Maternal sleep duration and neonate birth weight: A population-based cohort study.

OBJECTIVE: To investigate the association between maternal sleep duration (an important health indicator) and neonate birth weight. METHODS: The study included 2536 mother-neonate pairs of a Spanish birth cohort (2004-2006, INMA project). The exposures were questionnaire-based measures of sleep duration before and during pregnancy. The primary outcome was neonate birth weight score (g) standardized to 40 weeks of gestation. RESULTS: In women sleeping for <7 h/day before pregnancy, each additional hour of sleep increased birth weight score by 44.7 g (P = 0.049) in the minimally adjusted model, although findings were not statistically significant after considering other potential confounders (P > 0.05). However, increasing sleep duration for the group of mothers who slept for more than 9 h/day decreased birth weight score by 39.2 g per additional hour (P = 0.001). Findings were similar after adjusting for several sociodemographic confounders and maternal depression-anxiety clinical history as an intermediate factor. Similar but attenuated associations were observed with sleep duration in the second trimester of pregnancy. CONCLUSION: The relationship between maternal sleep duration before and during pregnancy and neonate birth weight is an inverse U-shaped curve. Excessive sleep duration may adversely affect neonate health through its impact on birth weight.

Corrigendum to "Television viewing duration during childhood and long-association with adolescent neuropsychological outcomes" [Prev. Med. Rep. 4 (2016) 447-452.].

[This corrects the article DOI: 10.1016/j.pmedr.2016.08.013.].

Sativex® as add-on therapy vs. further optimized first-line ANTispastics (SAVANT) in resistant multiple sclerosis spasticity: a double-blind, placebo-controlled randomised clinical trial.

Purpose/aim: To evaluate the efficacy of tetrahydrocannabinol (THC):cannabidiol (CBD) oromucosal spray (Sativex®) as add-on therapy to optimised standard antispasticity treatment in patients with moderate to severe multiple sclerosis (MS) spasticity. METHODS: Sativex® as add-on therapy vs. further optimised first-line ANTispastics (SAVANT) was a two-phase trial. In Phase A, eligible patients received add-on THC:CBD spray for 4 weeks to identify initial responders [≥20% improvement from baseline in spasticity 0-10 numerical rating scale (NRS) score]. Following washout, eligible initial responders were randomised to receive THC:CBD spray or placebo for 12 weeks (double-blinded, Phase B). Optimisation of underlying antispasticity medications was permitted in both groups across all study periods. RESULTS: Of 191 patients who entered Phase A, 106 were randomised in Phase B to receive add-on THC:CBD spray (n = 53) or placebo (n = 53). The proportion of clinically relevant responders after 12 weeks (≥30% NRS improvement; primary efficacy endpoint) was significantly greater with THC:CBD spray than placebo (77.4 vs. 32.1%; p < 0.0001). Compared with placebo, THC:CBD spray also significantly improved key secondary endpoints: changes in mean spasticity NRS (p < 0.0001), mean pain NRS (p = 0.0013), and mean modified Ashworth's scale (p = 0.0007) scores from Phase B baseline to week 12. Adverse events, when present, were mild/moderate and without new safety concerns. CONCLUSIONS: Add-on THC:CBD oromucosal spray provided better and clinically relevant improvement of resistant MS spasticity compared with adjusting first-line antispasticity medication alone.

Television viewing duration during childhood and long- association with adolescent neuropsychological outcomes.

This study is aiming to evaluate the association between television viewing during childhood and long-term adolescent neuropsychological outcomes and the potential explanatory pathways. This is a longitudinal study based on 278 children participating in the INMA birth cohort (1998) in Menorca Island, Spain. The exposure is parent-reported duration of child television viewing (hours per week) at 6 and 9 years of age. Neuropsychological outcomes were assessed at 14 years of age using the N-back test. Behavioral outcomes at 14 years of age were assessed using the Strengths and Difficulties Questionnaire (SDQ) and school performance was assessed by the global school score. Regression models were developed to quantify the associations between duration of television viewing and neuropsychological outcomes adjusted for child and parents' characteristics. The average of weekly TV viewing from 6 to 9 years was 9.2 h (SD: 4.1). Only N-back test outcomes exhibited statistically significant differences in crude models. Children viewing > 14 h per week tended to show larger latencies in working memory reaction time (HRT in ms), beta (CI) = 53 (0-107). After adjusting for potential social confounders, the association weakened and became non-significant but adverse trends were slightly preserved. Early life TV viewing was not associated with adolescent neuropsychological outcomes after adjustment for potential confounders. Further research including larger and exhaustive population-based cohort studies is required in order to verify our conclusions.

Heritability and Genome-Wide Association Analyses of Sleep Duration in Children: The EAGLE Consortium.

STUDY OBJECTIVES: Low or excessive sleep duration has been associated with multiple outcomes, but the biology behind these associations remains elusive. Specifically, genetic studies in children are scarce. In this study, we aimed to: (1) estimate the proportion of genetic variance of sleep duration in children attributed to common single nucleotide polymorphisms (SNPs), (2) identify novel SNPs associated with sleep duration in children, and (3) investigate the genetic overlap of sleep duration in children and related metabolic and psychiatric traits. METHODS: We performed a population-based molecular genetic study, using data form the EArly Genetics and Life course Epidemiology (EAGLE) Consortium. 10,554 children of European ancestry were included in the discovery, and 1,250 children in the replication phase. RESULTS: We found evidence of significant but modest SNP heritability of sleep duration in children (SNP h2 0.14, 95% CI [0.05, 0.23]) using the LD score regression method. A novel region at chromosome 11q13.4 (top SNP: rs74506765, P = 2.27e-08) was associated with sleep duration in children, but this was not replicated in independent studies. Nominally significant genetic overlap was only found (rG = 0.23, P = 0.05) between sleep duration in children and type 2 diabetes in adults, supporting the hypothesis of a common pathogenic mechanism. CONCLUSIONS: The significant SNP heritability of sleep duration in children and the suggestive genetic overlap with type 2 diabetes support the search for genetic mechanisms linking sleep duration in children to multiple outcomes in health and disease.

International Genome-Wide Association Study Consortium Identifies Novel Loci Associated With Blood Pressure in Children and Adolescents.

BACKGROUND: Our aim was to identify genetic variants associated with blood pressure (BP) in childhood and adolescence. METHODS AND RESULTS: Genome-wide association study data from participating European ancestry cohorts of the Early Genetics and Lifecourse Epidemiology (EAGLE) Consortium was meta-analyzed across 3 epochs; prepuberty (4-7 years), puberty (8-12 years), and postpuberty (13-20 years). Two novel loci were identified as having genome-wide associations with systolic BP across specific age epochs: rs1563894 (ITGA11, located in active H3K27Ac mark and transcription factor chromatin immunoprecipitation and 5'-C-phosphate-G-3' methylation site) during prepuberty (P=2.86×10(-8)) and rs872256 during puberty (P=8.67×10(-9)). Several single-nucleotide polymorphism clusters were also associated with childhood BP at P<5×10(-3). Using a P value threshold of <5×10(-3), we found some overlap in variants across the different age epochs within our study and between several single-nucleotide polymorphisms in any of the 3 epochs and adult BP-related single-nucleotide polymorphisms. CONCLUSIONS: Our results suggest that genetic determinants of BP act from childhood, develop over the lifecourse, and show some evidence of age-specific effects.

Multinational comprehensive evaluation of the fixation method used in hip replacement: interaction with age in context.

BACKGROUND: Fixation in total hip replacements remains a controversial topic, despite the high level of its success. Data obtained from major orthopaedic registries indicate that there are large differences among preferred fixation and survival results. METHODS: Using a distributed registry data network, primary total hip arthroplasties performed for osteoarthritis from 2001 to 2010 were identified from six national and regional total joint arthroplasty registries. A multivariate meta-analysis was performed using linear mixed models with the primary outcome revision for any reason. Survival probabilities and their standard errors were extracted from each registry for each unique combination of the covariates. Fixation strategies were compared with regard to age group, sex, bearing, and femoral-head diameter. All comparisons were based on the random-effects model and the fixed-effects model. RESULTS: In patients who were seventy-five years of age and older, uncemented fixation had a significantly higher risk of revision (p < 0.001) than hybrid fixation, with a hazard ratio of 1.575 (95% confidence interval, 1.389 to 1.786). We found a similar, if lesser, effect in the intermediate age group of sixty-five to seventy-four years (hazard ratio, 1.16 [95% confidence interval, 1.023 to 1.315]; p = 0.021) and in the younger age group of forty-five to sixty-four years (hazard ratio, 1.205 [95% confidence interval, 1.008 to 1.442]; p = 0.041). There were no significant differences between hybrid and cemented bearings across age groups. CONCLUSIONS: We conclude that cementless fixation should be avoided in older patients (those seventy-five years of age or older), although this evidence is less strong in patients of intermediate and younger ages.

Genome-wide association study of sexual maturation in males and females highlights a role for body mass and menarche loci in male puberty.

Little is known about genes regulating male puberty. Further, while many identified pubertal timing variants associate with age at menarche, a late manifestation of puberty, and body mass, little is known about these variants' relationship to pubertal initiation or tempo. To address these questions, we performed genome-wide association meta-analysis in over 11 000 European samples with data on early pubertal traits, male genital and female breast development, measured by the Tanner scale. We report the first genome-wide significant locus for male sexual development upstream of myocardin-like 2 (MKL2) (P = 8.9 × 10(-9)), a menarche locus tagging a developmental pathway linking earlier puberty with reduced pubertal growth (P = 4.6 × 10(-5)) and short adult stature (p = 7.5 × 10(-6)) in both males and females. Furthermore, our results indicate that a proportion of menarche loci are important for pubertal initiation in both sexes. Consistent with epidemiological correlations between increased prepubertal body mass and earlier pubertal timing in girls, body mass index (BMI)-increasing alleles correlated with earlier breast development. In boys, some BMI-increasing alleles associated with earlier, and others with delayed, sexual development; these genetic results mimic the controversy in epidemiological studies, some of which show opposing correlations between prepubertal BMI and male puberty. Our results contribute to our understanding of the pubertal initiation program in both sexes and indicate that although mechanisms regulating pubertal onset in males and females may largely be shared, the relationship between body mass and pubertal timing in boys may be complex and requires further genetic studies.

Hours of television viewing and sleep duration in children: a multicenter birth cohort study.

IMPORTANCE: This study used longitudinal data to examine potential associations between hours of television viewing and sleep duration in children. OBJECTIVE: To examine the association between hours of television viewing and sleep duration in preschool and school-aged children. DESIGN, SETTING, AND PARTICIPANTS: Longitudinal, multicenter study among birth cohorts in Menorca, Sabadell, and Valencia from the Spanish Infancia y Medio Ambiente (environment and childhood) project. The study sample included 1713 children (468 from Menorca, 560 from Sabadell, and 685 from Valencia). EXPOSURE: Parent-reported child television viewing duration measured in hours per day at 2 and 4 years of age in Sabadell and Valencia and at 6 and 9 years of age in Menorca. MAIN OUTCOMES AND MEASURES: Parent-reported child sleep duration measured in hours per day at 2 and 4 years of age in Sabadell and Valencia and at 6 and 9 years of age in Menorca. RESULTS: In cross-sectional analysis, children with longer periods of television viewing reported at baseline (≥ 1.5 hours per day) had shorter sleep duration. Longitudinally, children with reported increases in television viewing duration over time (from <1.5 to ≥ 1.5 hours per day) had a reduction in sleep duration at follow-up visits. Results were similar when examining television viewing duration as a continuous variable, with each 1 hour per day of increased viewing decreasing sleep duration at follow-up visits (ß = -0.11; 95% CI, -0.18 to -0.05). Associations were similar when television viewing duration was assessed during weekends and after adjusting for potential intermediate factors (child executive function and attention-deficit/hyperactivity disorder symptoms) and confounders (child physical activity level, parental mental health status, maternal IQ, and maternal marital status). CONCLUSIONS AND RELEVANCE: Children spending longer periods watching television had shorter sleep duration. Changes in television viewing duration were inversely associated with changes in sleep duration in longitudinal analysis. Parents should consider avoiding long periods of daily television exposure among preschool and school-aged children.

Genome-wide association and longitudinal analyses reveal genetic loci linking pubertal height growth, pubertal timing and childhood adiposity.

The pubertal height growth spurt is a distinctive feature of childhood growth reflecting both the central onset of puberty and local growth factors. Although little is known about the underlying genetics, growth variability during puberty correlates with adult risks for hormone-dependent cancer and adverse cardiometabolic health. The only gene so far associated with pubertal height growth, LIN28B, pleiotropically influences childhood growth, puberty and cancer progression, pointing to shared underlying mechanisms. To discover genetic loci influencing pubertal height and growth and to place them in context of overall growth and maturation, we performed genome-wide association meta-analyses in 18 737 European samples utilizing longitudinally collected height measurements. We found significant associations (P < 1.67 × 10(-8)) at 10 loci, including LIN28B. Five loci associated with pubertal timing, all impacting multiple aspects of growth. In particular, a novel variant correlated with expression of MAPK3, and associated both with increased prepubertal growth and earlier menarche. Another variant near ADCY3-POMC associated with increased body mass index, reduced pubertal growth and earlier puberty. Whereas epidemiological correlations suggest that early puberty marks a pathway from rapid prepubertal growth to reduced final height and adult obesity, our study shows that individual loci associating with pubertal growth have variable longitudinal growth patterns that may differ from epidemiological observations. Overall, this study uncovers part of the complex genetic architecture linking pubertal height growth, the timing of puberty and childhood obesity and provides new information to pinpoint processes linking these traits.

The economic cost to households of childhood malaria in Papua New Guinea: a focus on intra-country variation.

BACKGROUND: We compare direct and indirect household costs associated with malaria treatment for children<3 years in two provinces of Papua New Guinea. In particular, we explore the role of uncertainty around mean household costs and whether assuming a normal distribution for household costs limits the accuracy of any direct cost comparisons. METHODS: Exit surveys were undertaken at inpatient and outpatient health facilities. In order to handle uncertainty and facilitate comparisons, parametric and non-parametric bootstrap methods were used to estimate direct and indirect costs at the individual data level. The inpatient and outpatient incremental costs from Madang and Maprik health facilities were compared and significant differences between provinces were identified. RESULTS: Differences were noted between provinces for both inpatient and outpatient household costs. Total arithmetic mean costs for an outpatient malaria episode were US$7.54 in Madang and US$9.20 in Maprik. Total mean inpatient malaria episode costs were US$25.20 in Madang and US$14.08 in Maprik. As cost distributions were not normal, non-parametric bootstrap techniques were used for cost comparisons. Total household costs per outpatient episode of malaria were lower, although not significantly, in Maprik than in Madang (incremental cost of US$ -1.67; 95% CI -4.16, 0.31), while total household costs per inpatient episode were significantly higher in Madang than in Maprik (difference of US$11.16; 95% CI 5.47, 25.33). A difference was noted between provinces in the proportion of indirect costs in total household costs for an outpatient visit: 76% in Madang vs 94% in Maprik. The proportion for indirect costs associated with inpatient visits varied less: 63% in Madang vs 68% in Maprik. CONCLUSIONS: Intra-country differences need to be considered in estimating household costs for both outpatient and inpatient malaria treatment. Our findings suggest that it is important to recognize the impact of both direct and indirect costs on individuals' capacity to afford treatment. Certain indirect costs are difficult to measure accurately, particularly respondents' interpretations of their productive versus non-productive time. Despite this, exploring intra-country cost variation can provide important information to health policy makers.

Prognostic importance of the cause of renal failure in patients with cirrhosis.

BACKGROUND & AIMS: The prognostic value of the different causes of renal failure in cirrhosis is not well established. This study investigated the predictive value of the cause of renal failure in cirrhosis. METHODS: Five hundred sixty-two consecutive patients with cirrhosis and renal failure (as defined by serum creatinine > 1.5 mg/dL on 2 successive determinations within 48 hours) hospitalized over a 6-year period in a single institution were included in a prospective study. The cause of renal failure was classified into 4 groups: renal failure associated with bacterial infections, renal failure associated with volume depletion, hepatorenal syndrome (HRS), and parenchymal nephropathy. The primary end point was survival at 3 months. RESULTS: Four hundred sixty-three patients (82.4%) had renal failure that could be classified in 1 of 4 groups. The most frequent was renal failure associated with infections (213 cases; 46%), followed by hypovolemia-associated renal failure (149; 32%), HRS (60; 13%), and parenchymal nephropathy (41; 9%). The remaining patients had a combination of causes or miscellaneous conditions. Prognosis was markedly different according to cause of renal failure, 3-month probability of survival being 73% for parenchymal nephropathy, 46% for hypovolemia-associated renal failure, 31% for renal failure associated with infections, and 15% for HRS (P < .0005). In a multivariate analysis adjusted for potentially confounding variables, cause of renal failure was independently associated with prognosis, together with MELD score, serum sodium, and hepatic encephalopathy at time of diagnosis of renal failure. CONCLUSIONS: A simple classification of patients with cirrhosis according to cause of renal failure is useful in assessment of prognosis and may help in decision making in liver transplantation.

Predictors of response to therapy with terlipressin and albumin in patients with cirrhosis and type 1 hepatorenal syndrome.

UNLABELLED: Terlipressin plus albumin is an effective treatment for type 1 hepatorenal syndrome (HRS), but approximately only half of the patients respond to this therapy. The aim of this study was to assess predictive factors of response to treatment with terlipressin and albumin in patients with type 1 HRS. Thirty-nine patients with cirrhosis and type 1 HRS were treated prospectively with terlipressin and albumin. Demographic, clinical, and laboratory variables obtained before the initiation of treatment as well as changes in arterial pressure during treatment were analyzed for their predictive value. Response to therapy (reduction in serum creatinine <1.5 mg/dL at the end of treatment) was observed in 18 patients (46%) and was associated with an improvement in circulatory function. Independent predictive factors of response to therapy were baseline serum bilirubin and an increase in mean arterial pressure of >or=5 mm Hg at day 3 of treatment. The cutoff level of serum bilirubin that best predicted response to treatment was 10 mg/dL (area under the receiver operating characteristic curve, 0.77; P < 0.0001; sensitivity, 89%; specificity, 61%). Response rates in patients with serum bilirubin <10 mg/dL or >or=10 mg/dL were 67% and 13%, respectively (P = 0.001). Corresponding values in patients with an increase in mean arterial pressure >or=5 mm Hg or <5 mm Hg at day 3 were 73% and 36%, respectively (P = 0.037). CONCLUSION: Serum bilirubin and an early increase in arterial pressure predict response to treatment with terlipressin and albumin in type 1 HRS. Alternative treatment strategies to terlipressin and albumin should be investigated for patients with type 1 HRS and low likelihood of response to vasoconstrictor therapy.