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)

The oral blue nevus in children: a case report.

The intraoral blue nevus is a benign, relatively rare lesion that usually occurs in adults and most often in women. The reported case is interesting because the patient was only 11 years old. The lesion, located in the hard palate, was surgically removed. The specimen was sent for histologic examination, resulting in the final diagnosis of common blue nevus.

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.

Treatment of mucus retention phenomena in children by the micro-marsupialization technique: case reports

The purpose of the present study was to emphasize the technique of micro-marsupialization as an alternative for the treatment of mucus retention phenomena. Out of 41 patients, 14 were selected for treatment by the micro-marsupialization technique on the basis of clinical criteria. Patient age ranged from 5-9 years. The technique was performed as follows: the area was disinfected with 0.1% iodine; a topical anesthetic was applied to cover the entire lesion for approximately 3 min; a 4.0 silk suture was passed through the internal part of the lesion along its widest diameter; and a surgical knot was made. Of the original 14 patients treated by the micro-marsupialization technique, 12 presented full regression one week after treatment. Recurrence occurred in two cases. It was possible to conclude that the micro-marsupialization technique is an alternative to be considered, especially in pediatric dentistry.

Use of dental implants in children: A literature review

The aim of this literature review is to discuss the use of dental implants in growing patients and the influence of maxillary and mandibular skeletal and dental growth on the stability of those implants. It is recommended to wait for the completion of dental and skeletal growth, except for severe cases of ectodermal dysplasia.

Behavioral evaluation during dental care in children ages 0 to 3 years

Purpose: Many studies concluded that the behavior of babies complicated dental care because of child immaturity or the difficulty of establishing acceptable communication and comprehension. Methods: The records of 696 babies were randomly selected from the baby clinic of Araçatuba in Brazil. Patient age ranged from 0 to 36 months. They were divided into 6 groups according to age: Group I-0 to 6 months; Group II-7 to 12 months; Group III-13 to 18 months; Group IV-19 to 24 months; Group V-25 to 30 months; Group VI-31 to 36 months. The behavior of the child was evaluated upon entrance in the dental office and during the first 4 clinical appointments with a clinical exam and oral physiotherapy. The baby was classified as collaborator (C) or noncollaborator (NC). Statistical analysis was performed using Pearson's chi-square method (P< .05). Results: The percentage of NC for Groups II, III, IV, and V (66%), was significantly higher than for groups I (30%) and VI (50%). Conclusions: Babies from 0 to 6 months showed a collaborative behavior; babies from 7 to 30 months showed noncollaborative behavior; and babies from 31 to 36 months showed no statistically significant difference between the percentage of C and NC.

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.

Cinedacryocystography in the diagnosis of lacrimal obstruction in children

Purpose: To analyze the cinedacryocystography in children with congenital nasolacrimal obstruction suspicion. Methods: The cinedacryocystographic examination was done in 143 children (58% of girls and 42% of boys) younger than 5 years old, suspected of congenital nasolacrimal obstruction. The exams were done under general anesthesia and the children were probed immediately when obstruction was detected. Results: Epiphora, discharge or both were the most common complaints. Nevertheless 11% children had undergone unsuccessfully probing once, no one had any radiologic evaluation previously. The cinedacryocystographic exam showed nasolacrimal duct obstruction in 65,73%. Permeable lacrimal vies were presented in 34,3% of the children with epiphora. The obstruction was mainly at the Arlt's sinus. Using the cinedacryocystography, it was possible to observe the lacrimal sac enlargement and alterations in the contiguous structures such as hypertrophic turbinates (91,1%), sinusitis (44,6%) and septum deviation (24,1%). Conclusion: Cinedacryocystographic evaluation provides important information about lacrimal system obstruction in children, therefore, it is useful in all children with suspected congenital lacrimal obstruction.

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.

Familial malignant osteopetrosis in children: A case report

The clinical, radiological, pathological and laboratory findings of two brothers with autosomal recessive malignant osteopetrosis are presented. Our findings are similar to characteristics previously reported in the literature about patients with osteopetrosis. The 6-year-old male patient was pale and had petechiae on his arms and legs. He also had macrocephalia, splenomegaly, severe pancytopenia, genu valgus, hypocalcemia, amaurosis, cessation of physical development, generalized bone sclerosis and recurrent infections with a history of multiple incidences of acute otitis media. Generalized bone sclerosis and irregular sclerosis of the maxilla and mandible were seen on radiographs. The oral mucosa was apparently normal but permanent tooth eruption was delayed although there was early loss of deciduous teeth. The recommended treatment was blood transfusion and therapy with antibiotics when necessary; a bone marrow transplant was not possible due to lack of a compatible donor.

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.