Dynamical properties of the two-process model for sleep-wake cycles in infantile autism

The two-process model is a scheme for the timing of sleep that consists of homeostatic (Process S) and circadian (Process C) variables. The two-process model exhibits abnormal sleep patterns such as internal desynchronization or sleep fragmentation. Early infants with autism often experience sleep difficulties. Large day-by-day changes are found in the sleep onset and waking times in autistic children. Frequent night waking is a prominent property of their sleep. Further, the sleep duration of autistic children is often fragmented. These sleep patterns in infants with autism are not fully understood yet. In the present study, the sleep patterns in autistic children were reproduced by a modified two-process model using nonlinear analysis. A nap term was introduced into the original two-process model to reproduce the sleep patterns in early infants. The nap term and the time course of Process S are mentioned in the present study. Those parameters led to bifurcation of the sleep-wake cycle in the modified two-process model. In a certain range of these parameter sets, a small external noise was amplified, and an irregular sleep-wake cycle appeared. The short duration of sleep led to another irregular sleep onset or waking. Consequently, an irregular sleep-wake cycle appeared in early infantile autism.     

Preventing Obesity during Infancy: A Pilot Study

More than 20% of US children between ages 2 and 5 years are overweight suggesting efforts to prevent obesity must begin earlier. This study tested the independent and combined effects of two behavioral interventions delivered to parents, designed to promote healthy infant growth in the first year. Mother‐newborn dyads intending to breastfeed were recruited from a maternity ward. With a 2 × 2 design, 160 dyads were randomized into one of four treatment cells to receive both, one, or no interventions delivered at two nurse home visits. The first intervention (“Soothe/Sleep”) instructed parents on discriminating between hunger and other sources of infant distress. Soothing strategies were taught to minimize feeding for non‐hunger‐related fussiness and to prolong sleep duration, particularly at night. The second intervention (“Introduction of Solids”) taught parents about hunger and satiety cues, the timing for the introduction of solid foods, and how to overcome infants' initial rejection of healthy foods through repeated exposure. A total of 110 mother‐infant dyads completed the year‐long study. At 1 year, infants who received both interventions had lower weight‐for‐length percentiles (P = 0.009). Participants receiving both interventions had a mean weight‐for‐length in the 33rd percentile; in contrast, those in other study groups were higher first intervention only—50th percentile; second intervention only—56th percentile; control group—50th percentile).This suggests that multicomponent behavioral interventions may have potential for long‐term obesity prevention (ClinicalTrials.gov number, NCT00359242).     

Review and Meta‐analysis of Pharmacotherapy for Binge‐eating Disorder

This study evaluated available controlled treatment studies to determine utility of pharmacotherapy for binge‐eating disorder (BED). The authors identified randomized placebo‐controlled trials testing pharmacotherapy‐only treatments and controlled trials testing pharmacotherapy with psychotherapy treatments. Meta‐analysis was performed on placebo‐controlled trials with data for attrition, remission, and weight loss. Qualitative review was performed on remaining controlled treatment literature. A total of 33 studies were considered of which 14 studies with a total of 1,279 patients were included in the meta‐analysis of pharmacotherapy‐only treatment and 8 studies with a total of 683 patients were included in the qualitative review of pharmacotherapy combined with psychotherapy interventions. No evidence suggested significant differences between medication and placebo for attrition. Evidence suggested that pharmacological treatments have a clinically significant advantage over placebo for achieving short‐term remission from binge eating (48.7% vs. 28.5%) and for weight loss, although weight losses are not substantial. No data exist to allow evaluation of longer‐term effects of pharmacotherapy‐only treatment for BED. Combining medications with psychotherapy interventions failed to significantly enhance binge outcomes, although specific medications (orlistat, topiramate) enhanced weight losses achieved with cognitive behavioral therapy and behavioral weight loss. In summary, BED patients can be advised that certain pharmacotherapies may enhance likelihood of stopping binge eating short term, but that longer‐term effects are unknown. Although some weight loss may occur, it is unlikely to be substantial with available medications. Combining medications with cognitive or behavioral treatments is unlikely to enhance binge outcomes, but specific medications (orlistat, topiramate) may enhance weight losses, albeit modestly.     

Two‐year Follow‐up in 21,784 Overweight Children and Adolescents With Lifestyle Intervention

Although randomized controlled trials demonstrated the long‐term efficacy of lifestyle interventions in overweight children, the effects of these interventions in clinical practice under real‐life conditions are largely unknown. One hundred twenty‐nine centers specialized in outpatient pediatric obesity care participated in this quality assessment. All patients presenting before the year 2006 for lifestyle intervention of at least 6 months duration in these institutions were analyzed in a 2‐year follow‐up. A total of 21,784 (45% male) overweight children and adolescents aged 2–20 years (mean BMI 30.4 kg/m², mean SDS‐BMI 2.51, mean age 12.6 years) were included in the analysis. Based on an intention‐to‐treat analysis with variables set back to baseline in lost of follow‐up, 22% of the children reduced their SDS‐BMI after 6 months, 15% after 12 months, and 7% after 24 months, but only in 24, 17, and 8% of children, respectively, complete data were available. In the five treatment centers with the best outcome (518 patients), 83% of the children reduced their overweight after 6 months, 67% after 12 months, and 51% after 24 months. Under real‐life conditions, most treatment centers cannot prove the long‐term efficacy of their interventions due to high drop‐out rate or lack of documentation. Conversely, some institutions achieved a reduction of overweight in nearly the half of their patients 24 months after baseline demonstrating the great heterogeneity in outcome. To improve the effectiveness of lifestyle interventions in real‐life studying, the process and structure quality as well as their long‐term results is urgently needed.     

Modifiable environmental and behavioral determinants of overweight among children and adolescents: report of a workshop

The number of children at risk for overweight and the number of overweight children are increasing and have become a serious public health concern. Interventions that could be applied at the population level have not been proven effective. The development of effective strategies is thought to be hampered by the lack of understanding of which behavioral and environmental factors need to be modified. On June 14 and 15, 2004, the NIH held a meeting of experts to discuss the issue of modifiable determinants of obesity in children and adolescents. Included were presentations on interventions among children that have been proven effective, dietary and physical activity behavioral determinants, physical, social, and family environmental determinants, and the quality of measures of determinants and correlates of overweight.     

Neurofeedback for Autistic Spectrum Disorder: A Review of the Literature

There is a need for effective interventions to address the core symptoms and problems associated with autistic spectrum disorder (ASD). Behavior therapy improves communication and behavioral functioning. Additional treatment options include psychopharmacological and biomedical interventions. Although these approaches help children with autistic problems, they may be associated with side effects, risks or require ongoing or long-term treatment. Neurofeedback is a noninvasive approach shown to enhance neuroregulation and metabolic function in ASD. We present a review of the literature on the application of Neurofeedback to the multiple problems associated with ASD. Directions for future research are discussed.     

Sleep problems in individuals with 11q terminal deletion disorder (Jacobsen syndrome)

Characteristics of sleep and sleep problems were investigated in 43 individuals with 11q terminal deletion disorder (Jacobsen syndrome). Data were collected using a sleep questionnaire. Ten individuals (23%) had a sleep problem. Settling problems, frequent night waking and early waking occurred in 2 (4%), 7 (16%) and 2 (6%) individuals, respectively. Twenty-two individuals (54%) had a history of sleep problems. Twenty-five individuals (60%) showed restless sleep and 23 individuals (54%) slept in an unusual position. Apart from frequent coughs, no significant relationships were found between the presence of a sleep problem and other variables, such as age, level of ID, breathing problems, heart defects, constipation, daytime activity and behavioral diagnosis, restless sleep and sleeping in an unusual positions.     

Lipid management after acute coronary syndrome

PURPOSE OF REVIEW: Despite advances in medical therapy and percutaneous revascularization, patients with acute coronary syndrome face a high risk of early, recurrent cardiovascular events. Interventions targeting atherogenic lipoproteins may favorably modify this risk. RECENT FINDINGS: Two randomized clinical trials, MIRACL and PROVE-IT, demonstrated efficacy of early, intensive statin therapy after acute coronary syndrome. Recent observational and meta-analyses corroborate the findings of these trials. The benefit of intensive statin treatment appears to apply broadly to elderly as well as younger patients, and to patients with or without diabetes or metabolic syndrome. Randomized trials demonstrating the efficacy of early, intensive statin treatment after acute coronary syndrome employed fixed statin dosages, and there does not appear to be an initial or achieved LDL-cholesterol level below which benefit is absent. As such, broad application of intensive statin therapy after acute coronary syndrome may be preferable to titration of statin dose to achieve specific LDL goals. Low HDL-cholesterol predicts risk after acute coronary syndrome; therefore, pharmacologic interventions to raise HDL concentration or mimic its function may help reduce that risk. SUMMARY: Early, intensive statin therapy is safe and effective after acute coronary syndrome. Future research will determine whether drugs that raise or mimic HDL-cholesterol are effective adjuncts to statin therapy.     

Efficacy and acceptability of pharmacological,psychosocial, and brain stimulation interventions in children and adolescents with mental disorders: an umbrella review

Top‐tier evidence on the safety/tolerability of 80 medications in children/adolescents with mental disorders has recently been reviewed in this jour­nal. To guide clinical practice, such data must be combined with evidence on efficacy and acceptability. Besides medications, psychosocial inter­ventions and brain stimulation techniques are treatment options for children/adolescents with mental disorders. For this umbrella review, we systematically searched network meta‐analyses (NMAs) and meta‐analyses (MAs) of randomized controlled trials (RCTs) evaluating 48 medications, 20 psychosocial interventions, and four brain stimulation techniques in children/adolescents with 52 different mental disorders or groups of mental disorders, reporting on 20 different efficacy/acceptability outcomes. Co‐primary outcomes were disease‐specific symptom reduction and all‐cause discontinuation (“acceptability”). We included 14 NMAs and 90 MAs, reporting on 15 mental disorders or groups of mental disorders. Overall, 21 medications outperformed placebo regarding the co‐primary outcomes, and three psychosocial interventions did so (while seven outperformed waiting list/no treatment). Based on the meta‐analytic evidence, the most convincing efficacy profile emerged for amphetamines, methylphenidate and, to a smaller extent, behavioral therapy in attention‐deficit/hyperactivity disorder; aripiprazole, risperidone and several psychosocial interventions in autism; risperidone and behavioral interventions in disruptive behavior disorders; several antipsychotics in schizophrenia spectrum disorders; fluoxetine, the combination of fluoxetine and cognitive behavioral therapy (CBT), and interpersonal therapy in depression; aripiprazole in mania; fluoxetine and group CBT in anxiety disorders; fluoxetine/selective serotonin reuptake inhibitors, CBT, and behavioral therapy with exposure and response prevention in obsessive‐compulsive disorder; CBT in post‐traumatic stress disorder; imipramine and alarm behavioral intervention in enuresis; behavioral therapy in encopresis; and family therapy in anorexia nervosa. Results from this umbrella review of interventions for mental disorders in children/adolescents provide evidence‐based information for clinical decision making.     

Preventing post-traumatic stress disorder after mass exposure to violence

Bioterrorism preparedness plans must take into account the psychosocial consequences of exposure to mass violence. If possible, post-traumatic stress disorder (PTSD), which is associated with significant morbidity and cost, should be prevented. There are, however, no effective interventions that have been scaled up to prevent PTSD following mass exposure to violence. In fact, randomized controlled trials of the most commonly used preventive intervention, psychological debriefing, suggest no efficacy, or even potential harm. Fortunately, randomized controlled trials of cognitive behavioral therapy--that is, targeting individuals who are symptomatic in the weeks after trauma--reveal significant efficacy. Given the potential for repeated mass violence exposure, public health professionals need to refine methods for screening and tracking large numbers of casualties. At the same time, the use of telephone and internet-based cognitive behavioral therapy protocols should be further tested as strategies for bringing the only effective early intervention for PTSD to scale. Research on preventive pharmacotherapy for PTSD and on the effects of media exposure on PTSD severity is also a priority.     

Internet and Computer-Based Cognitive Behavioral Therapy for Anxiety and Depression in Youth: A Meta-Analysis of Randomized Controlled Outcome Trials

Background

Anxiety and depression in children and adolescents are undertreated. Computer- and Internet-based cognitive behavioral treatments (cCBT) may be an attractive treatment alternative to regular face-to-face treatment.This meta-analysis aims to evaluate whether cCBT is effective for treating symptoms of anxiety and depression in youth.

Methods and Findings

We conducted systematic searches in bibliographical databases (Pubmed, Cochrane controlled trial register, PsychInfo) up to December 4, 2013. Only randomized controlled trials in which a computer-, Internet- or mobile-based cognitive behavioral intervention targeting either depression, anxiety or both in children or adolescents up to the age of 25 were compared to a control condition were selected. We employed a random-effects pooling model in overall effect analyses and a mixed effect model for sub-group analyses. Searches resulted in identifying 13 randomized trials, including 796 children and adolescents that met inclusion criteria. Seven studies were directed at treating anxiety, four studies at depression, and two were of a transdiagnostic nature, targeting both anxiety and depression. The overall mean effect size (Hedges’ g) of cCBT on symptoms of anxiety or depression at post-test was g=0.72 (95% CI:0.55-0.90, numbers needed to be treated (NNT)=2.56). Heterogeneity was low (I²=20.14%, 95% CI: 0-58%). The superiority of cCBT over controls was evident for interventions targeting anxiety (g=0.68; 95% CI: 0.45-0.92; p < .001; NNT=2.70) and for interventions targeting depression (g=0.76; 95% CI: 0.41-0.12; p < .001; NNT=2.44) as well as for transdiagnostic interventions (g=0.94; 95% CI: 0.23-2.66; p < .001; NNT=2.60).

Conclusions

Results provide evidence for the efficacy of cCBT in the treatment of anxiety and depressive symptoms in youth. Hence, such interventions may be a promising treatment alternative when evidence based face-to-face treatment is not feasible. Future studies should examine long-term effects of treatments and should focus on obtaining patient-level data from existing studies, to perform an individual patient data meta-analysis.     

Cell-based therapies for the preterm infant

The severely preterm infant receives a multitude of life-saving interventions, many of which carry risks of serious side effects. Cell therapy is an important and promising arm of regenerative medicine that may address a number of these problems. Most forms of cellular therapy use stem/progenitor cells or stem-like cells, which have the capacity to migrate, engraft and exert anti-inflammatory effects. Although some of these cell-based therapies have made their way to clinical trials in adults, little headway has been made in the neonatal patient group. This review discusses the efficacy of cell therapy in preclinical studies to date and their potential applications to diseases that afflict many prematurely born infants. Specifically, we identify the major hurdles that must be overcome before cell therapies can be safely used in the neonatal intensive care unit.     

The effect of low birth weight on height,weight and behavioral outcomes in the medium-run

A number of studies have documented negative long term effects of low birth weight. Yet, not much is known about the dynamics of the process leading to adverse health and educational outcomes in the long run. While previous studies focusing mainly on LBW effects on physical growth and cognitive outcomes have found effects of the same size at both school age and young adulthood, others have found a diminishing negative effect over time. The purpose of this paper was to bring new evidence to this issue by analyzing the medium run effects of low birth weight on child behavioral outcomes as well as physical growth at ages 6 months, 3½, 7½ and 11 years using data from the Danish Longitudinal Survey of Children. Observing the same children at different points in time enabled us to chart the evolution of anthropometric and behavioral deficits among children born with low birth weight and helped understanding the nature and timing of interventions.     

Respiration During Sleep in Children

In 22 children (11 boys and 11 girls), aged 9 to 13 years, respiration was monitored during one night of sleep. No child had a significant history of breathing problems during sleep. Sleep was recorded using standard techniques (electroencephalography, electrooculography, electromyography), and respiration was measured with nasal thermistors and abdominal or thoracic strain gauges. Respiratory pauses (five seconds or longer) were determined for all sleep stages. Respiratory rate was scored only in the first and last sleep cycles and during ten waking minutes before sleep onset. Respiratory rate was significantly affected by wakefulness or stage of sleep: highest in wakefulness and stage 1, lowest in stage 2 of the last sleep cycle. Regularity of respiratory rate showed a similar effect. Variance of respiratory rate was significantly lower in girls than boys. Respiratory pauses during sleep were seen in every child, ranging from 3 to 40 pauses per night (average, 17.2 for boys and 18.0 for girls). Significantly greater numbers of pauses per minute were seen in stage 1 and rapid eye movement (REM) sleep than in stages 2, 3 and 4. The longest respiratory pause was 25 seconds. The conclusion is made that a small number of respiratory pauses during sleep are normal in children of this age.     

Psychosocial and psychological interventions for prevention of postnatal depression: systematic review

Objective To assess the effects of psychosocial and psychological interventions compared with usual antepartum, intrapartum, or postpartum care on the risk of postnatal depression.Data sources Medline, Embase, CINAHL, Cochrane central register of controlled trials, Cochrane pregnancy and childbirth group trials register, Cochrane depression, anxiety, and neurosis trials register, secondary references and review articles, and experts in the field.Study selection All published and unpublished randomised controlled trials of preventive psychosocial or psychological interventions in which the primary or secondary aim was a reduction in the risk of postnatal depression. All trials recruited pregnant women or new mothers less than six weeks postpartum. Eligible studies were abstracted, assessed for methodological quality, and pooled with relative risk for categorical data and weighted mean difference for continuous data.Results Fifteen trials with 7697 women were included. Although there was no overall statistically significant effect on the prevention of postnatal depression in the meta-analysis of all types of interventions (15 trials, n = 7697; relative risk 0.81, 95% confidence interval 0.65 to 1.02), these results suggest a potential reduction in postnatal depression. The only intervention to have a clear preventive effect was intensive postpartum support provided by a health professional (0.68, 0.55 to 0.84). Identifying women “at risk” assisted in the prevention of postnatal depression (0.67, 0.51 to 0.89). Interventions with only a postnatal component were more beneficial (0.76, 0.58 to 0.98) than interventions that incorporated an antenatal component. In addition, individually based interventions were more effective (0.76, 0.59 to 1.00) than group based interventions (1.03, 0.65 to 1.63).Conclusions Diverse psychosocial or psychological interventions do not significantly reduce the number of women who develop postnatal depression. The most promising intervention is the provision of intensive, professionally based postpartum support.     

Nutrigerontology: why we need a new scientific discipline to develop diets and guidelines to reduce the risk of aging‐related diseases

Many diets and nutritional advice are circulating, often based on short‐ or medium‐term clinical trials and primary outcomes, like changes in LDL cholesterol or weight. It remains difficult to assess which dietary interventions can be effective in the long term to reduce the risk of aging‐related disease and increase the (healthy) lifespan. At the same time, the scientific discipline that studies the aging process has identified some important nutrient‐sensing pathways that modulate the aging process, such as the mTOR and the insulin/insulin‐like growth factor signaling pathway. A thorough understanding of the aging process can help assessing the efficacy of dietary interventions aimed at reducing the risk of aging‐related diseases. To come to these insights, a synthesis of biogerontological, nutritional, and medical knowledge is needed, which can be framed in a new discipline called ‘nutrigerontology’.     

Neuroendocrine and neurotransmitter correlates in children with antisocial behavior

When antisocial behavior becomes a persistent pattern that affects diverse domains of children's functioning, psychiatrists refer to oppositional defiant disorder (ODD) or conduct disorder (CD). The term disruptive behavior disorder (DBD) covers both ODD and CD. Research shows that in the absence of effective interventions, the prognosis for DBD children is relatively unfavorable: their disorder can extend into adolescence, manifest itself in delinquency, and convert into other psychiatric symptoms, such as addiction or personality disorders. Although environmental factors have traditionally attracted most attention in explaining the origin and persistence of DBDs, it is important not to overlook the vulnerability of the child in the development of antisocial behavior. Relatively few studies have been conducted on the neurobiological factors involved in the development of DBDs in children. In this paper, we explain how problems in hypothalamic-pituitary-adrenal (HPA) axis and serotonergic system functioning could be important factors in the behavioral problems of DBD children. Low fear of punishment and physiological underactivity may predispose antisocial individuals to seek out stimulation or take risks and may explain poor (social) conditioning and socialization. Findings consistent with this hypothesis are presented. Finally, we explain how stress in general, and adverse early life experiences in particular, could have an impact on the development of the HPA and serotonergic systems. An investigation of the neurobiological factors involved in antisocial behavior disorder might ultimately guide the development of new forms of intervention.     

Catecholamines and the sleep-wake cycle I. EEG and behavioral arousal

The exact role of catecholamines (CA) on the sleep-wake cycle is still controversial. Critical analysis of lesion studies tends to suggest a neuromodulatory role for both dopamine (DA) and norepinephrine (NE) on EEG and behavioral arousal. Support for this view is provided by pharmacological studies in which catecholaminergic systems are activated or inhibited. Taken together they show that disturbances in the dynamic balance between neurochemical systems may alter the conditions for wake-triggering mechanisms to express at optimal levels. Large electrolytic or neurotoxic lesions which affect noradrenergic and dopaminergic structures are associated with marked and prolonged EEG changes and decreased behavioral arousal, respectively. In contrast, specific and circumscribed damage restricted to these systems is followed by a transient decrease in waking activity. Thus, results observed after large central lesions are most probably related to destruction of non-catecholaminergic neurons. Inhibition of brain CA synthesis causes behavioral sedation and a decrease in waking activity. Selective pharmacological stimulation of presynaptic alpha-adrenergic (∝ 2) receptors tends to decrease waking, while opposite effects result from ∝2-receptor blockade. Drugs with agonistic activity at postsynaptic alpha-adrenergic (∝1) sites increase EEG desynchronization, but specific blockade of ∝1-receptor does not result in marked decreases of waking EEG. In contrast, treatments which simultaneously block NE and DA receptors significantly affect waking. Beta-adrenergic receptor blockers show no conclusive effects on waking or sleep. Selective DA-receptor agonists induce biphasic effects, with low doses decreasing and large doses increasing cortical desynchronization and motility. Opposite effects are observed in laboratory animals after injection of specific DA-receptor blockers.     

The Effects of Classroom Interventions on Off-Task and Disruptive Classroom Behavior in Children with Symptoms of Attention-Deficit/Hyperactivity Disorder: A Meta-Analytic Review

Children with attention-deficit/hyperactivity disorder (ADHD) often exhibit problem behavior in class, which teachers often struggle to manage due to a lack of knowledge and skills to use classroom management strategies. The aim of this meta-analytic review was to determine the effectiveness of several types of classroom interventions (antecedent-based, consequence-based, self-regulation, combined) that can be applied by teachers in order to decrease off-task and disruptive classroom behavior in children with symptoms of ADHD. A second aim was to identify potential moderators (classroom setting, type of measure, students’ age, gender, intelligence, and medication use). Finally, it was qualitatively explored whether the identified classroom interventions also directly or indirectly affected behavioral and academic outcomes of classmates. Separate meta-analyses were performed on standardized mean differences (SMDs) for 24 within-subjects design (WSD) and 76 single-subject design (SSD) studies. Results showed that classroom interventions reduce off-task and disruptive classroom behavior in children with symptoms of ADHD (WSDs: M_SMD = 0.92; SSDs: M_SMD = 3.08), with largest effects for consequence-based (WSDs: M_SMD = 1.82) and self-regulation interventions (SSDs: M_SMD = 3.61). Larger effects were obtained in general education classrooms than in other classroom settings. No reliable conclusions could be formulated about moderating effects of type of measure and students’ age, gender, intelligence, and medication use, mainly because of power problems. Finally, classroom interventions appeared to also benefit classmates’ behavioral and academic outcomes.