Early administration of the glucose-dependent insulinotropic polypeptide receptor antagonist (Pro(3))GIP prevents the development of diabetes and related metabolic abnormalities associated with genetically inherited obesity in ob/ob mice

Aims/hypothesis Ablation of gastric inhibitory polypeptide ( GIP) receptor action is reported to protect against obesity and associated metabolic abnormalities. The aim of this study was to use prediabetic ob/ob mice to examine whether 60 days of chemical GIP receptor ablation with (Pro(3)) GIP is able to counter the development of genetic obesity-related diabetes.

Use of the Child Health Questionnaire in Children with Cerebral Palsy: A Systematic Review and Evaluation of the Psychometric Properties

Objective: To review the psychometric performance of the Child Health Questionnaire (CHQ) in samples ofchildren with cerebral palsy (CP).

Method: Four search terms were applied to five databases in a search forpapers published between 1993 and January 2007.

Results: A total of 13 papers were identified, providingdata on 1229 unique children aged 2–18 years old. Three studies reported on the reliability of the CHQ(internal consistency), whilst six studies provided evidence on various dimensions of validity (concurrent;discriminant and item discriminant validity).

Conclusions: This review identified a number ofpsychometric issues that need to be addressed. These include the assessment of additional types of reliability;an examination of the factor structure of the CHQ within the CP population; and the development ofnormative data using substantial representative samples, particularly in Europe. Until these issues areaddressed, researchers utilizing the CHQ in children with CP should be cautious about its interpretation.

Psychological problems in children with cerebral palsy: A cross-sectional European study

Objectives: To describe psychological symptoms in 8–12-year-old children with cerebral palsy; to investigate predictors of these symptoms and their impact on the child and family.

Design: A cross-sectional multi-centre survey.

Participants: Eight hundred and eighteen children with cerebral palsy, aged 8–12 years, identified from population-based registers of cerebral palsy in eight European regions and from multiple sources in one further region.

Main outcome measures: The Strengths and Difficulties Questionnaire (SDQ)P4-16 and the Total Difficulties Score (TDS) dichotomised into normal/borderline (TDS = 16) versus abnormal (TDS > 16).

Statistical analysis: Multilevel, multivariable logistic regression to relate the presence of psychological symptoms to child and family characteristics.

Results: About a quarter of the children had TDS > 16 indicating significant psychological symptoms, most commonly in the domain Peer Problems. Better gross motor function, poorer intellect, more pain, having a disabled or ill sibling and living in a town were independently associated with TDS > 16. The risk of TDS > 16 was odds ratio (OR) = .2 (95% CI: .1 to .3) comparing children with the most and least severe functional limitations; OR = 3.2 (95%CI: 2.1 to 4.8) comparing children with IQ < 70 and others; OR = 2.7 (95% CI: 1.5 to 4.6) comparing children in severe pain and others; OR = 2.7 (95% CI:1.6 to 4.6) comparing children with another disabled sibling or OR = 1.8 (95%CI: 1.2 to 2.8) no siblings and others; OR = 1.8 (95% CI: 1.1 to 2.8) comparing children resident in a town and others. Among parents who reported their child to have psychological problems, 95% said they had lasted over a year, 37% said they distressed their child and 42% said they burdened the family at least ‘quite a lot’.

Conclusions: A significant proportion of children with cerebral palsy have psychological symptoms or social impairment sufficiently severe to warrant referral to specialist services. Care must be taken in the assessment and management of children with cerebral palsy to ensure psychological problems are not overlooked and potentially preventable risk factors like pain are treated effectively. The validity of the SDQ for children with severe disability warrants further assessment.

Public awareness and views on unlicensed use of medicines in children.

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT center dot There is increasing concern about the use of those medicines in children which have not been fully studied and licensed for childhood use. Such use is not uncommon, due in large part to a lack of availability of fully licensed products and formulations that are suitable for children. center dot There is little published information on the views of the public on this important area of paediatric care. WHAT THIS STUDY ADDS center dot A survey of 1000 members of the public in Northern Ireland indicated that such use of medicines in children is not well known. center dot However, when informed about this practice, the majority believed that it would compromise safety and increase the likelihood of adverse effects. They also believed that parents/guardians should be told if their child was prescribed a medicine that had not been fully tested in children. center dot Participants in the survey indicated that they would be reluctant to involve their child in a clinical trial to help with the licensing process unless the child was suffering from a life-threatening illness. To explore awareness and views of the general public on unlicensed use of medicines in children and on the participation of children in clinical trials. Members of the public completed a questionnaire survey administered by face-to-face interview in public areas in N. Ireland. The main outcome measures were the views on unlicensed use of medicines in children and on clinical trials in children. One thousand participants (59.2% female) took part; 610 were parents. Most participants (86%) had no previous knowledge about unlicensed use of medicines in children. Being a parent did not influence this nor did being a parent of a child who suffered from a health problem (P > 0.05). Most participants (92%) felt that parents should be told about unlicensed use of medicines, with the doctor most frequently selected as the person who should inform parents. At the outset, only 1.8% of participants felt that the use of medicines in children was unsafe. However, having been informed about unlicensed use of medicines, this proportion increased dramatically (62.4%; P <0.001). Views on whether participants would enter a child of their own into a clinical trial varied according to the health status of the child (P <0.05) i.e. a child in good health (3.9%) vs a child with a life-threatening condition (41.9%). There is limited public knowledge of unlicensed use of medicines in children and a general reluctance to involve children in clinical trials unless the child to be involved has a life-threatening condition.

Influence of ABCB1 polymorphisms and haplotypes on tacrolimus nephrotoxicity and dosage requirements in children with liver transplant

AIMS
The aim of this study was to investigate the in?uence of genetic polymorphisms in ABCB1 on the incidence of nephrotoxicity and tacrolimus dosage-requirements in paediatric patients following liver transplantation.
METHODS
Fifty-one paediatric liver transplant recipients receiving tacrolimus were genotyped for ABCB1 C1236>T, G2677>T and C3435>T polymorphisms. Dose-adjusted tacrolimus trough concentrations and estimated glomerular ?ltration rates (EGFR) indicative of renal toxicity were determined and correlated with the corresponding genotypes.
RESULTS
The present study revealed a higher incidence of the ABCB1 variant-alleles examined among patients with renal dysfunction (30% reduction in EGFR) at 6 months post-transplantation (1236T allele: 63.3% vs 37.5% in controls,P = 0.019; 2677T allele: 63.3% vs. 35.9%, p = 0.012; 3435T allele: 60% vs. 39.1%,P = 0.057). Carriers of the G2677->T variant allele also had a signi?cant reduction (%) in EGFR at 12 months post-transplant (mean difference = 22.6%; P = 0.031). Haplotype analysis showed a signi?cant association between T-T-T haplotypes and an increased incidence of nephrotoxicity at 6 months post-transplantation (haplotype-frequency = 52.9% in nephrotoxic patients vs 29.4% in controls; P = 0.029). Furthermore, G2677->T and C3435->T polymorphisms and T-T-T haplotypes were signi?cantly correlated with higher tacrolimus dose-adjusted pre-dose concentrations at various time points examined long after drug initiation.
CONCLUSIONS
These ?ndings suggest that ABCB1 polymorphisms in the native intestine signi?cantly in?uence tacrolimus dosage-requirement in the stable phase after transplantation. In addition, ABCB1 polymorphisms in paediatric liver transplant recipients may predispose them to nephrotoxicity over the ?rst year posttransplantation. Genotyping future transplant recipients for ABCB1 polymorphisms, therefore, could have the potential to individualize better tacrolimus immunosuppressive therapy and enhance drug safety

Impaired conflict resolution and alerting in children with ADHD: evidence from the Attention Network Task (ANT)

An important theory of attention suggests that there are three separate networks that execute discrete cognitive functions. The 'alerting' network acquires and maintains an alert state, the 'orienting' network selects information from sensory input and the 'conflict' network resolves conflict that arises between potential responses. This theory holds promise for dissociating discrete patterns of cognitive impairment in disorders where attentional deficits may often be subtle, such as in attention deficit hyperactivity disorder (ADHD).

Absence of the 7-repeat variant of the DRD4 VNTR is associated with drifting sustained attention in children with ADHD but not in controls

Many genetic studies have demonstrated an association between the 7-repeat (7r) allele of a 48-base pair variable number of tandem repeats (VNTR) in exon 3 of the DRD4 gene and the phenotype of attention deficit hyperactivity disorder (ADHD). Previous studies have shown inconsistent associations between the 7r allele and neurocognitive performance in children with ADHD. We investigated the performance of 128 children with and without ADHD on the Fixed and Random versions of the Sustained Attention to Response Task (SART). We employed timeseries analyses of reaction-time data to allow a fine-grained analysis of reaction time variability, a candidate endophenotype for ADHD. Children were grouped into either the 7r-present group (possessing at least one copy of the 7r allele) or the 7r-absent group. The ADHD group made significantly more commission errors and was significantly more variable in RT in terms of fast moment-to-moment variability than the control group, but no effect of genotype was found on these measures. Children with ADHD without the 7r allele made significantly more omission errors, were significantly more variable in the slow frequency domain and showed less sensitivity to the signal (d') than those children with ADHD the 7r and control children with or without the 7r. These results highlight the utility of time-series analyses of reaction time data for delineating the neuropsychological deficits associated with ADHD and the DRD4 VNTR. Absence of the 7-repeat allele in children with ADHD is associated with a neurocognitive profile of drifting sustained attention that gives rise to variable and inconsistent performance. (c) 2008 Wiley-Liss, Inc.

Psychological problems in children with hemiplegia: a European multicentre survey

Objective: To describe the prevalence and determinants of psychological problems in European children with hemiplegia. Design: Cross-sectional survey. Setting: Home visits in nine European regions by research associates who administered standard questionnaires to parents. Patients: 279 children with hemiplegia aged 8–12 years were recruited from population-based case registers. Outcome measure: Strengths and Difficulties Questionnaire comprising emotion, conduct, hyperactivity, peer problems and prosocial domains. An “impact score” (IS) measures the social and psychological impact of the child’s difficulties. Results: Children with hemiplegia had higher mean scores on the total difficulties score (TDS) compared with a normative sample (p<0.001). 48% and 57% of children, respectively, had borderline–abnormal TDS and IS. Significant, independent associations were observed between intellectual impairment and an increased risk for hyperactivity (odds ratio; OR 8.4, 95% CI 3.4 to 20.8), peer problems (OR 3.1, 95% CI 1.7 to 5.5), psychological and social impact (OR 3.0, 95% CI 1.6 to 5.6) when children with an intellectual quotient (IQ) <50 were compared with those with an IQ >70. Boys had an increased risk for conduct (OR 2.1, 95% CI 1.2 to 3.7) and hyperactivity disorders (OR 2.5, 95% CI 1.4 to 4.6). Poor self-esteem was associated with an increased risk for peer problems (OR 5.8, 95% CI 2.5 to 13.4) and poor prosocial skills (OR 7.5, 95% CI 2.4 to 23.2) compared with those with high self-esteem. Other determinants of psychological adjustment were impaired communication, severe pain and living with a single parent. Conclusions: Many of the psychological problems identified are amenable to treatment. Special attention should be given to those at highest risk of developing psychological difficulties.

Shyness and face scanning in children

Contrary to popular beliefs, a recent empirical study using eye tracking has shown that a non-clinical sample of socially anxious adults did not avoid the eyes during face scanning. Using eye-tracking measures, we sought to extend these findings by examining the relation between stable shyness and face scanning patterns in a non-clinical sample of 11-year-old children. We found that shyness was associated with longer dwell time to the eye region than the mouth, suggesting that some shy children were not avoiding the eyes. Shyness was also correlated with fewer first fixations to the nose, which is thought to reflect the typical global strategy of face processing. Present results replicate and extend recent work on social anxiety and face scanning in adults to shyness in children. These preliminary findings also provide support for the notion that some shy children may be hypersensitive to detecting social cues and intentions in others conveyed by the eyes. Theoretical and practical implications for understanding the social cognitive correlates and treatment of shyness are discussed. (C) 2009 Elsevier Ltd. All rights reserved.