38% [95% CI 32.8, 42.4] in monozygotic (MZ) pairs and 33% [95% CI 28.0, 38.6] in dizygotic (DZ) pairs. The tetrachoric correlations for male infertility were 0.15 in MZ and 0.04 in DZ pairs. This pattern provides evidence of familial clustering, although genetic influence was not evident (P = 0.21). The current study identified that 12-month male factor infertility clustered within families. However, results suggest that factors unique to individual twins may play a more prominent role in male infertility than additive genetic effects or the common environment.