Cost-effectiveness of cognitive behavioural therapy and selective serotonin reuptake inhibitors for major depression in children and adolescents

Objective: To assess from a health sector perspective the incremental cost-effectiveness of cognitive behavioural therapy (CBT) and selective serotonin reuptake inhibitors (SSRIs) for the treatment of major depressive disorder (MDD) in children and adolescents, compared to 'current practice'. Method: The health benefit is measured as a reduction in disability-adjusted life years (DALYs), based on effect size calculations from meta-analysis of randomised controlled trials. An assessment on second stage filter criteria ('equity'; 'strength of evidence', 'feasibility' and 'acceptability to stakeholders') is also undertaken to incorporate additional factors that impact on resource allocation decisions. Costs and benefits are tracked for the duration of a new episode of MDD arising in eligible children (age 6-17 years) in the Australian population in the year 2000. Simulation-modelling techniques are used to present a 95% uncertainty interval (UI) around the cost-effectiveness ratios. Results: Compared to current practice, CBT by public psychologists is the most cost-effective intervention for MDD in children and adolescents at A$9000 per DALY saved (95% UI A$3900 to A$24 000). SSRIs and CBT by other providers are less cost-effective but likely to be less than A$50 000 per DALY saved (> 80% chance). CBT is more effective than SSRIs in children and adolescents, resulting in a greater total health benefit (DALYs saved) than could be achieved with SSRIs. Issues that require attention for the CBT intervention include equity concerns, ensuring an adequate workforce, funding arrangements and acceptability to various stakeholders. Conclusions: Cognitive behavioural therapy provided by a public psychologist is the most effective and cost-effective option for the first-line treatment of MDD in children and adolescents. However, this option is not currently accessible by all patients and will require change in policy to allow more widespread uptake. It will also require 'start-up' costs and attention to ensuring an adequate workforce.

Effects of Perilipin (PLIN) Gene Variation on Metabolic Syndrome Risk and Weight Loss in Obese Children and Adolescents

Context: Genetic polymorphisms at the perilipin (PLIN) locus have been investigated for their potential utility as markers for obesity and metabolic syndrome (MS). We examined in obese children and adolescents (OCA) aged 7-14 yr the association of single-nucleotide polymorphisms (SNP) at the PLIN locus with anthropometric, metabolic traits, and weight loss after 20-wk multi-disciplinary behavioral and nutritional treatment without medication. Design: A total of 234 OCA [body mass index (BMI = 30.4 +/- 4.4 kg/m(2); BMI Z-score = 2.31 +/- 0.4) were evaluated at baseline and after intervention. We genotyped four SNPs (PLIN1 6209T -> C, PLIN4 11482G -> A, PLIN5 13041A -> G, and PLIN6 14995A -> T). Results: Allele frequencies were similar to other populations, PLIN1 and PLIN4 were in linkage disequilibrium (D` = 0.999; P < 0.001). At baseline, no anthropometric differences were observed, but minor allele A at PLIN4 was associated with higher triglycerides (111 +/- 49 vs. 94 +/- 42 mg/dl; P = 0.003), lower high-density lipoprotein cholesterol (40 +/- 9 vs. 44 +/- 10 mg/dl; P = 0.003) and higher homeostasis model assessment for insulin resistance (4.0 +/- 2.3 vs. 3.5 +/- 2.1; P +/- 0.015). Minor allele A at PLIN4 was associated with MS risk (age and sex adjusted) hazard ratio 2.4 (95% confidence interval = 1.1-4.9) for genotype GA and 3.5 (95% confidence interval = 1.2-9.9) for AA. After intervention, subjects carrying minor allele T at PLIN6 had increased weight loss (3.3 +/- 3.7 vs. 1.9 +/- 3.4 kg; P = 0.002) and increased loss of the BMI Z-score (0.23 +/- 0.18 vs. 0.18 +/- 0.15; P +/- 0.003). Due to group size, risk of by-chance findings cannot be excluded. Conclusion: The minor A allele at PLIN4 was associated with higher risk of MS at baseline, whereas the PLIN6 SNP was associated with better weight loss, suggesting that these polymorphisms may predict outcome strategies based on multidisciplinary treatment for OCA. (J Clin Endocrinol Metab 93: 4933-4940, 2008)

Analysis of the PTPN11 gene in idiopathic short stature children and Noonan syndrome patients

Background Mutations in the PTPN11 gene are the main cause of Noonan syndrome (NS). The presence of some NS features is a frequent finding in children with idiopathic short stature (ISS). These children can represent the milder end of the NS clinical spectrum and PTPN11 is a good candidate for involvement in the pathogenesis of ISS. Objective To evaluate the presence of mutations in PTPN11 in ISS children who presented NS-related signs and in well-characterized NS patients. Patients and methods We studied 50 ISS children who presented at least two NS-associated signs but did not fulfil the criteria for NS diagnosis. Forty-nine NS patients diagnosed by the criteria of van der Burgt et al. were used to assess the adequacy of these criteria to select patients for PTPN11 mutation screening. The coding region of PTPN11 was amplified by polymerase chain reaction (PCR), followed by direct sequencing. Results No mutations or polymorphisms were found in the coding region of the PTPN11 gene in ISS children. Nineteen of the 49 NS patients (39%) presented mutations in PTPN11. No single characteristic enabled us to distinguish between NS patients with or without PTPN11 mutations. Conclusion Considering that no mutations were found in the present cohort with NS-related signs, it is unlikely that mutations would be found in unselected ISS children. The van der Burgt et al. criteria are adequate in attaining NS diagnosis and selecting patients for molecular studies. Mutations in the PTPN11 gene are commonly involved in the pathogenesis of NS but are not a common cause of ISS.

Binge eating symptoms, diet composition and metabolic characteristics of obese children and adolescents

This study aimed to determine the occurrence of symptoms of binge eating (BE) among children and adolescents seeking treatment for their obesity, as well as to evaluate their diet composition and metabolic characteristics. The Binge Eating scale (BES) was answered by 128 children and adolescents (10.77 +/- 2.04 years, BMI 29.15 +/- 4.98 kg/m(2), BMI Z score 2.28 +/- 0.46, 53.91% pubescent), who were classified into two subgroups-binge eaters (score greater than or equal to IS points) and non-binge eaters (score lower than 18 points). Anthropometric data, body composition and Tanner stages were collected and dietary evaluation conducted. Blood pressure was determined, and glucose, lipid profile and insulin assays were performed. insulin resistance was determined using HOMA-IR. BE symptoms were present in 39.06% of patients. Carbohydrate intake in diet composition was significantly higher among binge eaters. Children with BE did not demonstrate significant dissimilar metabolic characteristics when compared to their counterparts without BE. Therefore, BE seems to be a prevalent problem among children and adolescents seeking help for their obesity. When associated with obesity, this eating behaviour can influence macronutrient consumption through increased carbohydrate intake. Further research would be valuable to verify the reproducibility of these findings. (c) 2007 Elsevier Ltd. All rights reserved.

Measurements of adipocity and high blood pressure among children and adolescents living in Belo Horizonte

Objective: To verify an association, if it exists, between obesity and blood pressure raised beyond the 90th percentile in children and adolescents, and to determine the measure of adiposity that best correlates with blood pressure in these subjects. Design: Cross-sectional study. Setting: A school-based study in Belo Horizonte, Brazil. Participants: We selected randomly 1,403 students, aged from 6 to 18 years, from 545,046 students attending 521 public and private schools. Those selected completed the study. Main measures of outcome: We recorded the weight, height, skin fold in the triceps, subscapular, and suprailiac areas, waist and hip circumference, body-mass index, and resting systolic and diastolic blood pressures using a mercury sphygmomanometer. Results: In univariate analyses, body mass index greater or lesser than 85th percentile, measurements of skin thickness in the subscapular and suprailiac areas, and the sum of all measurements of skinfold thickness, were associated with both systolic and diastolic measurements of blood pressure. After multivariate analyses that adjusted for all measurements of adiposity except itself, and age, race, and socioeconomic state, we found that the increased body mass index was associated with a 3.6-fold increased frequency of elevated systolic measurements of blood pressure, with 9596 confidence intervals from 2.2 to 5.8, and a 2.7-fold increased frequency of elevated measurements of diastolic blood pressure, with 95% confidence intervals from 1.9 to 4.0. Conclusions: Body-mass index serves as a better predictor of elevated blood pressure among children than do local measurements of adiposity.

Texture Image Analysis in Differentiating Malignant from Benign Adrenal Cortical Tumors in Children and Adults

Objective: To investigate the possible role of chromatin texture parameters, nuclear morphology, DNA ploidy and clinical functional status in discriminating benign from malignant adrenocortical tumors (ACT). Patients and Methods: Forty-eight cases of clinically benign (n=40) and clinically malignant (n=8) ACT with a minimum of 5-years` follow-up were evaluated for chromatin texture parameters (run length, standard deviation, configurable run length, valley, slope, peak and other 21 Markovian features that describe the distribution of the chromatin in the nucleus), nuclear morphology (nuclear area, nuclear perimeter, nuclear maximum and minumum diameter, nuclear shape), and DNA ploidy. Nuclear parameters were evaluated in Feulgen-stained 5 mu m paraffin-sections analyzed using a CAS 200 image analyzer. Results: Since ACTs present different biological features in children and adults, patients were divided into two groups: children (<= 15 years) and adults (>15 years). In the group of children DNA ploidy presented a marginal significance (p=0.05) in discriminating ACTs. None of the parameters discriminated between malignant and benign ACT in the adult group. Conclusion: ACTs are uncommon and definitive predictive criteria for malignancy remain uncertain, particularly in children. Our data point to DNA content evaluated by image analysis as a new candidate tool for this challenging task. Texture image analysis did not help to differentiate malignant from benign adrenal cortical tumors in children and adults.

Distribution of HDL-cholesterol and non-HDL-cholesterol in Brazilian children and adolescents - The Floripa study

Background and aims: HDL-cholesterol (HDL-C) and non-HDL-cholesterol (nHDL-C) are involved in atherosclerosis. The aim of this study was to determine the distribution of HDL-C and nHDL-C and its association with cardiovascular and socio-cultural variables in a pediatric Brazilian sample. Methods and results: Children and adolescents from Florianopolis were randomly selected and a structured questionnaire was administered, a physical examination was performed and a blood sample was collected. Enzymatic and Direct methods in vitro were used to determine the total cholesterol and HDL-cholesterol levels. The associations among HDL-C and nHDL-C and the described variables were tested by odds ratio and logistic regression. A total of 1009 individuals were examined. Based on the Brazilian criteria, 23% were classified with low levels of HDL-C and 25% with high levels of non-HDL-C. After multivariate analysis there were significant associations among low HDL-C and high C-reactive protein (OR, 3.3; 95% CI, 2.1-5.2), paternal tobacco use (OR, 1.5; 95% CI, 1.1-2.1), and high triceps-to-subscapular index (OR, 1.5; 95% CI, 1.1-2.2). There were also significant associations among high nHDL-C and high waist circumference (OR, 1.95; 95% CI, 1.16-3.29), black skin color (OR, 1.78; 95% CI, 1.06-3.06), and high income (OR, 1.48; 95% CI, 1.09-2.02). Conclusions: In this sample, low levels of HDL-C were associated with other clinical variables such as a centripetal fat pattern and C-reactive protein, and n-HDL-C was associated with abdominal obesity, skin color and economic class. (C) 2009 Elsevier B. V. All rights reserved.

Acquisition of Serum Antibodies Reactive With Enterohemorrhagic Escherichia coli Virulence-Associated Factors by Healthy Brazilian Children and Adults

Background: Patients with hemorrhagic colitis or hemolytic uremic syndrome due to enterohemorrhagic Escherichia coli (EHEC) develop serum IgM and IgG response to lipopolysaccharide (LPS) and to virulence factors such as intimin. The small numbers of cases of diarrhea associated with EHEC strains in Brazil suggests a pre-existing immunity probably due to previous contact with diarrheagenic E. coli. Our aim was to evaluate the development of the serum antibody repertoire to EHEC virulence factors in Brazilian children and adults. Methods: Serum IgM and IgG antibodies were determined by enzyme-linked immunosorbent assay with LPS O111, LPS O26, and LPS O157 in 101 children between 2 months and 10 years of age and in 100 adult sera, by immunoblotting with protein membrane extracts and purified beta intimin; the ability of adult sera to neutralize Shiga toxin2 was also investigated. Results: Children older than 24 months had IgM concentrations reactive with the 3 LPS equivalent to those seen in the adult group, and significantly higher than the group of younger children (P < 0.05). Anti-O26 and anti-O157 LPS IgG concentrations were equivalent between the 2 groups of children and were significantly different from the adult group (P < 0.05). The anti-O111 LPS IgG levels in older children were intermediate between the younger group, and adults (P < 0.05). Immunoblotting revealed strong protein reactivity, including the conserved and variable regions of beta intimin and more than 50% of the adult samples neutralized Shiga toxin 2. Conclusions: Our results demonstrate an increasing anti-LPS and antiprotein antibody response with age, which could provide protection against EHEC infections.

Child psychiatry takes to the streets: A developmental partnership between a university institute and children and adolescents from the streets of Sao Paulo, Brazil

Objective: High levels of domestic violence, mental illness, and alienation from authorities are associated with high incidence of children/adolescents living on the streets in low and middle income countries. The Equilibrium Project (Programa Equilibrio) was created to facilitate social reintegration through a virtual partnership between an academic psychiatric institute and highly vulnerable children and adolescents living on the streets, in group shelter with supervision, and in other high risk situations. Methods: Descriptive presentation of qualitative data and analysis of preliminary empirical data collected over a 24-month period. Results: Dialogue between academic professionals, street children, and city officials shaped The Equilibrium Project over the last 2 years. The program has progressively moved from a professional clinic setting to a community-based but protected activity center with recreational and professional services and an emphasis on linkage with social service agencies, city government and law enforcement officials in an academic research context. A total of 351 patients have been served of whom virtually all were neglected by their parents, 58.4% report physical or sexual abuse, 88.89% have been diagnosed with a psychiatric disorder, 40.4% drug use. After 2 years of operation, 63.5% (n = 223) successfully completed or continue in treatment and 34.8% (n = 122) were reunited with their families. Conclusions and Practice implications: Program development guided by consumer input led to a successful program offering professional services in a protected community setting that facilitates social reintegration by providing ""go between"" services integrating relationships between alienated consumers and formal psychiatric, pediatric, social service, and criminal justice systems. (C) 2011 Elsevier Ltd. All rights reserved.

Distinct resistance mutation and polymorphism acquisition in HIV-1 protease of subtypes B and F1 from children and adult patients under virological failure

The goal of this work was to compare the differences between human immunodeficiency Virus type 1 (HIV-1) of B and F1 Subtypes in the acquisition of major and rninot- protease inhibitor (P1)-associated resistance mutations and of other polymorphisms at the protease (PR) gene, through a cross sectional Study. PR sequences from subtypes B and F1 isolates matched according to P1 exposure time from Brazilian patients were included in this study. Sequences were separated in four groups: 24 and 90 from children and 141 and 99 from adults infected with isolates of subtypes F1 and B, respectively. For comparison, 211 subype B and 79 subtype F1 PR sequences from drug-naive individuals Were included. Demographic and clinical data were similar among B- and F1-infected patients. In untreated patients, Mutations L1OV, K20R, and M361 were more frequent in subtype F1, while L63P, A7IT, and V771 were more prevalent in Subtype B. In treated patients, K20M, D30N, G73S, 184V, and L90M, were More prevalent in subtype B, and K20T and N88S Were more prevalent in Subtype F1. A higher proportion of subtype F1 than Of subtype B Strains Containing other polymorphisms was observed. V82L mutation was Present With increased frequency in isolates from children compared to isolates from adults infected with both subtypes. We could observe a faster resistance emergence in children than in adults, during treatment with protease inhibitors. This data provided evidence that, although rates of overall drug resistance do not differ between subtypes B and F1, the former accumulates resistance at higher proportion in specific amino acid positions of protease when compared to the latter. (c) 2008 Elsevier B.V. All rights reserved.

Myocarditis in children and detection of viruses in myocardial tissue: Implications for immunosuppressive therapy

Background: There is scarce information on the potential benefits of immunosuppression in children with myocarditis and viral genomes in myocardium. We investigated the occurrence of myocarditis in children with a preliminary diagnosis of dilated cardiomyopathy, the frequency of cardiotropic viruses in the myocardium, and the response to immunosuppression. Methods: Thirty patients (nine months to 12 years) with left ventricular ejection fraction of 22.8 +/- 4.1% were subjected to right cardiac catheterization and endomyocardial biopsy. Specimens were analyzed for the presence of inflammatory elements (Dallas criteria) and viral genome (polymerase chain reaction). Patients with active myocarditis received immunosuppressants (azatioprine and prednisone) and were recatheterized nine months later. A historical control group of nine patients with myocarditis who did not receive immunosuppressants was included. Results: Active myocarditis was diagnosed in ten patients (five with viral genomes detected). Immunosuppression resulted in a significant increase in left ventricular ejection fraction from 25.2 +/- 2.8% to 45.7 +/- 8.6% (versus 20.0 +/- 4.0% to 22.0 +/- 9.0% in historical controls, p < 0.01) and cardiac index from 3.28 +/- 0.51 L/min/m(2) to 4.40 +/- 0.49 L/min/m(2) (versus 3.50 +/- 0.40 L/min/m(2) to 3.70 +/- 0.50 L/min/m(2) in controls, p < 0.01), regardless of the presence of viral genomes (p - 0.98 and p - 0.22, respectively for the two variables). No relevant clinical events were observed. Non-inflammatory cardiomyopathy was diagnosed in 20 patients (seven with viral genomes). While on conventional therapy, there were four deaths and three assignments to transplantation, and no improvement of left ventricular ejection fraction in the remaining ones (22.5 +/- 3.6% to 27.5 +/- 10.6%). Conclusion: Children with chronic myocarditis seem to benefit from immunosuppressive therapy, regardless of the presence of viral genome in the myocardium. (C) 2009 Elsevier Ireland Ltd. All rights reserved.

A description of adaptive and maladaptive behaviour in children and adolescents with Cri-du-chat syndrome

Background Psychological tests can be useful to record adaptive and maladaptive behaviours of children with intellectual disability. The objective of this study was to describe the adaptive and maladaptive behaviour of children and adolescents with Cri-du-chat syndrome. Methods The sample consisted of 10 children and adolescents with Cri-du-chat syndrome (mean chronological age = 11.3 years, mean mental age = 18 months). The developmental quotient was calculated through the Psychoeducational Profile - Revised. An observational protocol was used to record adaptive and maladaptive behaviours. Results The number of maladaptive behaviours observed was different among participants. However, all of them had high rates of adaptive behaviours, such as rule-following. Conclusions These results, though preliminary, justify that we continue to think about the need for psychoeducational interventions aimed at stimulating the repertoire of adaptive behaviours, in people with Cri-du-chat syndrome.