Zeitschrift Fur Kinder-und Jugendpsychiatrie Und Psychotherapie, 2008
A panel of experts from several European countries has accomplished a systematic review of publis... more A panel of experts from several European countries has accomplished a systematic review of published and unpublished data on the use of long-acting medications in ADHD and hyperkinetic disorders, on the basis of which practical recommendations for the application of these medications have been developed. The current article outlines results of this analysis, comparing the effect sizes and numbers-needed to-treat for extended-release stimulant preparations and atomoxetine (ATX). It is concluded (1) that long-acting preparations should be licensed and used. (2) However, they should not completely replace short-acting medications, in view of costs as well as the greater flexibility of dosing. Individual choices of therapy are necessary. (3) Both ATX and retarded-release stimulants should be available.
A non-parametric implementation of the bivariate Dale model (BDM) is presented as an extension of... more A non-parametric implementation of the bivariate Dale model (BDM) is presented as an extension of the generalized additive model (GAM) of Hastie and Tibshirani. The original BDM is an example of a bivariate generalized linear model. In this paper smoothing is introduced on the marginal as well as on the association level. Our non-parametric procedure can be used as a diagnostic tool for identifying parametric transformations of the covariates in the linear BDM, hence it also provides a kind of goodness-of-fit test for a bivariate generalized linear model. Cubic smoothing spline functions for the covariates are estimated by maximizing a penalized version of the log-likelihood. The method is applied to two studies. The first study is the classical Wisconsin Epidemiologic Study of Diabetic Retinopathy. The second study is a twin study, where the association between the elements of twin pairs is of primary interest. The results show that smoothing on the association level can give a significant improvement to the model fit.
Social Psychiatry and Psychiatric Epidemiology, 2001
Background: Twin studies suggest that environmental effects on the development of child psychopat... more Background: Twin studies suggest that environmental effects on the development of child psychopathology largely involve nonshared environmental processes. However, the influence of the nonshared environment may have been overestimated, as the relationship between environment and behaviour may be genetically mediated. A direct measure of the nonshared environment (using the Sibling Inventory of Differential Experience – SIDE) was investigated in relation
At the age of 16–18 years, outcome was prospectively assessed in a general population sample of f... more At the age of 16–18 years, outcome was prospectively assessed in a general population sample of four behavioural groups, defined at 6–7 year old: a pure pervasively hyperactive group (N=31), a mixed hyperactive conduct problem group (N=20), a pure conduct problem group (N=18) and a normal control group (N=29). The objective of the present paper is to describe outcome in
The validity of self-report measurement varies widely according to the type of behaviour investig... more The validity of self-report measurement varies widely according to the type of behaviour investigated. For behaviour of overactivity and inattention, adolescents seem to underestimate their problems. Well validated instruments for self-report of attention deficit and hyperactivity disorder (ADHD) are lacking yet, and research on ADHD beyond childhood relies quite heavily on self-report. In this study, an attempt is made to
Attention-deficit/hyperactivity disorder (ADHD) is typically treated over extended periods; howev... more Attention-deficit/hyperactivity disorder (ADHD) is typically treated over extended periods; however, few placebo-controlled, long-term studies of efficacy have been reported. In a global multicenter study, children and adolescents who responded to an initial 12-week, open-label period of treatment with atomoxetine, a nonstimulant treatment for ADHD, were randomized to continued atomoxetine treatment or placebo for 9 months under double-blind conditions. A total of 416 patients completed acute atomoxetine treatment and were randomized. At end point, atomoxetine was superior to placebo in preventing relapse defined as a return to 90% of baseline symptom severity (proportion relapsing: atomoxetine 65 of 292 [22.3%], placebo 47 of 124 [37.9%], p =.002). The proportion of patients with a 50% worsening in symptoms post-randomization was also lower on atomoxetine (atomoxetine 83 of 292 [28.4%], placebo 59 of 124 [47.6%], p <.001). Compared with patients in the placebo group, atomoxetine-treated patients had superior psychosocial functioning at end point. Discontinuations for adverse events were low in both groups, and tolerability was similar to that observed in acute treatment trials. In patients who responded favorably to 12 weeks of initial treatment, atomoxetine was superior to placebo in maintaining response for the ensuing 9 months. This result supports the value of maintenance treatment with atomoxetine in patients with ADHD who respond to initial treatment.
In order to investigate the possible causal relationships between hyperactivity and educational u... more In order to investigate the possible causal relationships between hyperactivity and educational underachievement that might account for their frequent co-occurrence, four groups of boys, defined by the presence or absence of hyperactivity and specific reading retardation, were identified in an epidemiological study of 7 8-year-old children. They were examined in detail by means of parental interviews and psychological tests and reassessed 9 years later at the age of 16-18 years on a similar range of measures. The findings provided little support for the idea that persistent reading disabilities either lead to the development of hyperactivity de novo or increased the likelihood that hyperactivity, when present, would persist. Similarly, although features of hyperactivity persisted to follow-up, there was little evidence that they either lead to the development of reading disabilities or increased the likelihood that reading disabilities, when present, would persist. Socioeconomic adversity and a history of speech therapy were more common in the group with both hyperactivity and reading disability, but the strength of these associations made it unlikely that these factors could account for the frequent co-occurrence of the two conditions.
A systematic review of published and unpublished data on the use of long-acting medications in AD... more A systematic review of published and unpublished data on the use of long-acting medications in ADHD and hyperkinetic disorder is reported, giving effect sizes and numbers-to-treat for extended-release stimulant preparations and atomoxetine (ATX). A panel of experts from several European countries used the review to make recommendations about the use of these drugs in practice, and conclusions are reported: (1) Long-acting preparations should be available and used; (2) They should not replace short-acting drugs (which will be the initial treatment for many children for reasons of cost and flexibility of dosing). Individual clinical choice is needed. (3) Both ATX and extended-release preparations of stimulants should be available. The choice will depend upon the circumstances, and detailed recommendations are made.
Journal of the American Academy of Child and Adolescent Psychiatry, 2014
Behavioral interventions are recommended as attention-deficit/hyperactivity disorder (ADHD) treat... more Behavioral interventions are recommended as attention-deficit/hyperactivity disorder (ADHD) treatments. However, a recent meta-analysis found no effects on core ADHD symptoms when raters were probably blind to treatment allocation. The present analysis is extended to a broader range of child and parent outcomes. A systematic search in PubMed, Ovid, Web of Knowledge, ERIC, and CINAHAL databases (up to February 5, 2013) identified published randomized controlled trials measuring a range of patient and parent outcomes for children and adolescents diagnosed with ADHD (or who met validated cutoffs on rating scales). Thirty-two of 2,057 nonduplicate screened records were analyzed. For assessments made by individuals closest to the treatment setting (usually unblinded), there were significant improvements in parenting quality (standardized mean difference [SMD] for positive parenting 0.68; SMD for negative parenting 0.57), parenting self-concept (SMD 0.37), and child ADHD (SMD 0.35), condu...
Many studies suggest that pregnancy and birth complications (PBCs) are environmental risk factors... more Many studies suggest that pregnancy and birth complications (PBCs) are environmental risk factors for child psychopathology. However, it is not known whether the effects of PBCs occur independently of genetic predisposition. The current study examined the possibility of gene-environment interaction in a twin design. The East Flanders Prospective Twin Survey prospectively records the births of all twin pairs born in East Flanders, Belgium. The current study included 760 twin pairs aged 6-17 years. Multilevel regression analysis was used to assess the effects of several PBCs collected around the time of birth. Using structural equation modelling, ACE models assuming additive genetic (A), shared environmental (C) and unique environmental (E) influences, were compared in order to examine whether the contribution of genetic factors to parent-rated child problem behaviour varied as a function of exposure to dichotomously and continuously defined PBCs. A main independent effect of lower birth weight, corrected for gestational age (small for gestational age--SGA), on child problem behaviour was found. In addition, there was an interaction between genetic influence and SGA, in that being smaller for gestational age resulted in less influence of additive genetic factors on individual differences in problem behaviour. Results are suggestive of negative gene-birth weight interaction. Children who are SGA are less sensitive to the genetic effects, and those with high genetic vulnerability are less sensitive to the effects of being SGA in bringing about post-natal mental health effects.
Journal of the American Academy of Child & Adolescent Psychiatry, 2004
Attention-deficit/hyperactivity disorder (ADHD) is typically treated over extended periods; howev... more Attention-deficit/hyperactivity disorder (ADHD) is typically treated over extended periods; however, few placebo-controlled, long-term studies of efficacy have been reported. In a global multicenter study, children and adolescents who responded to an initial 12-week, open-label period of treatment with atomoxetine, a nonstimulant treatment for ADHD, were randomized to continued atomoxetine treatment or placebo for 9 months under double-blind conditions. A total of 416 patients completed acute atomoxetine treatment and were randomized. At end point, atomoxetine was superior to placebo in preventing relapse defined as a return to 90% of baseline symptom severity (proportion relapsing: atomoxetine 65 of 292 [22.3%], placebo 47 of 124 [37.9%], p =.002). The proportion of patients with a 50% worsening in symptoms post-randomization was also lower on atomoxetine (atomoxetine 83 of 292 [28.4%], placebo 59 of 124 [47.6%], p <.001). Compared with patients in the placebo group, atomoxetine-treated patients had superior psychosocial functioning at end point. Discontinuations for adverse events were low in both groups, and tolerability was similar to that observed in acute treatment trials. In patients who responded favorably to 12 weeks of initial treatment, atomoxetine was superior to placebo in maintaining response for the ensuing 9 months. This result supports the value of maintenance treatment with atomoxetine in patients with ADHD who respond to initial treatment.
... Exceptions include low proxy–child correlations for physical functioning (Czyzewski, Mariotto... more ... Exceptions include low proxy–child correlations for physical functioning (Czyzewski, Mariotto, Bartholomew, LeCompte, & Sockrider, 1994; Theunissen et al., 1998) and high correlations for social interaction items (Langeveld, Koot, & Passchier, 1997). ...
In the last few decades, there has been a remarkable increase in the number of children and adole... more In the last few decades, there has been a remarkable increase in the number of children and adolescents presenting with psychiatric complaints to the emergency department in the USA. In Europe, however, less is known about the paediatric psychiatric emergency population. This study provides a clinical and demographic profile of this population and its service use in a European context. From 2003 to 2008, we registered 989 paediatric psychiatric patients consulting the psychiatric emergency services (PES) of a large university hospital in Belgium. During this period the number of patients increased more than three-fold. Patients were predominantly female (57.3%) and adolescent (83.3%) and mostly referred for hostility and violence towards others (18.5%) and suicidal ideation (17.8%). For about 1/4 of the patients, PES was the first ever mental health treatment contact. PES could serve as a place for early detection and intervention and as an entry point to mental health services.
Zeitschrift Fur Kinder-und Jugendpsychiatrie Und Psychotherapie, 2008
A panel of experts from several European countries has accomplished a systematic review of publis... more A panel of experts from several European countries has accomplished a systematic review of published and unpublished data on the use of long-acting medications in ADHD and hyperkinetic disorders, on the basis of which practical recommendations for the application of these medications have been developed. The current article outlines results of this analysis, comparing the effect sizes and numbers-needed to-treat for extended-release stimulant preparations and atomoxetine (ATX). It is concluded (1) that long-acting preparations should be licensed and used. (2) However, they should not completely replace short-acting medications, in view of costs as well as the greater flexibility of dosing. Individual choices of therapy are necessary. (3) Both ATX and retarded-release stimulants should be available.
A non-parametric implementation of the bivariate Dale model (BDM) is presented as an extension of... more A non-parametric implementation of the bivariate Dale model (BDM) is presented as an extension of the generalized additive model (GAM) of Hastie and Tibshirani. The original BDM is an example of a bivariate generalized linear model. In this paper smoothing is introduced on the marginal as well as on the association level. Our non-parametric procedure can be used as a diagnostic tool for identifying parametric transformations of the covariates in the linear BDM, hence it also provides a kind of goodness-of-fit test for a bivariate generalized linear model. Cubic smoothing spline functions for the covariates are estimated by maximizing a penalized version of the log-likelihood. The method is applied to two studies. The first study is the classical Wisconsin Epidemiologic Study of Diabetic Retinopathy. The second study is a twin study, where the association between the elements of twin pairs is of primary interest. The results show that smoothing on the association level can give a significant improvement to the model fit.
Social Psychiatry and Psychiatric Epidemiology, 2001
Background: Twin studies suggest that environmental effects on the development of child psychopat... more Background: Twin studies suggest that environmental effects on the development of child psychopathology largely involve nonshared environmental processes. However, the influence of the nonshared environment may have been overestimated, as the relationship between environment and behaviour may be genetically mediated. A direct measure of the nonshared environment (using the Sibling Inventory of Differential Experience – SIDE) was investigated in relation
At the age of 16–18 years, outcome was prospectively assessed in a general population sample of f... more At the age of 16–18 years, outcome was prospectively assessed in a general population sample of four behavioural groups, defined at 6–7 year old: a pure pervasively hyperactive group (N=31), a mixed hyperactive conduct problem group (N=20), a pure conduct problem group (N=18) and a normal control group (N=29). The objective of the present paper is to describe outcome in
The validity of self-report measurement varies widely according to the type of behaviour investig... more The validity of self-report measurement varies widely according to the type of behaviour investigated. For behaviour of overactivity and inattention, adolescents seem to underestimate their problems. Well validated instruments for self-report of attention deficit and hyperactivity disorder (ADHD) are lacking yet, and research on ADHD beyond childhood relies quite heavily on self-report. In this study, an attempt is made to
Attention-deficit/hyperactivity disorder (ADHD) is typically treated over extended periods; howev... more Attention-deficit/hyperactivity disorder (ADHD) is typically treated over extended periods; however, few placebo-controlled, long-term studies of efficacy have been reported. In a global multicenter study, children and adolescents who responded to an initial 12-week, open-label period of treatment with atomoxetine, a nonstimulant treatment for ADHD, were randomized to continued atomoxetine treatment or placebo for 9 months under double-blind conditions. A total of 416 patients completed acute atomoxetine treatment and were randomized. At end point, atomoxetine was superior to placebo in preventing relapse defined as a return to 90% of baseline symptom severity (proportion relapsing: atomoxetine 65 of 292 [22.3%], placebo 47 of 124 [37.9%], p =.002). The proportion of patients with a 50% worsening in symptoms post-randomization was also lower on atomoxetine (atomoxetine 83 of 292 [28.4%], placebo 59 of 124 [47.6%], p <.001). Compared with patients in the placebo group, atomoxetine-treated patients had superior psychosocial functioning at end point. Discontinuations for adverse events were low in both groups, and tolerability was similar to that observed in acute treatment trials. In patients who responded favorably to 12 weeks of initial treatment, atomoxetine was superior to placebo in maintaining response for the ensuing 9 months. This result supports the value of maintenance treatment with atomoxetine in patients with ADHD who respond to initial treatment.
In order to investigate the possible causal relationships between hyperactivity and educational u... more In order to investigate the possible causal relationships between hyperactivity and educational underachievement that might account for their frequent co-occurrence, four groups of boys, defined by the presence or absence of hyperactivity and specific reading retardation, were identified in an epidemiological study of 7 8-year-old children. They were examined in detail by means of parental interviews and psychological tests and reassessed 9 years later at the age of 16-18 years on a similar range of measures. The findings provided little support for the idea that persistent reading disabilities either lead to the development of hyperactivity de novo or increased the likelihood that hyperactivity, when present, would persist. Similarly, although features of hyperactivity persisted to follow-up, there was little evidence that they either lead to the development of reading disabilities or increased the likelihood that reading disabilities, when present, would persist. Socioeconomic adversity and a history of speech therapy were more common in the group with both hyperactivity and reading disability, but the strength of these associations made it unlikely that these factors could account for the frequent co-occurrence of the two conditions.
A systematic review of published and unpublished data on the use of long-acting medications in AD... more A systematic review of published and unpublished data on the use of long-acting medications in ADHD and hyperkinetic disorder is reported, giving effect sizes and numbers-to-treat for extended-release stimulant preparations and atomoxetine (ATX). A panel of experts from several European countries used the review to make recommendations about the use of these drugs in practice, and conclusions are reported: (1) Long-acting preparations should be available and used; (2) They should not replace short-acting drugs (which will be the initial treatment for many children for reasons of cost and flexibility of dosing). Individual clinical choice is needed. (3) Both ATX and extended-release preparations of stimulants should be available. The choice will depend upon the circumstances, and detailed recommendations are made.
Journal of the American Academy of Child and Adolescent Psychiatry, 2014
Behavioral interventions are recommended as attention-deficit/hyperactivity disorder (ADHD) treat... more Behavioral interventions are recommended as attention-deficit/hyperactivity disorder (ADHD) treatments. However, a recent meta-analysis found no effects on core ADHD symptoms when raters were probably blind to treatment allocation. The present analysis is extended to a broader range of child and parent outcomes. A systematic search in PubMed, Ovid, Web of Knowledge, ERIC, and CINAHAL databases (up to February 5, 2013) identified published randomized controlled trials measuring a range of patient and parent outcomes for children and adolescents diagnosed with ADHD (or who met validated cutoffs on rating scales). Thirty-two of 2,057 nonduplicate screened records were analyzed. For assessments made by individuals closest to the treatment setting (usually unblinded), there were significant improvements in parenting quality (standardized mean difference [SMD] for positive parenting 0.68; SMD for negative parenting 0.57), parenting self-concept (SMD 0.37), and child ADHD (SMD 0.35), condu...
Many studies suggest that pregnancy and birth complications (PBCs) are environmental risk factors... more Many studies suggest that pregnancy and birth complications (PBCs) are environmental risk factors for child psychopathology. However, it is not known whether the effects of PBCs occur independently of genetic predisposition. The current study examined the possibility of gene-environment interaction in a twin design. The East Flanders Prospective Twin Survey prospectively records the births of all twin pairs born in East Flanders, Belgium. The current study included 760 twin pairs aged 6-17 years. Multilevel regression analysis was used to assess the effects of several PBCs collected around the time of birth. Using structural equation modelling, ACE models assuming additive genetic (A), shared environmental (C) and unique environmental (E) influences, were compared in order to examine whether the contribution of genetic factors to parent-rated child problem behaviour varied as a function of exposure to dichotomously and continuously defined PBCs. A main independent effect of lower birth weight, corrected for gestational age (small for gestational age--SGA), on child problem behaviour was found. In addition, there was an interaction between genetic influence and SGA, in that being smaller for gestational age resulted in less influence of additive genetic factors on individual differences in problem behaviour. Results are suggestive of negative gene-birth weight interaction. Children who are SGA are less sensitive to the genetic effects, and those with high genetic vulnerability are less sensitive to the effects of being SGA in bringing about post-natal mental health effects.
Journal of the American Academy of Child & Adolescent Psychiatry, 2004
Attention-deficit/hyperactivity disorder (ADHD) is typically treated over extended periods; howev... more Attention-deficit/hyperactivity disorder (ADHD) is typically treated over extended periods; however, few placebo-controlled, long-term studies of efficacy have been reported. In a global multicenter study, children and adolescents who responded to an initial 12-week, open-label period of treatment with atomoxetine, a nonstimulant treatment for ADHD, were randomized to continued atomoxetine treatment or placebo for 9 months under double-blind conditions. A total of 416 patients completed acute atomoxetine treatment and were randomized. At end point, atomoxetine was superior to placebo in preventing relapse defined as a return to 90% of baseline symptom severity (proportion relapsing: atomoxetine 65 of 292 [22.3%], placebo 47 of 124 [37.9%], p =.002). The proportion of patients with a 50% worsening in symptoms post-randomization was also lower on atomoxetine (atomoxetine 83 of 292 [28.4%], placebo 59 of 124 [47.6%], p <.001). Compared with patients in the placebo group, atomoxetine-treated patients had superior psychosocial functioning at end point. Discontinuations for adverse events were low in both groups, and tolerability was similar to that observed in acute treatment trials. In patients who responded favorably to 12 weeks of initial treatment, atomoxetine was superior to placebo in maintaining response for the ensuing 9 months. This result supports the value of maintenance treatment with atomoxetine in patients with ADHD who respond to initial treatment.
... Exceptions include low proxy–child correlations for physical functioning (Czyzewski, Mariotto... more ... Exceptions include low proxy–child correlations for physical functioning (Czyzewski, Mariotto, Bartholomew, LeCompte, & Sockrider, 1994; Theunissen et al., 1998) and high correlations for social interaction items (Langeveld, Koot, & Passchier, 1997). ...
In the last few decades, there has been a remarkable increase in the number of children and adole... more In the last few decades, there has been a remarkable increase in the number of children and adolescents presenting with psychiatric complaints to the emergency department in the USA. In Europe, however, less is known about the paediatric psychiatric emergency population. This study provides a clinical and demographic profile of this population and its service use in a European context. From 2003 to 2008, we registered 989 paediatric psychiatric patients consulting the psychiatric emergency services (PES) of a large university hospital in Belgium. During this period the number of patients increased more than three-fold. Patients were predominantly female (57.3%) and adolescent (83.3%) and mostly referred for hostility and violence towards others (18.5%) and suicidal ideation (17.8%). For about 1/4 of the patients, PES was the first ever mental health treatment contact. PES could serve as a place for early detection and intervention and as an entry point to mental health services.
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