Abatacept in children with juvenile idiopathic arthritis: a randomised, double-blind, placebo-controlled withdrawal trial

Background Some children with juvenile idiopathic arthritis either do not respond, or are intolerant to, treatment with disease-modifying antirheumatic drugs, including anti-tumour necrosis factor (TNF) drugs. We aimed to assess the safety and efficacy of abatacept, a selective T-cell costimulation modulator, in children with juvenile idiopathic arthritis who had failed previous treatments.Methods We did a double-blind, randomised controlled withdrawal trial between February, 2004, and June, 2006. We enrolled 190 patients aged 6-17 years, from 45 centres, who had a history of active juvenile idiopathic arthritis; at least five active joints; and an inadequate response to, or intolerance to, at least one disease-modifying antirheumatic drug. All 190 patients were given 10 mg/kg of abatacept intravenously in the open-label period of 4 months. of the 170 patients who completed this lead-in course, 47 did not respond to the treatment according to predefined American College of Rheumatology (ACR) paediatric criteria and were excluded. of the patients who did respond to abatacept, arthritis, and 62 were randomly assigned to receive placebo at the same dose and timing. The primary endpoint was time to flare of arthritis. Flare was defined as worsening of 30% or more in at least three of six core variables, with at least 30% improvement in no more than one variable. We analysed all patients who were treated as per protocol. This trial is registered, number NCT00095173.Findings Flares of arthritis occurred in 33 of 62 (53%) patients who were given placebo and 12 of 60 (20%) abatacept patients during the double-blind treatment (p=0.0003). Median time to flare of arthritis was 6 months for patients given placebo (insufficient events to calculate IQR); insufficient events had occurred in the abatacept group for median time to flare to be assessed (p=0.0002). The risk of flare in patients who contined abatacept was less than a third of that for controls during that double-blind period (hazard ratio 0.31, 95% CI 0.16-0.95). During the double-blind period, the frequency of adverse events did not differ in the two treatment groups, Adverse events were recorded in 37 abatacept recipients (62%) and 34 (55%) placebo recipients (p=0.47); only two serious adverse events were reported, bouth in controls (p=0.50).Interpretation Selective modulation of T-cell costimulation with abatacept is a rational alternative treatment for children with juvenile idiopathic arthritis.Funding Bristol-Myers Squibb.

Static balance and function in children with cerebral palsy submitted to neuromuscular block and neuromuscular electrical stimulation: Study protocol for prospective, randomized, controlled trial

Background: The use of botulinum toxin A (BT-A) for the treatment of lower limb spasticity is common in children with cerebral palsy (CP). Following the administration of BT-A, physical therapy plays a fundamental role in potentiating the functionality of the child. The balance deficit found in children with CP is mainly caused by muscle imbalance (spastic agonist and weak antagonist). Neuromuscular electrical stimulation (NMES) is a promising therapeutic modality for muscle strengthening in this population. The aim of the present study is to describe a protocol for a study aimed at analyzing the effects of NMES on dorsiflexors combined with physical therapy on static and functional balance in children with CP submitted to BT-A.Methods/Design: Protocol for a prospective, randomized, controlled trial with a blinded evaluator. Eligible participants will be children with cerebral palsy (Levels I, II and III of the Gross Motor Function Classification System) between five and 12 years of age, with independent gait with or without a gait-assistance device. All participants will receive BT-A in the lower limbs (triceps surae). The children will then be randomly allocated for either treatment with motor physical therapy combined with NMES on the tibialis anterior or motor physical therapy alone. The participants will be evaluated on three occasions: 1) one week prior to the administration of BT-A; 2) one week after the administration of BT-A; and 3) four months after the administration of BT-A (end of intervention). Spasticity will be assessed by the Modified Ashworth Scale and Modified Tardieu Scale. Static balance will be assessed using the Medicapteurs Fusyo pressure platform and functional balance will be assessed using the Berg Balance Scale.Discussion: The aim of this protocol study is to describe the methodology of a randomized, controlled, clinical trial comparing the effect of motor physical therapy combined with NMES on the tibialis anterior muscle or motor physical therapy alone on static and functional balance in children with CP submitted to BT-A in the lower limbs. This study describes the background, hypotheses, methodology of the procedures and measurement of the results.

Effect of posture-control insoles on function in children with cerebral palsy: Randomized controlled clinical trial

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Alterations of cell-mediated immune response in children with febrile seizures

The aim of the present investigation was to study the distribution of T-cell subsets in peripheral blood defined by monoclonal antibodies and by the lymphocyte proliferative response to phytohemagglutinin (PHA) in 30 children with febrile seizures and in 14 age-matched control subjects. Frequent respiratory, urinary and dermatologic infections were observed in 22 patients. The immunologic parameters showed that 64% of the patients presented an increased number of CD8+ cells and a low helper/suppressor ratio was observed in 60% of the patients. In addition, the proliferative response of lymphocytes to PHA was impaired in the patients It was observed the presence of inhibitory activity on lymphocyte function in the plasma of 33% of children with febrile seizures. These results suggest that patients with febrile seizures have an impairment of cellular immunity that may be connected with this epileptic syndrome and explain the infections observed.

Acute and sustained effects of early administration of inhaled nitric oxide to children with acute respiratory distress syndrome

OBJECTIVE: To determine the acute and sustained effects of early inhaled nitric oxide on some oxygenation indexes and ventilator settings and to compare inhaled nitric oxide administration and conventional therapy on mortality rate, length of stay in intensive care, and duration of mechanical ventilation in children with acute respiratory distress syndrome. DESIGN: Observational study. SETTING: Pediatric intensive care unit at a university-affiliated hospital. PATIENTS: Children with acute respiratory distress syndrome, aged between 1 month and 12 yrs. INTERVENTIONS: Two groups were studied: an inhaled nitric oxide group (iNOG, n = 18) composed of patients prospectively enrolled from November 2000 to November 2002, and a conventional therapy group (CTG, n = 21) consisting of historical control patients admitted from August 1998 to August 2000. MEASUREMENTS AND MAIN RESULTS: Therapy with inhaled nitric oxide was introduced as early as 1.5 hrs after acute respiratory distress syndrome diagnosis with acute improvements in Pao(2)/Fio(2) ratio (83.7%) and oxygenation index (46.7%). Study groups were of similar ages, gender, primary diagnoses, pediatric risk of mortality score, and mean airway pressure. Pao(2)/Fio(2) ratio was lower (CTG, 116.9 +/- 34.5; iNOG, 62.5 +/- 12.8, p <.0001) and oxygenation index higher (CTG, 15.2 [range, 7.2-32.2]; iNOG, 24.3 [range, 16.3-70.4], p <.0001) in the iNOG. Prolonged treatment was associated with improved oxygenation, so that Fio(2) and peak inspiratory pressure could be quickly and significantly reduced. Mortality rate for inhaled nitric oxide-patients was lower (CTG, ten of 21, 47.6%; iNOG, three of 18, 16.6%, p <.001). There was no difference in intensive care stay (CTG, 10 days [range, 2-49]; iNOG, 12 [range, 6-26], p >.05) or duration of mechanical ventilation (TCG, 9 days [range, 2-47]; iNOG, 10 [range, 4-25], p >.05). CONCLUSIONS: Early treatment with inhaled nitric oxide causes acute and sustained improvement in oxygenation, with earlier reduction of ventilator settings, which might contribute to reduce the mortality rate in children with acute respiratory distress syndrome. Length of stay in intensive care and duration of mechanical ventilation are not changed. Prospective trials of inhaled nitric oxide early in the setting of acute lung injury in children are needed.

Arbitrarily primed polymerase chain reaction for fingerprinting the genotype identification of mutans streptococci in children with Down syndrome

This study investigated the possible intrafamilial similarity of mutans streptococcal strains in some families with a child with Down syndrome using chromosomal DNA fingerprinting. The isolates were genotyped using arbitrarily primed polymerase chain reaction with the OPA 02 and OPA 03 primers. The results showed that five children with Down syndrome harbored mutans streptococci genotypes different from those of their mothers. A matching of genotypes was observed within the control pair (mother/child without Down syndrome). After six months, new samples were collected from all participants. Analysis showed that samples from children with Down syndrome were colonized by a new strain of Streptococcus mutans that did not match the previously collected one. The results suggest the S. mutans indigenous bacteria change more than once in children with Down syndrome.

Occurrence of Actinobacillus actinomycetemcomitans in patients with chronic periodontitis, aggressive periodontitis, healthy subjects and children with gingivitis in two cities of the state of São Paulo, Brazil

The aim of this study was to determine the frequency of isolation of Actinobacillus actinomycetemcomitans (Aa) in 100 patients with chronic periodontitis, 14 patients with aggressive periodontitis, 142 pre-school children with gingivitis and 134 periodontally healthy subjects. Samples of subgingival plaque were taken using sterilized paper points introduced into periodontal pockets or gingival crevice for 60 seconds and inoculated on TSBV agar, which was incubated under anaerobiosis at 37°C, for 4 days. Microbial identification was performed through biochemical methods and morphocellular and morphocolonial analysis. Aa was detected in 40.3% of healthy subjects, 68% of patients with chronic periodontitis, 92.86% of patients with aggressive periodontitis and 40.14% of children with gingivitis. The rate of recovery of Aa in the tested human groups proved to be higher than previously reported and in agreement with participation of this facultative anaerobe as a member of native microbiota of the periodontium and its relation with aggressive and chronic periodontitis in Brazil.

Assessment of health-related quality of life in children with functional defecation disorders

Objective: To evaluate the health-related quality of life in children with functional defecation disorders. Methods: One hundred children seen consecutively were enrolled and subdivided into three subsets according to the Roma II classification criteria: functional constipation (n = 57), functional fecal retention (n = 29) and nonretentive functional soiling (n = 14). The generic instrument Child Health Questionnaire - Parent Form 50 (CHQ-PF50®), was used to measure quality of life and to assess the impact of these disorders from the point of view of parents. The instrument measures physical and psychosocial wellbeing in 15 health domains, each of which is graded on a scale from 0 to 100, with higher values indicating better health and greater wellbeing. Ten of these are then used to obtain two aggregated and summary scores: the physical and psychosocial scores. Results: No statistically significant differences were detected between subsets in terms of demographic or anthropometric characteristics. In 14 domains, children with defecation disorders scored lower than healthy children. When subsets were compared, statistically significant differences were detected between children with nonretentive functional soiling (lower scores) and those with functional constipation. Physical and psychosocial scores for the entire sample were lower than those for the group of healthy children used as controls. Conclusions: The CHQ-PF50® was considered adequate for demonstrating compromised quality of life in children with functional defecation disorders, as has been reported for other diseases, being a useful tool for making treatment decisions and for patient follow-up. Copyright © 2006 by Sociedade Brasileira de Pediatria.

Characterization of language disorders in children with lead poisoning

Background: lead poisoning can have a negative impact on the neuropsychological functions, including language, due to the damage it causes to the developthent of the Central Nervous System. Aim: to verify the occurrence of language disorders in children who suffered from led poisoning and to verify the correlation between the lead concentration level in the blood and the language disorders presented by the children. Method: language evaluation of 20 preschoolers, with lead concentration level in the blood above 10μg/dl. Results: 13 children presented language impairment involving only phonology or more than one language subsystem. The statistical analysis indicated that no correlation exists between the severity of the language impairment and the concentration levels of lead. Conclusion: the number of children with language impairment indicates lead poisoning as a risk factor for the present alterations, even though other risk factors for language disorders were found and the absence of correlation between the investigated variables.

Methotrexate improves the health-related quality of life of children with juvenile idiopathic arthritis

Objectives: To examine the change in health-related quality of life (HRQOL) and its determinants in children with juvenile idiopathic arthritis (JIA) treated with methotrexate (MTX). Methods: Patients were extracted from the PRINTO clinical trial which aimed to evaluate the efficacy and safety profile of MTX administered in standard, intermediate or higher doses (10, 15 and 30 mg/m2/week respectively). Children with polyarticular-course JIA, who were less than 18 years and had a complete HRQOL assessment were included. Results: A total of 521 children were included. At baseline, patients with JIA showed poorer HRQOL (p<0.01) than healthy children. In 207/412 (50%) and 63 (15%) children, HRQOL values were 2 standard deviations below the mean of healthy controls in the physical and psychosocial summary scale, respectively. After 6 months of treatment with standard dose MTX, there was a statistically significant improvement in all HRQOL health concepts, particularly the physical ones. Similar improvements were observed in those who did not respond to a standard dose of MTX and were subsequently randomised to a higher dose. The presence of marked disability at baseline was associated with a fivefold increased risk of retaining poor physical health after 6 months of active treatment with standard dose MTX. Other less important determinants of retaining poor physical well-being were the baseline level of systemic inflammation, pain intensity and an antinuclear-antibody-negative status. Conclusions: MTX treatment produces a significant improvement across a wide range of HRQOL components, particularly in the physical domains, in patients with JIA.

Therapeutic option for children with esophageal caustic stenosis

Caustic ingestion is a leading cause of esophageal stenosis in children. Herein we report four cases using mitomycin C (MMC), a drug that inhibits cell division, protein synthesis and fibroblast proliferation and has been used as an adjuvant therapy for caustic esophageal stenosis that is recalcitrant to conventional dilation techniques. A retrospective chart review was performed on four pediatric patients with severe, recurrent esophageal stricture after caustic ingestion. The patients had required six to 20 esophageal dilations over a 4-16-month period before MMC application. MMC was applied after an endoscopic dilation on saturated pledgets at a dose of 0.1 mg/mL for 2 min in the area where the strictures had been lyzed. From the four children treated with MMC, two have been asymptomatic for 16 and 20 months and two still require esophageal dilation, however, at longer intervals. All patients have shown satisfactory weight gain with food intake exclusively per oral. Although further studies are required, there is strong evidence that MMC is a safe and effective adjuvant therapy in the treatment of esophageal caustic stenosis. © 2008 The Authors.

Performance of children with learning difficulties in fine motor function and handwriting

This study aimed to compare and characterize the fine, sensory and perceptive function performance and handwriting quality between students with learning difficulties and students with good academic performance. Methods: This study comprised 192 students from 2nd to 4th grades, both genders, whose ages ranged from 7 to 11 years old. The students were distributed into: GI, GII, GIII and GIV, comprising 96 students with learning difficulties, and groups GV, GVI, GVII, GVIII comprising 96 students with good academic performance. The students were submitted to evaluation of fine motor, sensorial and perception functions and handwriting evaluation under dictation. Results: The results showed that the students with learning difficulties, from 1st to 3rd grade, had lower performance on tests of fine motor, sensory and perceptive function, when compared to the students with good academic performance in the same grade; the students from 4th grade, both groups, did not show changes on fine motor, sensory and perceptive function; and only the students of GII showed dysgraphia. Conclusions: the results presented in this study suggest that the qualitative aspects of fine motor, sensory and perceptive skills reflect the integrity and maturity of central nervous system and can probably play an important role in early diagnosis of development disorders and consequently prevent academic disorders such as handwriting performance.

Functional capacity and assistance from the caregiver during daily activities in Brazilian children with cerebral palsy

Background: Cerebral Palsy (CP) presents changes in posture and movement as a core characteristic, which requires multiprofessional clinical treatments during childrens habilitation or rehabilitation. Besides clinical treatment, it is fundamental that professionals use evaluation systems to quantify the difficulties presented to the individual and their families in their daily lives. We aimed to investigate the functional capacity of individuals with CP and the amount of assistance required by the caregiver in day-to-day activities. Methods. Twenty patients with CP, six-year-old on average, were evaluated. The Pediatric Evaluation Inventory of Incapacities was used (PEDI - Pediatric Evaluation Disability Inventory), a system adapted for Brazil that evaluates child's dysfunction in three 3 dimensions: self-care, mobility and social function. To compare the three areas, repeated measures analysis of variance (ANOVA) were used. Results: We found the following results regarding the functional capacity of children: self-care, 27.4%, ±17.5; mobility, 25.8%, ±33.3 and social function, 36.3%, ±27.7. The results of the demand of aid from the caregiver according to each dimension were: self-care, 9.7%, ±19.9; mobility, 14.1%, ± 20.9 and social function, 19.8%, ±26.1. Conclusion: We indicated that there was no difference between the performance of the subjects in areas of self-care, mobility and social function considering the functional skills and assistance required by the caregiver. © 2013 Monteiro et al; licensee BioMed Central Ltd.

Comparison of the caries-preventive effect of a glass ionomer sealant and fluoride varnish on newly erupted first permanent molars of children with and without dental caries experience

Purpose: This longitudinal clinic study evaluated the effect of a glass ionomer sealant (GIS) and a fluoride varnish (FV) in the prevention of dental decay on newly erupted permanent molars of children with and without caries experience. Materials and methods: Eighty children, aged 6-8 years, with all four newly erupted first permanent molars, were divided into two groups. Group 1 consisted of 53 children without caries experience and group 2 consisted of 27 children with dental caries experience. Permanent molars of the right side were sealed with GIS and the fluoride varnish was applied on the other two permanent first molars. Evaluation of GIS retention and the effectiveness of both materials in the prevention of dental caries were performed after 6, 12 and 18 months. Results: After 18 months, of the 299 teeth, 271 (91%) showed no caries lesions and 28 presented caries lesions (9%). Teeth sealed with GIS had more carious lesions (15) than teeth with fluoride varnish (13). Most of the teeth (70%) that presented carious lesions were in group 2. Of the 138 sealed teeth, only one showed GIS to be totally present, 95 were partially present and 42 teeth were absent. Conclusion: The caries-preventive effect was very similar between both treatments. The presence of dental caries prevailed in the children with caries experience. © 2013 Informa Healthcare.