Cost-effectiveness analysis of universal childhood hepatitis A vaccination in Brazil: Regional analyses according to the endemic context

Objective: To To conduct a cost-effectiveness analysis of a universal childhood hepatitis A vaccination program in Brazil. Methods: An age and time-dependent dynamic model was developed to estimate the incidence of hepatitis A for 24 years. The analysis was run separately according to the pattern of regional endemicity, one for South + Southeast (low endemicity) and one for the North + Northeast + Midwest (intermediate endemicity). The decision analysis model compared universal childhood vaccination with current program of vaccinating high risk individuals. Epidemiologic and cost estimates were based on data from a nationwide seroprevalence survey of viral hepatitis, primary data collection, National Health Information Systems and literature. The analysis was conducted from both the health system and societal perspectives. Costs are expressed in 2008 Brazilian currency (Real). Results: A universal immunization program would have a significant impact on disease epidemiology in all regions, resulting in 64% reduction in the number of cases of icteric hepatitis, 59% reduction in deaths for the disease and a 62% decrease of life years lost, in a national perspective. With a vaccine price of R$16.89 (US$7.23) per dose, vaccination against hepatitis A was a cost-saving strategy in the low and intermediate endemicity regions and in Brazil as a whole from both health system and society perspective. Results were most sensitive to the frequency of icteric hepatitis, ambulatory care and vaccine costs. Conclusions: Universal childhood vaccination program against hepatitis A could be a cost-saving strategy in all regions of Brazil. These results are useful for the Brazilian government for vaccine related decisions and for monitoring population impact if the vaccine is included in the National Immunization Program. (C) 2012 Elsevier Ltd. All rights reserved.

Fc gamma Receptor Gene Polymorphisms in Childhood Immune Thrombocytopenic Purpura

Immune thrombocytopenic purpura (ITP) is a common hematological disorder in the childhood, and it is one of the most common forms of autoimmune disease in pediatric patients. The ITP basis is a primary dysfunction of the immune system. This study aimed to analyze the genetic polymorphisms of the Fc gamma receptors IIA and IIIA. The genetic polymorphisms of the Fc receptors gamma IIA (131H/R) and gamma RIIIA (158V/F) were analyzed by polymerase chain reaction-restriction fragment length polymorphism technique. Odds ratio and 95% confidence interval were calculated by chi(2) test. Homozygous polymorphic genotype for the Fc gamma RIIIA was significantly more frequent among patients compared with controls (odds ratio = 0.27; 95% confidence interval, 0.09-0.80; P = 0.03). There was no statistical difference between the ITP group and the controls in the analysis of combinations of alleles of the high-affinity Fc receptor, but the ITP individuals with this combination had a lower duration of disease (P = 0.01). Genetic polymorphisms in immune system genes can be important for ITP pathogenesis and disease outcome.

THE ASSOCIATION BETWEEN CHILDHOOD ADVERSITY AND COMPONENTS OF METABOLIC SYNDROME IN ADULTS WITH MOOD DISORDERS: RESULTS FROM THE INTERNATIONAL MOOD DISORDERS COLLABORATIVE PROJECT

Objective: We sought to determine whether a reported history of childhood adversity is associated with components of the National Cholesterol Education Program Adult Treatment Panel III (NCEP-ATP-III)-defined metabolic syndrome in adults with mood disorders. Method: This was a cross-sectional analysis of adult outpatients (N = 373; n = 230 female, n = 143 male; mean age [SD] = 42.86 [14.43]) from the International Mood Disorders Collaborative Project (University of Toronto and Cleveland Clinic) with DSM-IV-defined major depressive disorder and bipolar I/II disorder. Childhood adversity was measured with the Klein Trauma & Abuse-Neglect self-report scale. The groups with and without childhood adversity were compared to determine possible differences in the rates of metabolic syndrome and its components. Logistic and linear regressions adjusted for age, sex, education, employment status, and smoking were used to evaluate the association between childhood adversity and components of metabolic syndrome. Results: For the full sample, 83 subjects (22.25%) met criteria for metabolic syndrome. Individuals reporting a history of any childhood adversity had higher systolic and diastolic blood pressure (systolic: p = 0.040; diastolic: p = 0.038). Among subjects with a history of sexual abuse, a significant proportion met criteria for obesity (45.28% vs. 32.88%; p = 0.010); a trend toward overweight was found for subjects with a history of physical abuse (76.32% vs. 63.33%; p = 0.074), although this relationship did not remain significant after adjusting for potential confounders. There was no statistically significant difference in the overall rate of dyslipidemia and/or metabolic syndrome between subjects with and without childhood adversity. Conclusion: The results herein provide preliminary evidence suggesting that childhood adversity is associated with metabolic syndrome components in individuals with mood disorders. Int'l. J. Psychiatry in Medicine 2012;43:165-177)

Inactive Disease and Remission in Childhood-Onset Systemic Lupus Erythematosus

Objective. To define inactive disease (ID) and clinical remission (CR) and to delineate variables that can be used to measure ID/CR in childhood-onset systemic lupus erythematosus (cSLE). Methods. Delphi questionnaires were sent to an international group of pediatric rheumatologists. Respondents provided information about variables to be used in future algorithms to measure ID/CR. The usefulness of these variables was assessed in 35 children with ID and 31 children with minimally active lupus (MAL). Results. While ID reflects cSLE status at a specific point in time, CR requires the presence of ID for >6 months and considers treatment. There was consensus that patients in ID/CR can have <2 mild nonlimiting symptoms (i.e., fatigue, arthralgia, headaches, or myalgia) but not Raynaud's phenomenon, chest pain, or objective physical signs of cSLE; antinuclear antibody positivity and erythrocyte sedimentation rate elevation can be present. Complete blood count, renal function testing, and complement C3 all must be within the normal range. Based on consensus, only damage-related laboratory or clinical findings of cSLE are permissible with ID. The above parameters were suitable to differentiate children with ID/CR from those with MAL (area under the receiver operating characteristic curve >0.85). Disease activity scores with or without the physician global assessment of disease activity and patient symptoms were well suited to differentiate children with ID from those with MAL. Conclusion. Consensus has been reached on common definitions of ID/CR with cSLE and relevant patient characteristics with ID/CR. Further studies must assess the usefulness of the data-driven candidate criteria for ID in cSLE.

Integrating fundamental movement skills in late childhood

The study examined how children of different ages integrate fundamental movement skills, such as running and throwing, and whether their developmental status was related to the combination of these skills. Thirty children were divided into three groups (G1 = 6-year-olds, G2 = 9-year-olds, and G3 = 12-year-olds) and filmed performing three tasks: running, overarm throwing, and the combined task. Patterns were identified and described, and the efficiency of integration was calculated (distance differences of the ball thrown in two tasks, overarm throwing and combined task). Differences in integration were related to age: the 6-year-olds were less efficient in combining the two skills than the 9- and 12-year-olds. These differences may be indicative of a phase of integrating fundamental movement skills in the developmental sequence. This developmental status, particularly throwing, seems to be related to the competence to integrate skills, which suggests that fundamental movement skills may be developmental modules.

Differential MiRNA expression in childhood acute lymphoblastic leukemia and association with clinical and biological features

The present study aimed to analyze the expression profile of the microRNAs previously described as associated with childhood ALL, miR-92a, miR-100, miR-125a-5p, miR-128a, miR-181b, miR-196b and let-7e, and their association with biological/prognostic features in 128 consecutive samples of childhood acute lymphoblastic leukemia (ALL) by quantitative real-time PCR. A significant association was observed between higher expression levels of miR-196b and T-ALL, miR-100 and patients with low white blood cell count at diagnosis and t(12;21) positive ALL. These findings suggest a potential activity of these microRNAs in pediatric ALL biology. (C) 2011 Elsevier Ltd. All rights reserved.

CYP3A5 and NAT2 gene polymorphisms: role in childhood acute lymphoblastic leukemia risk and treatment outcome

Susceptibility to acute lymphoblastic leukemia can be highly influenced by genetic polymorphisms in metabolizing enzyme genes of environmental carcinogens. This study aimed to evaluate the impact of the CYP3A5 and NAT2 metabolizing enzyme polymorphisms on the risk of childhood acute lymphoblastic leukemia. The analysis was conducted on 204 ALL patients and in 364 controls from a Brazilian population, using PCR-RFLP. The CYP3A5*3 polymorphic homozygous genotype was more frequent among ALL patients and the *3 allele variant was significantly associated with increased risk of childhood ALL (OR = 0.29; 95% CI, 0.14-0.60). The homozygous polymorphic genotype for the *6 allele variant was extremely rare and found in only two individuals. The heterozygous frequencies were similar for the ALL group and the control group. No significant differences were observed between the groups analyzed regarding NAT2 variant polymorphisms. None of the polymorphisms analyzed was related to treatment outcome. The results suggest that CYP3A5*3 polymorphism may play an important role in the risk of childhood ALL.

Impact of benign childhood epilepsy with centrotemporal spikes (BECTS) on school performance

BECTS represents the vast majority of childhood focal epilepsy. Owing to the age peculiarity of children who suffer from this disease, i.e., school-going age of between 6 and 9 years, the condition is often referred to as a school disorder by parents and teachers. Objective: The aim of this study was to evaluate the academic performance of children with BED'S, according to the clinical and electroencephalographic ILAE criteria, and compare the results of neuropsychological tests of language and attention to the frequency of epileptic discharges. Methods: The performances of 40 school children with BED'S were evaluated by applying a school performance test (SBT), neuropsychological tests (WISC and Trail-Making), and language tests (Illinois Test Psycholinguistic Abilities - ITPA - and Staggered Spondaic Word - SSW). The same tests were applied in the control group. Results: Children with BED'S, when compared to those in the control group, showed lower scores in academic performance (SPT), digits and similarities subtests of WISC, auditory processing subtest of SSW, and ITPA - representational and automatic level. The study showed that epileptic discharges did not influence the results. Conclusion: Children with BED'S scored significantly lower scores in tests on academic performance, when compared with those in the control group probably due to executive dysfunction. (C) 2011 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.

Expression profile of apoptosis-related genes in childhood adrenocortical tumors: low level of expression of BCL2 and TNF genes suggests a poor prognosis

Background: Impaired apoptosis has been implicated in the development of childhood adrenocortical tumors (ACT), although the expression of apoptosis-related gene expression in such tumors has not been reported. Methods: The mRNA expression levels of the genes CASP3, CASP8, CASP9, FAS, TNF, NFKB, and BCL2 were analyzed by quantitative real-time PCR in consecutive tumor samples obtained at diagnosis from 60 children with a diagnosis of ACT and in 11 non-neoplastic adrenal samples. BCL2 and TNF protein expression was analyzed by immunohistochemistry. Results: A significant association was observed between tumor size >= 100 g and lower expression levels of the BCL2 (P=0.03) and TNF (P=0.05) genes; between stage IV and lower expression levels of CASP3 (P=0.008), CASP9 (P=0.02), BCL2 (P=0.002), TNF (P=0.05), and NFKB (P=0.03); Weiss score >= 3 and lower expression of TNF (P=0.01); unfavorable event and higher expression values of CASP9 (P=0.01) and lower values of TNF (P=0.02); and death and lower expression of BCL2 (P=0.04). Underexpression of TNF was associated with lower event-free survival in uni- and multivariate analyses (P<0.01). Similar results were observed when patients with Weiss score <3 were excluded. Conclusion: This study supports the participation of apoptosis-related genes in the biology and prognosis of childhood ACT and suggests the complex role of these genes in the pathogenesis of this tumor.

Orbital Hemangiopericytoma/Solitary Fibrous Tumor in Childhood

A 12-year-old girl had a 6-year history of a large soft-tissue mass in her left orbit. The tumor biopsy was previously performed elsewhere when she was 7 years old, but no treatment was offered at that time. Later, the tumor was completely excised, and histologic examination revealed a mesenchymal neoplasia with typical hemangiopericytoma features. At 9 months of follow up, no evidence of local recurrence or metastasis was seen.

Impact of pretransplant minimal residual disease after cord blood transplantation for childhood acute lymphoblastic leukemia in remission: an Eurocord, PDWP-EBMT analysis

To address the prognostic value of minimal residual disease (MRD) before unrelated cord blood transplantation (UCBT) in children with acute lymphoblastic leukemia (ALL), we analyzed 170 ALL children transplanted in complete remission (CR) after myeloablative conditioning regimen. In all, 72 (43%) were in first CR (CR1), 77 (45%) in second CR (CR2) and 21 (12%) in third CR (CR3). The median interval from MRD quantification to UCBT was 18 days. All patients received single-unit UCBT. Median follow-up was 4 years. Cumulative incidence (CI) of day-60 neutrophil engraftment was 85%. CI of 4 years relapse was 30%, incidence being lower in patients with negative MRD before UCBT (hazard ratio (HR) = 0.4, P = 0.01) and for those transplanted in CR1 and CR2 (HR = 0.3, P = 0.002). Probability of 4 years leukemia-free survival (LFS) was 44%, (56, 44 and 14% for patients transplanted in CR1, CR2 and CR3, respectively (P = 0.0001)). Patients with negative MRD before UCBT had better LFS after UCBT compared with those with positive MRD (54% vs 29%; HR = 2, P = 0.003). MRD assessment before UCBT for children with ALL in remission allows identifying patients at higher risk of relapse after transplantation. Approaches that may decrease relapse incidence in children given UCBT with positive MRD should be investigated to improve final outcomes. Leukemia (2012) 26, 2455-2461; doi:10.1038/leu.2012.123

Teaching of the Integrated Management of Childhood Illness strategy in undergraduate nursing programs

Objective: To describe and analyze the teaching of the Integrated Management of hildhood Illness (IMCI) strategy on Brazilian undergraduate nursing programs. Method: Integrating an international multicentric study, a cross-sectional online survey was conducted between May and October 2010 with 571 undergraduate nursing programs in Brazil Results: Responses were received from 142 programs, 75% private and 25% public. 64% of them included the IMCI strategy in the theoretical content, and 50% of the programs included IMCI as part of the students’ practical experience. The locations most used for practical teaching were primary health care units. The ‘treatment’ module was taught by the fewest number of programs, and few programs had access to the IMCI instructional manuals. All programs used exams for evaluation, and private institutions were more likely to include class participation as part of the evaluation. Teaching staff in public institutions were more likely to have received training in teaching IMCI. Conclusion: In spite of the relevance of the IMCI strategy in care of the child, its content is not addressed in all undergraduate programs in Brazil, and many programs do not have access to the IMCI teaching manuals and have not provide training in IMCI to their teaching staff.

Influence of psychosocial risk factors on the trajectory of mental health problems from childhood to adolescence: a longitudinal study

Background Longitudinal epidemiological studies involving child/adolescent mental health problems are scarce in developing countries, particularly in regions characterized by adverse living conditions. We examined the influence of psychosocial factors on the trajectory of child/adolescent mental health problems (CAMHP) over time. Methods A population-based sample of 6- to 13-year-olds with CAMHP was followed-up from 2002–2003 (Time 1/T1) to 2007–2008 (Time 2/T2), with 86 out of 124 eligible children/adolescents at T1 being reassessed at T2 (sample loss: 30.6%). Outcome: CAMHP at T2 according to the Child Behavior Checklist/CBCL’s total problem scale. Psychosocial factors: T1 variables (child/adolescent’s age, family socioeconomic status); trajectory of variables from T1 to T2 (child/adolescent exposure to severe physical punishment, mother exposure to severe physical marital violence, maternal anxiety/depression); and T2 variables (maternal education, child/adolescent’s social support and pro-social activities). Results Multivariate analysis identified two risk factors for child/adolescent MHP at T2: aggravation of child/adolescent physical punishment and aggravation of maternal anxiety/depression. Conclusions The current study shows the importance of considering child/adolescent physical punishment and maternal anxiety/depression in intervention models and mental health care policies.

Exercise training in childhood-onset systemic lupus erythematosus: a controlled randomized trial

Abstract Introduction Exercise training has emerged as a promising therapeutic strategy to counteract physical dysfunction in adult systemic lupus erythematosus. However, no longitudinal studies have evaluated the effects of an exercise training program in childhood-onset systemic lupus erythematosus (C-SLE) patients. The objective was to evaluate the safety and the efficacy of a supervised aerobic training program in improving the cardiorespiratory capacity in C-SLE patients. Methods Nineteen physically inactive C-SLE patients were randomly assigned into two groups: trained (TR, n = 10, supervised moderate-intensity aerobic exercise program) and non-trained (NT, n = 9). Gender-, body mass index (BMI)- and age-matched healthy children were recruited as controls (C, n = 10) for baseline (PRE) measurements only. C-SLE patients were assessed at PRE and after 12 weeks of training (POST). Main measurements included exercise tolerance and cardiorespiratory measurements in response to a maximal exercise (that is, peak VO2, chronotropic reserve (CR), and the heart rate recovery (ΔHRR) (that is, the difference between HR at peak exercise and at both the first (ΔHRR1) and second (ΔHRR2) minutes of recovery after exercise). Results The C-SLE NT patients did not present changes in any of the cardiorespiratory parameters at POST (P > 0.05). In contrast, the exercise training program was effective in promoting significant increases in time-to-exhaustion (P = 0.01; ES = 1.07), peak speed (P = 0.01; ES = 1.08), peak VO2 (P = 0.04; ES = 0.86), CR (P = 0.06; ES = 0.83), and in ΔHRR1 and ΔHRR2 (P = 0.003; ES = 1.29 and P = 0.0008; ES = 1.36, respectively) in the C-SLE TR when compared with the NT group. Moreover, cardiorespiratory parameters were comparable between C-SLE TR patients and C subjects after the exercise training intervention, as evidenced by the ANOVA analysis (P > 0.05, TR vs. C). SLEDAI-2K scores remained stable throughout the study. Conclusion A 3-month aerobic exercise training was safe and capable of ameliorating the cardiorespiratory capacity and the autonomic function in C-SLE patients. Trial registration NCT01515163.