Recombinant human growth hormone for the treatment of growth disorders in children: a systematic review and economic evaluation

Recombinant human growth hormone (rhGH) is licensed for short stature associated with growth hormone deficiency (GHD), Turner syndrome (TS), Prader-Willi syndrome (PWS), chronic renal insufficiency (CRI), short stature homeobox-containing gene deficiency (SHOX-D) and being born small for gestational age (SGA). To assess the clinical effectiveness and cost-effectiveness of rhGH compared with treatment strategies without rhGH for children with GHD, TS, PWS, CRI, SHOX-D and those born SGA. The systematic review used a priori methods. Key databases were searched (e.g. MEDLINE, EMBASE, NHS Economic Evaluation Database and eight others) for relevant studies from their inception to June 2009. A decision-analytical model was developed to determine cost-effectiveness in the UK. Two reviewers assessed titles and abstracts of studies identified by the search strategy, obtained the full text of relevant papers, and screened them against inclusion criteria. Data from included studies were extracted by one reviewer and checked by a second. Quality of included studies was assessed using standard criteria, applied by one reviewer and checked by a second. Clinical effectiveness studies were synthesised through a narrative review. Twenty-eight randomised controlled trials (RCTs) in 34 publications were included in the systematic review. GHD: Children in the rhGH group grew 2.7 cm/year faster than untreated children and had a statistically significantly higher height standard deviation score (HtSDS) after 1 year: -2.3 ± 0.45 versus -2.8 ± 0.45. TS: In one study, treated girls grew 9.3 cm more than untreated girls. In a study of younger children, the difference was 7.6 cm after 2 years. HtSDS values were statistically significantly higher in treated girls. PWS: Infants receiving rhGH for 1 year grew significantly taller (6.2 cm more) than those untreated. Two studies reported a statistically significant difference in HtSDS in favour of rhGH. CRI: rhGH-treated children in a 1-year study grew an average of 3.6 cm more than untreated children. HtSDS was statistically significantly higher in treated children in two studies. SGA: Criteria were amended to include children of 3+ years with no catch-up growth, with no reference to mid-parental height. Only one of the RCTs used the licensed dose; the others used higher doses. Adult height (AH) was approximately 4 cm higher in rhGH-treated patients in the one study to report this outcome, and AH-gain SDS was also statistically significantly higher in this group. Mean HtSDS was higher in treated than untreated patients in four other studies (significant in two). SHOX-D: After 2 years' treatment, children were approximately 6 cm taller than the control group and HtSDS was statistically significantly higher in treated children. The incremental cost per quality adjusted life-year (QALY) estimates of rhGH compared with no treatment were: 23,196 pounds for GHD, 39,460 pounds for TS, 135,311 pounds for PWS, 39,273 pounds for CRI, 33,079 pounds for SGA and 40,531 pounds for SHOX-D. The probability of treatment of each of the conditions being cost-effective at 30,000 pounds was: 95% for GHD, 19% for TS, 1% for PWS, 16% for CRI, 38% for SGA and 15% for SHOX-D.

The utility of the trans-theoretical model of behavior change in the treatment of sex offenders

This paper discusses the use of the Trans-theoretical Model of Behavior Change in the treatment of sex offenders. Constructs within this theory are the Stages of Change, Processes of Change and Decisional Balance. The first section of this paper provides a brief description of these constructs. The second section provides a brief review of research related to these constructs and discusses the implications of this research in relation to the treatment of sex offenders. The third section of this paper provides a practical description of the use of the constructs of the Trans-theoretical Model of Behaviour Change in the treatment of sex offenders. Although the validity of this model among sex offenders requires further investigation, the Trans-theoretical Model of Behavior Change appears to have considerable utility as an overarching theoretical model to conceptualize and facilitate behavior change among sex offenders.

Evaluation of an early intervention program for childhood conduct problems

Treatment outcomes of an early intervention program for childhood conduct problems were evaluated. Results provided support for the longitudinal effectiveness of the program in reducing conduct problems, social difficulties, and psychosocial impairment for young primary school aged children. Children's experience and expression of anger also reduced across the program's duration. The portfolio presents four case studies whose results provide further support for Exposure and Response Prevention (ERP) as an effective and clinically useful treatment for paediatric OCD in everyday clinical contexts.

PTSD symptomatology in children and adolescents : treatment development and evaluation

This thesis developed, implemented and evaluated a cognitive-behavioural group treatment programme for children and adolescents experiencing symptoms of PTSD (Post-traumatic stress disorder). Results of the study indicate that symptoms of sleep disturbance and flashbacks, reduced markedly in the participants, providing a useful tool in reducing synptoms experiences by individuals exposed to trauma. The Professional portfolio presents four case studies that demonstrate the clinical application of the affect of chronic illness on the psychological adjustment of the sufferer and their families.

Manualised treatment and dropout : a study of parent training

Parents who dropped out of manualised parent training programs for children with externalising behaviour disorders were interviewed retrospectively and compared prospectively with parents who continued in these programs. Parents who dropped out tended to feel more overwhelmed by their situation, because their child's behaviour problems were more severe, they had single parent status or had more than one child with difficulties.

Utility of parent training for child behaviour difficulties

Focuses on parent training for child behaviour difficulties and includes four case studies providing a detailed assessment, formulation and evaluation of the treatment. The reports illustrate the utility of parent training alone and in combination with other psychological therapies and pharmacotherapy in the treatment of different childhood disorders.

Effects of physical activity on depression and anxiety in children

This thesis study examined the direct and indirect effects of physical activity, self-efficacy and peer relations in depression and anxiety in children. No direct relationships between physical activity and symptoms of depression or anxiety were found for either sex. The portfolio, using four clinical health psychology case studies, provides an illustration of the clinical application of the transtheoretical model to four different health issues.

Relationship between verbal working memory and the SCAN-C in children with specific language impairment

Purpose: An ongoing concern with the evaluation of auditory processing disorders is the extent that assessment instruments are influenced by higher order cognitive functions. This study examined the relationship between verbal working memory and performance on the Test for Auditory Processing Disorders in Children--Revised (SCAN-C; Keith, 2000b) in children with specific language impairment (SLI) and typically developing (TD) children.

Method: Sixteen children with SLI and 16 TD children ages 8/4 to 11 years participated in the study. The children were presented with the SCAN-C and tests measuring verbal working memory.

Results: Initial comparisons revealed that the SLI group obtained significantly lower scores than the TD group on the SCAN-C. However, after controlling for verbal working memory, significant differences between the 2 groups were no longer observed. Correlational analyses revealed that the composite score from the SCAN-C was related to all tests assessing verbal working memory.

Conclusions: Performance on the SCAN-C may be related to working memory functioning. As a consequence, it is unclear whether difficulty on this task should be viewed as a problem with auditory processing or a problem with verbal working memory.

Family dynamics and the risks for child maltreatment of stepchildren

The thesis examined systemic factors that placed children in stepfamilies at greater risk of physical abuse and neglect by comparing differences between biological- and step-families on a number of known risk factors. A model describing the pathway of child abuse and neglect for children living in stepfamilies was developed to aid in prevention.The portfolio presents four case studies which demonstrate the impact of disruptions to attachment experiences and the sequelae on psychological functioning and how the associated affect dysregulation may be linked to attachment disruptions.

Increased erythrocyte eicosapentaenoic acid and docosahexaenoic acid are associated with improved attention and behavior in children with ADHD in a randomized controlled three-way crossover trial

OBJECTIVE: To investigate effects of omega-3 polyunsaturated fatty acids (n-3 PUFA) docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) on attention, literacy, and behavior in children with ADHD.

METHOD: Ninety children were randomized to consume supplements high in EPA, DHA, or linoleic acid (control) for 4 months each in a crossover design. Erythrocyte fatty acids, attention, cognition, literacy, and Conners' Parent Rating Scales (CPRS) were measured at 0, 4, 8, 12 months.

RESULTS: Fifty-three children completed the treatment. Outcome measures showed no significant differences between the three treatments. However, in children with blood samples (n = 76-46), increased erythrocyte EPA + DHA was associated with improved spelling (r = .365, p < .001) and attention (r = -.540, p < .001) and reduced oppositional behavior (r = -.301, p < .003), hyperactivity (r = -.310, p < .001), cognitive problems (r = -.326, p < .001), Diagnostic and Statistical Manual of Mental Disorders (4th ed.; DSM-IV) hyperactivity (r = -.270, p = .002) and DSM-IV inattention (r = -.343, p < .001).

CONCLUSION: Increasing erythrocyte DHA and EPA via dietary supplementation may improve behavior, attention, and literacy in children with ADHD.

Parent management training, comorbidity, and treatment of children with oppositional defiant disorder

This study found that Parent Management Training was a successful treatment for promary school aged children who were referred to a mental health clinic and diagnosed with Oppositional Defiant Disorder. The positive outcome was not affected by the child having comorbid disorders. These findings have relevance to the clinical field.

A randomised, double blind, placebo-controlled trial of a fixed dose of N-acetyl cysteine in children with autistic disorder

OBJECTIVE: Oxidative stress, inflammation and heavy metals have been implicated in the aetiology of autistic disorder. N-acetyl cysteine has been shown to modulate these pathways, providing a rationale to trial N-acetyl cysteine for autistic disorder. There are now two published pilot studies suggesting efficacy, particularly in symptoms of irritability. This study aimed to explore if N-acetyl cysteine is a useful treatment for autistic disorder.

METHOD: This was a placebo-controlled, randomised clinical trial of 500&thinsp;mg/day oral N-acetyl cysteine over 6&thinsp;months, in addition to treatment as usual, in children with a Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision diagnosis of autistic disorder. The study was conducted in Victoria, Australia. The primary outcome measures were the Social Responsiveness Scale, Children's Communication Checklist-Second Edition and the Repetitive Behavior Scale-Revised. Additionally, demographic data, the parent-completed Vineland Adaptive Behavior Scales, Social Communication Questionnaire and clinician-administered Autism Diagnostic Observation Schedule were completed.

RESULTS: A total of 102 children were randomised into the study, and 98 (79 male, 19 female; age range: 3.1-9.9&thinsp;years) attended the baseline appointment with their parent/guardian, forming the Intention to Treat sample. There were no differences between N-acetyl cysteine and placebo-treated groups on any of the outcome measures for either primary or secondary endpoints. There was no significant difference in the number and severity of adverse events between groups.

CONCLUSION: This study failed to demonstrate any benefit of adjunctive N-acetyl cysteine in treating autistic disorder. While this may reflect a true null result, methodological issues particularly the lower dose utilised in this study may be confounders.

Strategies which aim to positively impact on weight, physical activity, diet and sedentary behaviours in children from zero to five years. A systematic review of the literature

Preventing the development of obesity in children is an international health priority. To assess the effectiveness of interventions designed to prevent obesity, promote healthy eating and/or physical activity and/or to reduce sedentary behaviours in 0–5-year-old children, a systematic review of the literature was performed. Literature searches were limited to articles published between January 1995 and June 2006, printed in English and sampling children aged 0–5-years. Searches excluded literature concerned with breastfeeding, eating disorders, and interventions which were school-based or concerned with obesity treatment. Two reviewers independently extracted data and assessed study strengths and weaknesses. Nine included studies were grouped based on the settings in which they were delivered. Most studies involved multi-approach interventions, were conducted in the USA and varied in study designs and quality. All showed some level of effectiveness on at least one obesity-behaviour in young children. These studies support, at a range of levels, the premise that parents are receptive to and capable of some behavioural changes that may promote healthy weight in their young children. The small quantity of research heralds the need, particularly given the potential for early intervention to have long-lasting impacts on individual and population health, to build in a substantial way upon this evidence base.

Weight, physical activity and dietary behavior change in young mothers : short term results of the HeLP-her cluster randomized controlled trial

Background
Preventing weight gain rather than treating established obesity is an important economic and public health response to the rapidly increasing rates of obesity worldwide. Treatment of established obesity is complex and costly requiring multiple resources. Preventing weight gain potentially requires fewer resources to reach broad population groups, yet there is little evidence for successful interventions to prevent weight gain in the community. Women with children are an important target group because of high rates of weight gain and the potential to influence the health behaviors in family members.

Methods
The aim of this cluster randomized controlled trial was to evaluate the short term effect of a community-based self-management intervention to prevent weight gain. Two hundred and fifty mothers of young children (mean age 40 years ± 4.5, BMI 27.9 kg/m2 ± 5.6) were recruited from the community in Melbourne, Australia. The intervention group (n = 127) attended four interactive group sessions over 4 months, held in 12 local primary schools in 2006, and was compared to a group (n = 123) receiving a single, non-interactive, health education session. Data collection included self-reported weight (both groups), measured weight (intervention only), self-efficacy, dietary intake and physical activity.

Results
Mean measured weight decreased significantly in the intervention group (-0.78 kg 95% CI; -1.22 to -0.34, p < 0.001). Comparing groups using self-reported weight, both the intervention and comparison groups decreased weight, -0.75 kg (95% CI; -1.57 to 0.07, p = 0.07) and -0.72 kg (95% CI; -1.59 to 0.14 p = 0.10) respectively with no significant difference between groups (-0.03 kg, 95% CI; -1.32 to 1.26, p = 0.95). More women lost or maintained weight in the intervention group. The intervention group tended to have the greatest effect in those who were overweight at baseline and in those who weighed themselves regularly. Intervention women who rarely self-weighed gained weight (+0.07 kg) and regular self-weighers lost weight (-1.66 kg) a difference of -1.73 kg (95% CI; -3.35 to -0.11 p = 0.04). The intervention reported increased physical activity although the difference between groups did not reach significance. Both groups reported replacing high fat foods with low fat alternatives and self-efficacy deteriorated in the comparison group only.

Conclusion
Both a single health education session and interactive behavioral intervention will result in a similar weight loss in the short term, although more participants in the interactive intervention lost or maintained weight. There were small non-significant changes to physical activity and changes to fat intake specifically replacing high fat foods with low fat alternatives such as fruit and vegetables. Self-monitoring appears to enhance weight loss when part of an intervention.