A comparison of the clinical effectiveness and cost of specialised individually delivered parent training for preschool attention-deficit/hyperactivity disorder and a generic, group-based programme: a multi-centre, randomised controlled trial of the New Forest Parenting Programme versus Incredible Years.

The objective of this study is to compare the efficacy and cost of specialised individually delivered parent training (PT) for preschool children with attention-deficit/hyperactivity disorder (ADHD) against generic group-based PT and treatment as usual (TAU). This is a multi-centre three-arm, parallel group randomised controlled trial conducted in National Health Service Trusts. The participants included in this study were preschool children (33-54 months) fulfilling ADHD research diagnostic criteria. New Forest Parenting Programme (NFPP)-12-week individual, home-delivered ADHD PT programme; Incredible Years (IY)-12-week group-based, PT programme initially designed for children with behaviour problems were the interventions. Primary outcome-Parent ratings of child's ADHD symptoms (Swanson, Nolan & Pelham Questionnaire-SNAP-IV). Secondary outcomes-teacher ratings (SNAP-IV) and direct observations of ADHD symptoms and parent/teacher ratings of conduct problems. NFPP, IY and TAU outcomes were measured at baseline (T1) and post treatment (T2). NFPP and IY outcomes only were measured 6 months post treatment (T3). Researchers, but not therapists or parents, were blind to treatment allocation. Analysis employed mixed effect regression models (multiple imputations). Intervention and other costs were estimated using standardized approaches. NFPP and IY did not differ on parent-rated SNAP-IV, ADHD combined symptoms [mean difference - 0.009 95% CI (- 0.191, 0.173), p = 0.921] or any other measure. Small, non-significant, benefits of NFPP over TAU were seen for parent-rated SNAP-IV, ADHD combined symptoms [- 0.189 95% CI (- 0.380, 0.003), p = 0.053]. NFPP significantly reduced parent-rated conduct problems compared to TAU across scales (p values < 0.05). No significant benefits of IY over TAU were seen for parent-rated SNAP, ADHD symptoms [- 0.16 95% CI (- 0.37, 0.04), p = 0.121] or parent-rated conduct problems (p > 0.05). The cost per family of providing NFPP in the trial was significantly lower than IY (£1591 versus £2103). Although, there were no differences between NFPP and IY with regards clinical effectiveness, individually delivered NFPP cost less. However, this difference may be reduced when implemented in routine clinical practice. Clinical decisions should take into account parental preferences between delivery approaches.

Gene conversion in transgenic maize plants expressing FLP/FRT and Cre/loxP site-specific recombination systems.

DNA recombination reactions (site-specific and homologous) were monitored in the progeny of transgenic maize plants by bringing together two recombination substrates (docking sites and shuttle vectors) in the zygotes. In one combination of transgenic events, the recombination marker gene (yellow fluorescent protein gene, YFP) was activated in 1%-2% of the zygotes receiving both substrates. In other crosses, chimeric embryos and plants were identified, indicative of late recombination events taking place after the first mitotic division of the zygotes. The docking site structure remained unchanged; therefore, all recovered recombination events were classified as gene conversions. The recombinant YFP-r gene segregated as a single locus in subsequent generations. The recombination products showed evidence of homologous recombination at the 5' end of the YFP marker gene and recombinational rearrangements at the other end, consistent with the conclusion that DNA replication was involved in generation of the recombination products. Here, we demonstrate that maize zygotes are efficient at generating homologous recombination products and that the homologous recombination pathways may successfully compete with other possible DNA repair/recombination mechanisms such as site-specific recombination. These results indicate that maize zygotes provide a permissive environment for homologous recombination, offering a new strategy for gene targeting in maize.

Voice-DISC identified DSM-IV disorders among 15-year-olds in the west of Scotland.

OBJECTIVE: To report prevalence estimates of psychiatric disorder among Scottish adolescents using a self-administered computerized (Voice) version of the DISC. METHOD: A total of 1,860 15-year-olds (67%), participating in a school-based survey of health and lifestyles, completed selected modules of the Voice-DISC, producing DSM-IV diagnoses of (specific) anxiety disorders, eating disorders, depressive/dysthymic disorder, behavior disorders, and substance abuse/dependence. RESULTS: Overall prevalence of any psychiatric diagnosis, including substance abuse/dependence, was 31%, reducing to 15% with strict impairment criteria. Anxiety disorders were more common in females, behavior disorders (except attention-deficit/hyperactivity disorder) in males. Comorbidity within major diagnostic categories was considerable; that between categories was lower, although high comorbidity between conduct disorder and substance abuse/dependence was found. CONCLUSIONS: Prevalence estimates are similar to those reported in other studies, although methodological problems limit comparisons. Of particular interest are the similar or higher rates of behavior disorders, especially conduct disorders, to those in studies involving multiple informants.

Researchers BEWARE! attrition and nonparticipation at large.

There are many obstacles in undertaking psychological burns research with children and adolescents, and the more useful longitudinal studies are particularly fraught with difficulty. This work introduces and discusses the problems of attrition and nonparticipation encountered in our attempt to use a rigorous design and methodology to study this population. The aim is to provide the impetus for a more thorough, detailed review of this problem.

Study protocol for a randomized controlled trial comparing the efficacy of a specialist and a generic parenting programme for the treatment of preschool ADHD.

BACKGROUND: The New Forest Parenting Programme (NFPP) is a home-delivered, evidence-based parenting programme to target symptoms of attention-deficit/hyperactivity disorder (ADHD) in preschool children. It has been adapted for use with 'hard-to-reach' or 'difficult-to-treat' children. This trial will compare the adapted-NFPP with a generic parenting group-based programme, Incredible Years (IY), which has been recommended for children with preschool-type ADHD symptoms. METHODS/DESIGN: This multicentre randomized controlled trial comprises three arms: adapted-NFPP, IY and treatment as usual (TAU). A sample of 329 parents of preschool-aged children with a research diagnosis of ADHD enriched for hard-to-reach and potentially treatment-resistant children will be allocated to the arms in the ratio 3:3:1. Participants in the adapted-NFPP and IY arms receive an induction visit followed by 12 weekly parenting sessions of 1½ hours (adapted-NFPP) or 2½ hours (IY) over 2.5 years. Adapted-NFPP will be delivered as a one-to-one home-based intervention; IY, as a group-based intervention. TAU participants are offered a parenting programme at the end of the study. The primary objective is to test whether the adapted-NFPP produces beneficial effects in terms of core ADHD symptoms. Secondary objectives include examination of the treatment impact on secondary outcomes, a study of cost-effectiveness and examination of the mediating role of treatment-induced changes in parenting behaviour and neuropsychological function. The primary outcome is change in ADHD symptoms, as measured by the parent-completed version of the SNAP-IV questionnaire, adjusted for pretreatment SNAP-IV score. Secondary outcome measures are: a validated index of behaviour during child's solo play; teacher-reported SNAP-IV (ADHD scale); teacher and parent SNAP-IV (ODD) Scale; Eyberg Child Behaviour Inventory - Oppositional Defiant Disorder scale; Revised Client Service Receipt Inventory - Health Economics Costs measure and EuroQol (EQ5D) health-related quality-of-life measure. Follow-up measures will be collected 6 months after treatment for participants allocated to adapted-NFPP and IY. DISCUSSION: This trial will provide evidence as to whether the adapted-NFPP is more effective and cost-effective than the recommended treatment and TAU. It will also provide information about mediating factors (improved parenting and neuropsychological function) and moderating factors (parent and child genetic factors) in any increased benefit. TRIAL REGISTRATION: Current Controlled Trials, ISRCTN39288126.

A Cre/loxP-mediated self-activating gene excision system to produce marker gene free transgenic soybean plants.

Marker-gene-free transgenic soybean plants were produced by isolating a developmentally regulated embryo-specific gene promoter, app1, from Arabidopsis and developing a self-activating gene excision system using the P1 bacteriophage Cre/loxP recombination system. To accomplish this, the Cre recombinase gene was placed under control of the app1 promoter and, together with a selectable marker gene (hygromycin phosphotransferase), were cloned between two loxP recombination sites. This entire sequence was then placed between a constitutive promoter and a coding region for either beta-glucuronidase (Gus) or glyphosate acetyltransferase (Gat). Gene excision would remove the entire sequence between the two loxP sites and bring the coding region to the constitutive promoter for expression. Using this system marker gene excision occurred in over 30% of the stable transgenic events as indicated by the activation of the gus reporter gene or the gat gene in separate experiments. Transgenic plants with 1 or 2 copies of a functional excision-activated gat transgene and without any marker gene were obtained in T0 or T1 generation. This demonstrates the feasibility of using developmentally controlled promoters to mediate marker excision in soybean.

Comorbid oppositional defiant disorder and the risk of relapse during 9 months of atomoxetine treatment for attention-deficit/hyperactivity disorder.

OBJECTIVE: To examine the influence of comorbid oppositional defiant disorder (ODD) on the relative risk (RR) of relapse during 9 months of treatment with atomoxetine for attention-deficit/hyperactivity disorder (ADHD). METHOD: Four hundred and sixteen children and adolescents with ADHD whose symptoms remitted during initial 10-week, open-label atomoxetine treatment were randomly assigned to continue with atomoxetine or placebo. RESULTS: In all, 43% met criteria for comorbid ODD. A total of 17% of patients with comorbid ODD relapsed (CGI-Severity score >or= 3 and ADHD Rating Scale total score of 90% or more of baseline at study entry on two consecutive visits) during atomoxetine treatment, compared with 26% of patients without comorbid ODD (RR 0.67, 95% CI 0.42-1.06). Mean time to relapse was not significantly different [mean (SE) days to relapse, ADHD/ +ODD: 215 (7.38); ADHD/-ODD: 211 (7.61); log rank p = 0.08]. This finding is placed within the context of atomoxetine affording an overall protection against relapse compared with placebo (RR 0.59, 95% CI 0.43-0.80). CONCLUSIONS: Comorbid ODD does not influence the rate of relapse of patients with ADHD during longer-term treatment with atomoxetine. Atomoxetine protects against the relapse of ADHD symptoms regardless of the presence or absence of comorbid ODD.

A comparison of North American versus non-North American ADHD study populations.

Few large, prospective clinical studies in Europe have assessed the validity and applicability of research methods used to study ADHD in North America. To assess comparability of study populations, we examined baseline patient characteristics from a group of North American studies against those of a large European/African/Australian study. All studies used identical diagnostic assessments and inclusion criteria, with ADHD diagnosis and the presence of comorbid psychiatric conditions confirmed using the KSADS-PL. Raters were trained and assessed to ensure uniform diagnostic and symptom severity rating standards. Six hundred and four patients (mean age = 10.2 years) enrolled in the non-North American study, and 665 patients (mean age = 10.4 years) enrolled in the North American study. The proportion of girls was higher in the North American studies (29.2% vs. 10.4%, p < 0.001). In both groups, most patients had a positive family history of ADHD and previous stimulant treatment. Fewer had the inattentive subtype of ADHD, and mean severity was slightly higher in the non-North American study. Results demonstrate that, when a uniform set of rigorous, standardized diagnostic criteria are used by skilled clinicians, the patient populations identified are generally similar. This supports the practice of generalizing results from treatment studies across geographies.

Follow-up of young road accident victims.

The aim of this study was to follow-up a group of children and young people previously examined for psychological sequelae following road traffic accidents. The group was assessed 18-month postaccident to assess the severity of continuing symptoms and examine any emergence of delayed onset of posttraumatic stress reactions. Participants (N = 31) completed the Revised Impact of Event Scale and the Child Posttraumatic Stress Reaction Index. Parents completed the Child Behavior Check-List and participated in a semistructured interview. Symptoms of PTSD were noted in a quarter of participants as was delayed onset of symptoms. The role of avoidance in symptom reporting and continuing disorder is discussed.