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.

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.

Efficacy, safety and tolerability of terbinafine for Tinea capitis in children: Brazilian multicentric study with daily oral tablets for 1, 2 and 4 weeks

Background: Tinea capitis is a common skin disease seen predominantly in children. The standard therapies for this disease are griseofulvin and ketoconazole. Nevertheless, these drugs have drawbacks in that they are only fungistatic and require treatment for at least 6 weeks. Previous studies with oral terbinafine for the treatment of Tinea capitis have shown that this agent is effective when given for 4 weeks, comparable to an 8-week regimen with griseofulvin. To date there is no data on the use of oral terbinafine in Brazilian children. Objectives: To assess the efficacy, safety and tolerability of oral terbinafine in short-term treatments (1-, 2- and 4-week treatment) of Tinea capitis in children. Patients and methods: One hundred and thirty-two children aged 1-14 years were enrolled in this study, but only 107 were considered for the final efficacy analysis. Diagnosis included clinical assessment and examination by Wood's light. Confirmation was obtained by direct microscopy and culture for fungus. Terbinafine dosage (125 or 250 mg/day) was adjusted according to patient weight. Efficacy was evaluated both by clinical and mycological assessment. Safety and tolerability variables included data on adverse reaction and clinical laboratory evaluations. Results: Mycological evaluation in the follow-up visit at week 12 showed negative direct microscopy and culture results in 48.6, 60.5 and 69.7% patients in groups 1-, 2- and 4-week, respectively (n.s.). At week 12, 84.8% patients in group 4-week achieved clinical cure with a significant difference compared to groups 1- and 2-week, 54.3 and 60.5%, respectively (P < 0.01). Adverse reactions were present in 4.8, 6.8 and 10.9% of patients in groups 1-, 2- and 4-week, respectively. Terbinafine was not associated with clinically relevant increases in liver function tests. Conclusions: Terbinafine is an effective, well tolerated and safe antifungal agent for the treatment of Tinea capitis m children. The shorter duration of treatment resulted in lower cure rates. However, it is important to note that depending on the severity of the disease, a 1-week-only treatment can also be effective in this indication.

Postural control in children: Coupling to dynamic somatosensory information

The purpose of this investigation was to determine whether the coupling between dynamic somatosensory information and body sway is similar in children and adults. Thirty children (4-, 6-, and 8-year-olds) and 10 adults stood upright, with feet parallel, and lightly contacting the fingertip to a rigid metal plate that moved rhythmically at 0.2, 0.5, and 0.8 Hz. Light touch to the moving contact surface induced postural sway in all participants. The somatosensory stimulus produced a broadband frequency response in children, while the adult response was primarily at the driving frequency. Gain, as a function of frequency, was qualitatively the same in children and adults. Phase decreased less in 4-year-olds than other age groups, suggesting a weaker coupling to position information in the sensory stimulus. Postural sway variability was larger in children than adults. These findings suggest that, even as young as age 6, children show well-developed coupling to the sensory stimulus. However, unlike adults, this coupling is not well focused at the frequency specified by the somatosensory signal. Children may be unable to uncouple from sensory information that is less relevant to the task, resulting in a broadband response in their frequency spectrum. Moreover, higher sway variability may not result from the sensory feedback process, but rather from the children's underdeveloped ability to estimate an internal model of body orientation.

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.

The mandibular lingula's position in children as a reference to inferior alveolar nerve block

Purpose: The objective of this study was to evaluate the position of the mandibular lingula (ML) to provide data for inferior alveolar nerve block techniques in children. Methods: One hundred fifty-four panoramic radiographs of 7- to 10-year-old boys and girls were analyzed. Measurements were taken from the ML to the occlusal plane, and the percentile distances of the ML to ramal borders were determined. Results: The distance between the ML and the occlusal plane showed a gradual increase, but only in the male group was it statistically significant. MLs ratio position on the ramus remained constant in all analyzed groups. In the 7-year-old group, the ML was observed above the occlusal plane in 70% of girls and 55% of boys. That percentage reached 85% of all children by age 10. Conclusions: The mandibular lingula's ratio position remained constant. Inferior alveolar anesthesia should be administered at least 6 mm above the occlusal plane in 7- to 8-year-old children, while 10 mm could be indicated for 9- to 10-year-old children. The mandibular lingula should be considered a reliable reference for further studies of inferior alveolar nerve block techniques.

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.

Prevalence of enamel white spots and risk factors in children up to 36 months old

The aim of this study was to determine the prevalence of enamel white spots and the quality of oral hygiene in children up to 36 months old, in municipalities with different fluoride levels in the water supply, analyzing the contribution of several variables. After approval of the Ethics Committee, the parents signed an informed consent form and were interviewed about their educational level, economic classification of the family, nursing habits, use of toothpaste, access to dental service and other information. The children were clinically examined using the same codes and criteria established by the WHO (World Health Organization) and ADA (American Dental Association). The data were processed and analyzed with the Epi-info software program, version 3.2, and Microsoft Excel. Fisher's exact test (p<0.05) was applied to assess the association among the variables. The enamel white spot prevalence was 30.8% and the age group, duration of the bedtime milk feeding habit, age of initial practice of oral hygiene and presence of caries lesions with cavitation were considered statistically significant with regard to enamel white spot prevalence (p < 0.05). No association was found between oral hygiene quality and the study variables. © 2009 Sociedade Brasileira de Pesquisa Odontológica.

Caries experience associated to social and preventive factors in children of a pastoral community from Limeira-SP

Aim: To evaluate caries experience and prevalence associated to social and preventive factors in 3-6-year-old children of a Pastoral Community from Limeira, Brazil. Methods: A cross-sectional study was carried out through an epidemiologic research about the oral conditions of 110 children registered at the Children's Pastoral Community from the city of Limeira, SP, Brazil. Intraoral examination was performed by a trained dentist and the parents/caregivers filled out a questionnaire in order to outline the children's profile with respect to gender, parental education and oral health. Results: Differences related to gender were not detected (p= 0.3404). The most frequent periods of breastfeeding were 0 to 2 months (36.36%) and 2 to 6 months (35.45%), corresponding to 71.81% of the cases. The time bottle feeding pointed to two most frequent categories: 1) more than 12 months (35.45%) and 2) between 2 and 6 months (22.63%). Regarding parental education, the majority of the sample has not completed primary school (38.32%). It was observed a larger number of decayed teeth in male children (63.39%). Caries experience was significantly higher in children who were breastfed for only 2 months of life (41.96%). Children that did not use baby bottle or did not use a baby bottle for more than 1 year presented a smaller dmft, corresponding to 29.17% and 28.33%, respectively. Time of use of bottle and pacifier presented a significant association (p<0.05). Conclusions: The implementation of adequate strategies and actions is needed to reinforce oral health conditions in risk groups.

Dynamic exercise versus tag game warm up: The acute effect on agility and vertical jump in children

Although dynamic and stretching exercises have been widely investigated, there is little information about warm up performed by tag games. Thus, the purpose of the present study was to verify the acute effect of dynamic exercises compared to a tag game warm up on agility and vertical jump in children. 25 boys and 24 girls participated in this study and performed the agility and vertical jump tests after warm up based on dynamic exercises or as a tag game lasting 10 min each in two different days randomly. Dynamic exercises warm up consisted in a run lasting 2.5 min followed by 2 series of 8 dynamic exercises lasting 10 seconds each interspersed with 20s of light run to recovery. Tag game warm up was performed by a tag game with two variations lasting 5 min each. The first variation there was a single cather, which aimed to get the other participants by touching hands. In the second part of the game, the rules were the same except that the participant that was caught had to help the catcher forming a team of catchers. Warm up intensity was monitored by OMNI perceived exertion scale. ANOVA 2x2 for repeated measures (Warm up x Sex) demonstrated no significant differences between dynamic exercises and tag game for agility and vertical jump (P>0.05) for boys and girls. Perceived exertion was significantly higher in tag game compared to dynamic exercises on girls (P<0.05). Both warm up models showed similar acute effects on agility and vertical jump in children. © Faculty of Education. University of Alicante.

Molar incisor hypomineralisation: Possible aetiological factors in children from urban and rural areas

Aim: To analyse factors potentially associated with molar incisor hypomineralisation (MIH) development. METHODS: A population-based study was carried out with 903 children aged from 6-12 years old, born and residing in rural and urban areas of the town of Botelhos, State of Minas Gerais, Brazil. Their mothers completed a structured medical history questionnaire, from pregnancy to the child's 3rd year of life. Two examiners evaluated children for MIH according to criteria suggested by the European Academy of Paediatric Dentistry. Descriptive analyses of the data and odds ratios (OR) with 95% test-based confidence intervals (CI) were estimated. Chisquare test was used to evaluate the differences between groups. RESULTS: The prevalence of MIH in children from rural area (RA) was significantly higher than those from the urban area (UA) (24.9% versus 17.8%, p= 0.01). In urban children, neither significant associations with MIH nor medical problems were found. In rural children, however, MIH was significantly more common among those whose mothers had experienced medical problems during pregnancy (OR=2.11; 1.01-4.37 CI 95%; p=0.04), who had throat infections (OR=2.93; 1.47-5.87 CI 95%; p=0.01), who had high fever (OR=1.91; 1.07-3.39 CI 95%; p=0.02), and who had used amoxicillin associated with other antibiotics (OR=1.92; 1.02-3.62 CI 95%; p=0.04) during the first 3 years of life. CONCLUSION: This study suggests a link between MIH and health problems during pregnancy, as well as environmental factors.

In vitro and in vivo inhibition of acetylcholinesterase and carboxylesterase by metals in zebrafish (Danio rerio)

Metals are natural components in ecosystems; however, if these elements are in excess, they can have adverse effects on living organisms. This study analyzes the interference of copper, lead, iron and cadmium in acetylcholinesterase (AChE) and carboxylesterase (CbE) activities in zebrafish. AChE was significantly inhibited in vitro by copper, iron, lead and cadmium at higher concentrations (10 and 20 mmol/L), whereas CbE was inhibited only at a concentration of 20 mmol/L. In vivo, only lead and cadmium were able to cause AChE inhibition at higher concentrations, while iron didn't cause any changes, and copper promoted an increase in AChE activity at a concentration of 0.06 mg/L. CbE activity did not change at any of the times (two and seven days) and concentrations tested, except in the case of copper exposure, which resulted in a decrease in CbE activity. Indeed, iodoacetamide treatment didn't changed AChE neither CbE activities, results which indicate that the metal inhibiting effect is probably not due to its biding to thiol groups close the active site of the enzyme. This outcome reveals that metals are important esterase inhibitors in zebrafish, and should be considered in environmental monitoring studies that use esterase inhibition as exposure biomarkers of organophosphate and carbamate pesticides. © 2012 Elsevier Ltd. All rights reserved.

Motor intervention in children with school learning difficulties

This study sought to evaluate motor development in children aged 6 to 11 years with learning difficulties and school characteristics of delayed motor development, before and after application of a motor intervention program. The sample consisted of 28 children with a mean age of 107.21 ± 16.56 months, who were evaluated by the Motor Development Scale and received motor intervention for 6 months, followed by reassessment. We observed a statistically significant difference between the average of the motor activity ratios in all areas of the evaluation and reevaluation. Also verified in the evaluation were the concentration ratios of children with motor activity greater than or equal to 80 and there was a revaluation increase in this concentration on re-evaluation, the areas with the greatest increase in concentration and significant differences being: Body Schema, Space and temporal Organization. In the overall evaluation of MDS, most children presented the classification of low normal. However, in the reassessment most have evolved into the average normal, only 4 of themremaining in the same classification. Therefore, in this study, children with learning disabilities also showed motor deficits and the intervention applied contributed to an increase in the motor ratios with consequent improvement in motor development. Besides psychopedagogical asistance, it is essential to reassess them and if necessary apply the intervention in the motor development of children with learning difficulties.