Paediatrics (RCH) - Research Publications
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ItemAmfetamine and methylphenidate medications for attention-deficit/hyperactivity disorder: complementary treatment options(SPRINGER, 2012-09)Attention-deficit/hyperactivity disorder (ADHD) is one of the most common neurodevelopmental disorders among school-aged children. It is highly symptomatic and associated with significant impairment. This review examines the role of stimulant medications in the treatment of children and adolescents with ADHD. Published clinical studies that compared methylphenidate- and amfetamine-based stimulants in children and adolescents with ADHD support the therapeutic utility of stimulant treatments, and suggest robust efficacy and acceptable safety outcomes in groups treated with either stimulant. Evidence-based guidelines agree that each patient with ADHD is unique and individual treatment strategies that incorporate both drug and non-drug treatment options should be sought. In seeking to optimize individual response and outcomes to stimulant therapy, important considerations include the selection of stimulant class, the choice of long- or short-acting stimulant formulations, addressing effectively any emergent adverse effects and strategies aimed at enhancing adherence to dosing regimen and persistence on therapy.
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ItemEfficacy of two once-daily methylphenidate formulations compared across dose levels at different times of the day: Preliminary indications from a secondary analysis of the COMACS study data(BMC, 2004)BACKGROUND: Methylphenidate (MPH) is commonly prescribed in the treatment of Attention-Deficit/Hyperactivity Disorder or ADHD. Concerta and Metadate CD are once-daily formulations of MPH using different delivery mechanisms resulting in different pharmacokinetic profiles. A recent study (COMACS) showed that for near-milligram (mg) equivalent daily doses, Metadate CD provides greater symptom control in the morning (1.5 through 4.5 hours post-dose), while Concerta provides greater control in the early evening (12 hours post-dose). Non-inferential comparison of effects for different dose levels of the two formulations suggested that equivalent levels of morning symptom control could be obtained with lower daily doses of Metadate CD than Concerta; the situation being reversed in the evening. The current paper presents a secondary analysis that provides a statistical test of these observations. METHOD: The COMACS study was a multi-center, double-blind crossover study of Metadate CD, Concerta and placebo with each treatment administered for 1 week. Children were assigned on the basis of their pre-trial dosage to either high (Metadate CD 60 mg; Concerta 54 mg), medium (Metadate CD 40 mg; Concerta 36 mg) or low doses (Metadate CD 20 mg; Concerta 18 mg) of MPH, and attended a laboratory school on the 7th day for assessment at 7 sessions across the day. For the post-hoc comparisons across dose levels presented here, total SKAMP scores with the active treatments (adjusted for placebo response) were analyzed using an analysis of covariance, with a combined measure modeling placebo response across all time period as the covariate. RESULTS: Symptom control from 1.5 through 6.0 hours post-dose was as good with lower doses of Metadate CD (20 and 40 mg) as with higher doses of Concerta (36 and 54 mg, respectively). Lower daily doses of Concerta (18 and 36 mg) and higher doses of Metadate CD (40 and 60 mg, respectively) gave equivalent control at 7.5 and 12 hours with Metadate CD giving better control from1.5 through 6.0 hours post-dose. CONCLUSIONS: Different delivery profiles of Metadate CD and Concerta can be exploited to limit total daily exposure to MPH while at the same targeting a specific, especially clinically significant, period of the day. These results need to be confirmed in a study in which children are randomly allocated to different dose levels of the two formulations and plasma MPH concentrations are assessed simultaneously.
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ItemAvoiding the 'twilight zone': Recommendations for the transition of services from adolescence to adulthood for young people with ADHD(BMC, 2011-11-03)Attention deficit hyperactivity disorder (ADHD) is a common childhood disorder that frequently persists into adulthood. However, in the UK, there is a paucity of adult services available for the increasing number of young people with ADHD who are now graduating from child services. Furthermore, there is limited research investigating the transition of young people with ADHD from child to adult services and a lack of guidance on how to achieve this effectively. This paper reviews the difficulties of young people with ADHD and their families who are transitioning between services; we review transition from the child and adult health teams' perspectives and identify barriers to the transition process. We conclude with recommendations on how to develop transition services for young people with ADHD.
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ItemMolecular genetics of attention-deficit/hyperactivity disorder: an overview(SPRINGER, 2010-03)As heritability is high in attention-deficit/hyperactivity disorder (ADHD), genetic factors must play a significant role in the development and course of this disorder. In recent years a large number of studies on different candidate genes for ADHD have been published, most have focused on genes involved in the dopaminergic neurotransmission system, such as DRD4, DRD5, DAT1/SLC6A3, DBH, DDC. Genes associated with the noradrenergic (such as NET1/SLC6A2, ADRA2A, ADRA2C) and serotonergic systems (such as 5-HTT/SLC6A4, HTR1B, HTR2A, TPH2) have also received considerable interest. Additional candidate genes related to neurotransmission and neuronal plasticity that have been studied less intensively include SNAP25, CHRNA4, NMDA, BDNF, NGF, NTF3, NTF4/5, GDNF. This review article provides an overview of these candidate gene studies, and summarizes findings from recently published genome-wide association studies (GWAS). GWAS is a relatively new tool that enables the identification of new ADHD genes in a hypothesis-free manner. Although these latter studies could be improved and need to be replicated they are starting to implicate processes like neuronal migration and cell adhesion and cell division as potentially important in the aetiology of ADHD and have suggested several new directions for future ADHD genetics studies.
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ItemThe quality of life of children with attention deficit/hyperactivity disorder: a systematic review(SPRINGER, 2010-02)Quality of life (QoL) describes an individual's subjective perception of their position in life as evidenced by their physical, psychological, and social functioning. QoL has become an increasingly important measure of outcome in child mental health clinical work and research. Here we provide a systematic review of QoL studies in children and young people with attention deficit hyperactivity disorder (ADHD) and address three main questions. (1) What is the impact of ADHD on QoL? (2) What are the relationships between ADHD symptoms, functional impairment and the mediators and moderators of QoL in ADHD? (3) Does the treatment of ADHD impact on QoL? Databases were systematically searched to identify research studies describing QoL in ADHD. Thirty six relevant articles were identified. Robust negative effects on QoL are reported by the parents of children with ADHD across a broad range of psycho-social, achievement and self evaluation domains. Children with ADHD rate their own QoL less negatively than their parents and do not always seeing themselves as functioning less well than healthy controls. ADHD has a comparable overall impact on QoL compared to other mental health conditions and severe physical disorders. Increased symptom level and impairment predicts poorer QoL. The presence of comorbid conditions or psychosocial stressors helps explain these effects. There is emerging evidence that QoL improves with effective treatment. In conclusion, ADHD seriously compromises QoL especially when seen from a parents' perspective. QoL outcomes should be included as a matter of course in future treatment studies.
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ItemEuropean guidelines on managing adverse effects of medication for ADHD(SPRINGER, 2011-01)The safety of ADHD medications is not fully known. Concerns have arisen about both a lack of contemporary-standard information about medications first licensed several decades ago, and signals of possible harm arising from more recently developed medications. These relate to both relatively minor adverse effects and extremely serious issues such as sudden cardiac death and suicidality. A guidelines group of the European Network for Hyperkinetic Disorders (EUNETHYDIS) has therefore reviewed the literature, recruited renowned clinical subspecialists and consulted as a group to examine these concerns. Some of the effects examined appeared to be minimal in impact or difficult to distinguish from risk to untreated populations. However, several areas require further study to allow a more precise understanding of these risks.
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ItemEunethydis: a statement of the ethical principles governing the relationship between the European group for ADHD guidelines, and its members, with commercial for-profit organisations(SPRINGER, 2010-09)The Eunethydis ADHD Guidelines group set out here the ethical principles governing the relationship between the group and industry. The principles set out here are provided to ensure that this is both done and seen to be done. The impetus for these guidelines comes from within the Group and is linked to the recognition for the need for an open and transparent basis for Group-industry relations, especially in the light of the present concern that the pharmaceutical industry may be exerting a growing influence on the actions of researchers and clinicians in the ADHD field.
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ItemImpact of attention-deficit/hyperactivity disorder on the patient and family: results from a European survey.(Springer Science and Business Media LLC, 2008-10-28)BACKGROUND: Children with attention-deficit/hyperactivity disorder (ADHD) often experience problems with education, interaction with others and emotional disturbances. Families of ADHD children also suffer a significant burden, in terms of strain on relationships and reduced work productivity. This parent survey assessed daily life for children with ADHD and their families. METHOD: This pan-European survey involved the completion of an on-line questionnaire by parents of children (6-18 years) with ADHD (ADHD sample) and without ADHD (normative population sample). Parents were questioned about the impact of their child's ADHD on everyday activities, general behaviour and family relationships. RESULTS: The ADHD sample comprised 910 parents and the normative population sample 995 parents. 62% of ADHD children were not currently receiving medication; 15% were receiving 6-8 hour stimulant medication and 23% 12-hour stimulant medication. Compared with the normative population sample, parents reported that ADHD children consistently displayed more demanding, noisy, disruptive, disorganised and impulsive behaviour. Significantly more parents reported that ADHD children experienced challenges throughout the day, from morning until bedtime, compared with the normative population sample. Parents reported that children with ADHD receiving 12-hour stimulant medication experienced fewer challenges during early afternoon and late afternoon/early evening than children receiving 6-8 hour stimulant medication; by late evening and bedtime however, this difference was not apparent. ADHD was reported to impact most significantly on activities such as homework, family routines and playing with other children. All relationships between ADHD children and others were also negatively affected, especially those between parent and child (72% of respondents). Parents reported that more children with ADHD experienced a personal injury in the preceding 12 months, including those requiring the attention of healthcare professionals. Although 68% of parents were satisfied with their child's current treatment, 35-40% stated that their child's ADHD symptoms needed to be more effectively treated during the afternoon and evening. CONCLUSION: This parent survey highlights the breadth of problems experienced by ADHD children and the impact throughout the day on both activities and relationships. Therefore, there is a need for treatment approaches that take into account the 24-hour impact of the disorder and include all-day coverage with effective medication.
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ItemThe validity, reliability and normative scores of the parent, teacher and self report versions of the Strengths and Difficulties Questionnaire in China.(Springer Science and Business Media LLC, 2008-04-29)BACKGROUND: The Strengths and Difficulties Questionnaire (SDQ) has become one of the most widely used measurement tools in child and adolescent mental health work across the globe. The SDQ was originally developed and validated within the UK and whilst its reliability and validity have been replicated in several countries important cross cultural issues have been raised. We describe normative data, reliability and validity of the Chinese translation of the SDQ (parent, teacher and self report versions) in a large group of children from Shanghai. METHODS: The SDQ was administered to the parents and teachers of students from 12 of Shanghai's 19 districts, aged between 3 and 17 years old, and to those young people aged between 11 and 17 years. Retest data was collected from parents and teachers for 45 students six weeks later. Data was analysed to describe normative scores, bandings and cut-offs for normal, borderline and abnormal scores. Reliability was assessed from analyses of internal consistency, inter-rater agreement, and temporal stability. Structural validity, convergent and discriminant validity were assessed. RESULTS: Full parent and teacher data was available for 1965 subjects and self report data for 690 subjects. Normative data for this Chinese urban population with bandings and cut-offs for borderline and abnormal scores are described. Principle components analysis indicates partial agreement with the original five factored subscale structure however this appears to hold more strongly for the Prosocial Behaviour, Hyperactivity - Inattention and Emotional Symptoms subscales than for Conduct Problems and Peer Problems. Internal consistency as measured by Cronbach's alpha coefficient were generally low ranging between 0.30 and 0.83 with only parent and teacher Hyperactivity - Inattention and teacher Prosocial Behaviour subscales having alpha > 0.7. Inter-rater correlations were similar to those reported previously (range 0.23 - 0.49) whilst test retest reliability was generally lower than would be expected (range 0.40 - 0.79). Convergent and discriminant validity are supported. CONCLUSION: We report mixed findings with respect the psychometric properties of the Chinese translation of the SDQ. Reliability is a particular concern particularly for Peer Problems and self ratings by adolescents. There is good support for convergent validity but only partial support for structural validity. It may be possible to resolve some of these issues by carefully examining the wording and meaning of some of the current questions.