Effects of shared medical appointments compared to individual appointments in children with atopic dermatitis: A pragmatic randomized controlled trial.

BACKGROUND: Atopic dermatitis (AD) needs intensive treatment and has a negative impact on quality of life. Shared medical appointments (SMAs) showed to be effective in clinical outcomes of chronic diseases, but little is known about the effects on children and families. OBJECTIVE: To evaluate the effects of SMAs compared to individual appointments (IA) for children with AD and their parents on coping and clinical outcomes. METHODS: In a pragmatic randomized controlled trial, new patients in UMC Utrecht with AD, younger than 18 years, and their parents were assigned to the SMA group or the IA group using a covariate adaptive randomization method, controlled for age. Before the intervention, 2 months (primary time-point) and 6 months thereafter, we assessed parental emotional coping (primary outcome), quality of life, anxiety about corticosteroids and patient disease activity. Patients, parents and healthcare professionals could not be blinded to group assignment. RESULTS: Of 140 patients, enrolled in the trial, 69 patients were assigned to the SMA and 71 to the IA intervention of whom 114 completed the intervention (SMA: 49; IA: 65). After 2 months, there were no differences between SMAs and IAs in effects on emotional coping: b 0.66, 95% CI -0.7 to 2.03; P = 0.33 (mean difference: 0.30; 95% CI -1.56 to 2.16; N SMA: 11; IA: 24), quality of life, anxiety about corticosteroids and disease activity. From the initial appointment to long-term follow-up, both groups showed substantial improvements, but not significant in disease activity and significant reduction in anxiety about corticosteroids. This study is limited by a low response rate; therefore, linear mixed models and dropout analyses were performed. No serious adverse events were reported. CONCLUSION AND CLINICAL RELEVANCE: For children with AD and their parents, there were no additional benefits of GMAs in parental emotional coping, anxiety about corticosteroids, quality of life and disease activity. TRIAL REGISTRATION: www.ISRCTN.org, ISRCTN08506572.

Explaining the variable penetrance of CNVs: Parental intelligence modulates expression of intellectual impairment caused by the 22q11.2 deletion.

The role of rare genetic variants, in particular copy number variants (CNVs), in the etiology of neurodevelopmental disorders is becoming increasingly clear. While the list of these disorder-related CNVs continues to lengthen, it has also become clear that in nearly all genetic variants the proportion of carriers who express the associated phenotype is far from 100%. To understand this variable penetrance of CNVs it is important to realize that even the largest CNVs represent only a tiny fraction of the entire genome. Therefore, part of the mechanism underlying the variable penetrance of CNVs is likely the modulatory impact of the rest of the genome. In the present study we used the 22q11DS as a model to examine whether the observed penetrance of intellectual impairment-one of the main phenotypes associated with 22q11DS-is modulated by the intellectual level of their parents, for which we used the parents' highest level of education as a proxy. Our results, based on data observed in 171 children with 22q11DS in the age range of 5-15 years, showed a significant association between estimated parental cognitive level and intelligence in offspring (full scale, verbal and performance IQ), with the largest effect size for verbal IQ. These results suggest that possible mechanisms involved in the variable penetrance observed in CNVs include the impact of genetic background and/or environmental influences. © 2016 Wiley Periodicals, Inc.

Behavioral phenotype in children with 22q11DS: agreement between parents and teachers.

Patients with the 22q11-deletion syndrome (22q11DS) are at an increased risk of developing schizophrenia. Besides the effects of genetic variation, environmental factors could also be important in modifying the risk of schizophrenia in 22q11DS patients. In particular, previous studies have shown the importance of stress as a precipitating factor of psychosis. An incongruence between the perceived and actual severity of behavioral and cognitive domains could lead caregivers, and even the children themselves, to make demands that are insufficiently adapted to the child's abilities, causing stress and anxiety. Here, we investigate whether such diagnostic discrepancies are indeed present by comparing parent and teacher reports on behavioral concerns in children with 22q11DS. Behavioral questionnaires (CBCL and TRF) were prepared for both parents and teachers of 146 children with 22q11DS. We found that in line with previous reports, internalizing behavior was more frequently reported than externalizing behavior. While the behavioral profiles reported by parents and teachers were remarkably similar, the teachers' ratings were significantly lower (Total problem score p = .002). Age and IQ were not significantly associated with the severity of reported concerns. Our results indicate that indeed a disparity often exists between parents' and teachers' perceptions of the severity of a child's behavioral deficits. This may result in (substantially) different demands and expectations being placed on the child from the two fronts. We speculate that the stress resulting from this lack of cohesion between parents and teachers could precipitate, at least in some 22q11DS children, the emergence of psychosis.

Rape-related symptoms in adolescents: short- and long-term outcome after cognitive behavior group therapy.

BACKGROUND: Efficacy studies on treatment in adolescent victims of single rape are lacking, even though sexual victimization is most likely to occur during adolescence and despite the fact that adolescents are at risk to develop subsequent posttraumatic stress disorder. AIM: The aim of this prospective observational study was to evaluate the short- and long-term outcomes of a nine-session cognitive behavior group therapy (STEPS), including a parallel six-session parents' group on rape-related symptomatology in female adolescents (13-18 years). STEPS includes psychoeducation, exposure in sensu as well as in vivo, cognitive restructuring, and relapse prevention. METHODS: Fifty-five female adolescents with mental health problems due to single rape, but without prior sexual trauma, received STEPS while their parents participated in a support group. Subjects were assessed on posttraumatic stress (PTS) and comorbid symptoms using self-report questionnaires prior to and directly after treatment, and at 6 and 12 months follow-up. RESULTS: Repeated measures analysis showed a significant and large decrease in symptoms of PTS, anxiety, depression, anger, dissociation, sexual concerns, and behavior problems directly after treatment, which maintained at 12 months follow-up. Time since trauma did not influence the results. Dropout during STEPS was 1.8%. CONCLUSIONS: The results potentially suggest that the positive treatment outcomes at short- and long-term may be caused by STEPS. The encouraging findings need confirmation in future controlled studies on the effectiveness of STEPS because it may be possible that the treatment works especially well for more chronic symptoms, while the less chronic part of the sample showed considerable improvement on its own.

Impaired cognitive functioning in patients with tyrosinemia type I receiving nitisinone.

OBJECTIVE: To examine cognitive functioning in patients with tyrosinemia type I treated with nitisinone and a protein-restricted diet. STUDY DESIGN: We performed a cross-sectional study to establish cognitive functioning in children with tyrosinemia type I compared with their unaffected siblings. Intelligence was measured using age-appropriate Wechsler Scales. To assess cognitive development over time, we retrieved sequential IQ scores in a single-center subset of patients. We also evaluated whether plasma phenylalanine and tyrosine levels during treatment was correlated with cognitive development. RESULTS: Average total IQ score in 10 patients with tyrosinemia type I receiving nitisinone was significantly lower compared with their unaffected siblings (71 ± 13 vs 91 ± 13; P = .008). Both verbal and performance IQ subscores differed (77 ± 14 vs 95 ± 11; P < .05 and 70 ± 11 vs 87 ± 15; P < .05, respectively). Repeated IQ measurements in a single-center subset of 5 patients revealed a decline in average IQ score over time, from 96 ± 15 to 69 ± 11 (P < .001). No significant association was found between IQ score and either plasma tyrosine or phenylalanine concentration. CONCLUSION: Patients with tyrosinemia type I treated with nitisinone are at risk for impaired cognitive function despite a protein-restricted diet.

Cognitive and behavioral trajectories in 22q11DS from childhood into adolescence: a prospective 6-year follow-up study.

Patients with 22q11DS are at risk of behavioral problems and cognitive impairment. Recent studies suggest a possible intellectual decline in 22q11DS children. To date it is unknown if cognitive development is related to the behavioral problems in 22q11DS. We studied 53 children with 22q11DS who underwent cognitive and behavioral assessments at 9.5 years (T1) and 15.3 years (T2). In about one third, IQ data obtained at 7.5 years (T0) were also available. Results showed that internalizing behaviors intensified while externalizing behaviors decreased. Simultaneously, in about a third a significant decline in IQ was found, which, surprisingly, was unrelated to the behavioral changes. It can be concluded that children with 22q11DS follow a unique developmental trajectory. Cognitive deterioration is severe in some but does not appear to predict behavioral problems in early adolescence.

Psychological intervention for adolescents with juvenile idiopathic arthritis: for whom and when?

OBJECTIVE: To study which adolescents with juvenile idiopathic arthritis (JIA) benefit from psychological intervention, and what is the best moment for it. METHODS: In 3 months, 28 adolescents with JIA and 14 healthy adolescents as a control group received psychological intervention with the Self-confrontation Method (SCM), which combines the personal narrative with its affective structure. The adolescents with JIA were split into groups with low health-related quality of life (HRQOL) and high HRQOL. The Child Health Questionnaire, Checklist Individual Strength, and Childhood Health Assessment Questionnaire were used to measure fatigue and physical and psychosocial functioning at baseline, and at 3 months and 9 months after baseline. RESULTS: Adolescents with JIA and low HRQOL at baseline reported less fatigue and better HRQOL after psychological intervention. These changes could not be explained by changes in disease activity. Low HRQOL at baseline was associated with a more recent onset of JIA, higher levels of pain, more severe physical disability, and higher levels of fatigue. CONCLUSION: Two-thirds of adolescents with JIA function well before and after psychological intervention. One-third of adolescents with JIA reporting low HRQOL at baseline benefit from guided self-reflections and should be the focus of psychological intervention. The most effective moment for this psychological intervention is when the adolescent reports difficulties in HRQOL.

Health and identity: Self-positioning in adolescent chronic fatigue syndrome and juvenile idiopathic arthritis.

The aim of this study is to gain more insight into basic aspects of identity, in relation to adolescent chronic fatigue syndrome (CFS) and juvenile idiopathic arthritis (JIA). In dialogical self theory, identity is regarded as incorporating multiple self-positions, such as 'I as tired', 'I as pessimistic', or 'I as decisive'. Physical and psychosocial impairment might alter the organization of these self-positions. The Personal Position Repertoire procedure, a quantitative method to analyse the prominence of self-positions, the Child Health Questionnaire, assessing health-related functioning, and the Checklist Individual Strength, measuring fatigue, were completed by 42 adolescents with CFS, 37 adolescents with JIA and 23 healthy teenagers. Adolescents with JIA report impaired physical functioning and general health. However, they position themselves very similar to healthy teenagers - i.e. as strong and healthy. While this self-positioning approach might be adequate and sustainable in adolescence, it could prove too strenuous to maintain throughout adult life. Adolescents with CFS, besides indicating severe physical difficulties, also report more psychosocial problems. They position themselves as significantly less strong and more unwell. With this emphasis on positions relating to their illness, there seems to be little room left for stronger positions. It is regarded of clinical importance to address these issues in this crucial developmental period.

Salivary cortisol and dehydroepiandrosterone sulfate in adolescent rape victims with post traumatic stress disorder.

BACKGROUND: In chronic sexual abuse victims with post traumatic stress disorder (PTSD), the hypothalamic pituitary adrenal (HPA) axis can be dysregulated. In single rape victims, PTSD symptoms are hypothesized to function as a chronic stressor leading to similar HPA-axis dysregulation. The objective of the current study was to assess HPA-axis functioning in female adolescents with rape-related PTSD, but no prior sexual trauma, in comparison to non-victimized controls. METHOD: Salivary cortisol and dehydroepiandrosterone sulfate (DHEAS) were measured in 52 female adolescent rape victims with PTSD and 37 healthy adolescents at 0, 15, 30, 45 and 60 min after awakening, both under basal conditions and after 0.5 mg dexamethasone administration. RESULTS: Compared to age-matched controls, adolescent rape victims with PTSD showed significantly reduced cortisol and DHEAS levels. No group differences for the effect of dexamethasone suppression were found. Both the event of rape and PTSD diagnosis, and not factors such as sleep duration, smoking, education or oral contraceptives, accounted for the neuroendocrine differences between rape victims and controls. CONCLUSIONS: The results show evidence for a dysregulated HPA-axis in female adolescent victims of single sexual trauma with PTSD. The finding of hypocortisolism is consistent with endocrine dysfunctioning in chronic sexual abuse victims and may have clinical implications with regard to treatment possibilities.

Behavior in preschool children with the 22q11.2 deletion syndrome.

Children with the 22q11.2 deletion syndrome (22q11DS) are at an increased risk of psychiatric problems from pre-adolescence; little is known, however, about behavioral problems at a preschool age and the relationship between speech and behavior in this group. Parents of 90 children (aged 1.42-5.99 years) with 22q11DS filled out the Child Behavior Checklist, documenting behaviors including speech problems. Their profiles were compared with those of a comparison group consisting of 33 children with nonsyndromic orofacial clefts without 22q11DS, since both children with 22q11DS and children with clefts are expected to have speech problems. In the 22q11DS group, data on intelligence was acquired by means of formal tests. Parents of children with 22q11DS reported significantly higher mean scores on withdrawn behavior, affective problems and pervasive developmental problems compared to children with nonsyndromic clefts. Approximately 30% of children with 22q11DS had a score above the 97th percentile on at least one of the behavior subscales, indicating psychopathology. In children with 22q11DS, the reported behavioral problems were not associated with speech problems. Behavioral problems were found in 30% of young children with 22q11DS and were unlikely to be caused by speech problems. Within the 22q11DS group, behavioral problems were not related to the degree of cognitive impairment. This shows that many children with 22q11DS, known to be at an increased risk of psychiatric problems from pre-adolescence, already show behavioral problems before the age of 6 years.

Cognitive development in children with 22q11.2 deletion syndrome.

BACKGROUND: People with 22q11.2 deletion syndrome (velo-cardio-facial syndrome) have a 30-fold risk of developing schizophrenia. In the general population the schizophrenia phenotype includes a cognitive deficit and a decline in academic performance preceding the first episode of psychosis in a subgroup of patients. Findings of cross-sectional studies suggest that cognitive abilities may decline over time in some children with 22q11.2 deletion syndrome. If confirmed longitudinally, this could indicate that one or more genes within 22q11.2 are involved in cognitive decline. AIMS: To assess longitudinally the change in IQ scores in children with 22q11.2 deletion syndrome. METHOD: Sixty-nine children with the syndrome were cognitively assessed two or three times at set ages 5.5 years, 7.5 years and 9.5 years. RESULTS: A mean significant decline of 9.7 Full Scale IQ points was found between ages 5.5 years and 9.5 years. In addition to the overall relative decline that occurred when results were scored according to age-specific IQ norms, in 10 out of a group of 29 children an absolute decrease in cognitive raw scores was found between ages 7.5 years and 9.5 years. The decline was not associated with a change in behavioural measures. CONCLUSIONS: The finding of cognitive decline can be only partly explained as the result of 'growing into deficit'; about a third of 29 children showed an absolute loss of cognitive faculties. The results underline the importance of early psychiatric screening in this population and indicate that further study of the genes at the 22q11.2 locus may be relevant to understanding the genetic basis of early cognitive deterioration.

Intelligence and visual motor integration in 5-year-old children with 22q11-deletion syndrome.

The purpose of this study was to explore the relationship between intelligence and visual motor integration skills in 5-year-old children with 22q11-deletion syndrome (22q11DS) (N = 65, 43 females, 22 males; mean age 5.6 years (SD 0.2), range 5.23-5.99 years). Sufficient VMI skills seem a prerequisite for IQ testing. Since problems related to these skills are reported in children with 22q11DS, weak VMI skills may contribute to the lower than average IQ scores commonly reported. To investigate if the correlation of VMI and IQ score was mainly influenced by problems with visual perception skills (VP), motor coordination skills (MC) or difficulties with the integration of both skills (VMI), a subgroup (n = 28) was also administered the Beery VMI supplemental developmental tests. Due to the narrow age range of this study, we were also able to provide an insight into the neurocognitive phenotype of 5-year olds with 22q11DS and the influence of gender, heart disease and origin of deletion on this phenotype. Results show a mean full scale IQ (FSIQ) = 73.0 (SD 10.4) and mean VMI = 86.2 (SD 8.4). A significant correlation between FSIQ and VMI was found (r = .45, p = .000), with most variation (26%) explained in the performance IQ score ((PIQ), r = .51, p = .000). VP correlated significantly with FSIQ (r = .44, p = .01) and PIQ (r = .49, p = .004). MC was not significantly correlated with IQ (FSIQ, r = .21, p = .15; PIQ, r = .28, p = .07), suggesting that problems with motor coordination do not influence results on IQ-tests in a significant way at this age. Girls scored significantly higher on FSIQ and PIQ than boys; cardiac anomalies were not predictive of FSIQ or VMI scores. The results of this study suggest a characteristic neurocognitive phenotype for 5-year olds with 22q11DS. Deficiencies in visual perception and/or processing are negatively correlated with IQ scores, whereas deficiencies in motor skills do not have a relevant negative impact at this age. These findings provide further insight into 22q11DS specific neurocognitive deficiencies.

High prevalence of methotrexate intolerance in juvenile idiopathic arthritis: development and validation of a methotrexate intolerance severity score.

OBJECTIVE: To design and validate a new questionnaire for identifying patients with methotrexate (MTX) intolerance, and to determine the prevalence of MTX intolerance in patients with juvenile idiopathic arthritis (JIA) using this questionnaire. METHODS: The MTX Intolerance Severity Score (MISS) questionnaire was constructed, consisting of 5 domains: stomach ache, nausea, vomiting, sore mouth, and behavioral symptoms. The domains each consisted of 3 questions pertaining to the presence of a symptom upon, prior to (anticipatory), and when thinking of (associative) MTX intake. The MISS questionnaire was validated in 86 patients by determining its discriminative power between patients with and those without MTX intolerance, identified as such by a gold standard (physician's opinion). Using the MISS questionnaire, the prevalence of MTX intolerance was determined in 297 JIA patients. RESULTS: The MISS questionnaire discriminated well between MTX-intolerant and MTX-tolerant patients. A cutoff score of 6 yielded the best sensitivity (88%) and specificity (80%). MTX intolerance was found in 150 (50.5%) of 297 patients. Of 220 patients receiving oral MTX, 98 (44.5%) experienced MTX intolerance, whereas 67.5% of 77 patients receiving parenteral MTX experienced intolerance to the drug (P = 0.001). CONCLUSION: Our findings indicate that the MISS questionnaire is a highly sensitive and specific tool for the diagnosis of MTX intolerance, and that there is a high prevalence of MTX intolerance among JIA patients. The prevalence of intolerance in patients receiving parenteral MTX exceeds that in patients receiving oral MTX. The frequent occurrence of anticipatory and associative symptoms suggests that classic conditioning plays an important role in MTX intolerance.

Effects of an educational video film in fatigued children and adolescents: a randomised controlled trial.

BACKGROUND: In many cases standard management for chronic fatigue syndrome (CFS) in children and adolescents is ineffective. OBJECTIVE: To evaluate the efficacy of a video film intervention in preventing the development of persistent fatigue and significant school absence in fatigued children and adolescents. DESIGN: Randomised controlled trial. PARTICIPANTS: 91 patients with fatigue; 50 were randomly assigned to receive the intervention (video film plus usual care) and 41 to usual care only. INTERVENTION: A video film on CFS and coping behaviour. MAIN OUTCOME MEASURES: Self-reported fatigue severity, physical activity, motivation, concentration and school absence. RESULTS: 79 patients had complete data at 12 months (42 in the video film and 37 in the usual care group). Mean fatigue severity and school absenteeism scores did not differ significantly, but in the intervention group the score for reduced motivation was higher (difference 2.9 (CI 0.1 to 5.7), p=0.038). 18% more patients in the intervention compared to the usual care group also had persistent fatigue with significant school absence. The odds of developing persistent fatigue and of missing >50% of school classes was 3.3 times higher in the intervention than in the usual care group (OR 3.3 (CI 1.0 to 11.3), p=0.046). CONCLUSION: This particular video film intervention plus usual care in children and adolescents with unexplained fatigue did not prevent an unfavourable outcome and possibly had an adverse effect in that it reduced motivation and increased the incidence of persistent fatigue with significant school absence. The use of this particular film is not recommended.

Self-investigation in adolescent chronic fatigue syndrome: narrative changes and health improvement.

OBJECTIVE: A small-scale intervention study into narrative self-investigation in adolescent chronic fatigue syndrome (CFS). METHOD: The self-confrontation method (SCM) is an instrument to assess and change personal life stories. Forty-two adolescents diagnosed with CFS were included and randomly assigned to either 6 or 12 sessions with the SCM. Twenty-five healthy adolescents were assigned to 6 sessions. Outcome was measured directly after the self-investigation procedure at 4 months. Follow-up measurements were made 10 months later. The Checklist Individual Strength and the Child Health Questionnaire were used to measure changes in fatigue, physical and psychosocial functioning. RESULTS: Self-investigation resulted in significant changes in participants' narratives. Moreover, after self-investigation there was a significant improvement in fatigue, physical and psychosocial functioning for the adolescents with CFS. The patients who completed 12 sessions improved most. At follow-up, the positive effects were maintained. CONCLUSION: Self-investigation enables a move beyond the symptoms of CFS in an individualized, patient centered way. Narrative transformation seems to contribute to improved physical and psychosocial outcome in adolescent CFS. PRACTICE IMPLICATIONS: The SCM allows adolescents to discover (for themselves) factors that might cause or perpetuate their fatigue. The results suggest that self-investigation is a useful instrument in the management of adolescent CFS.

Design of the Quality of Life in Motion (QLIM) study: a randomized controlled trial to evaluate the effectiveness and cost-effectiveness of a combined physical exercise and psychosocial training program to improve physical fitness in children with cancer.

BACKGROUND: Childhood cancer and its treatment have considerable impact on a child's physical and mental wellbeing. Especially long-term administration of chemotherapy and/or radiotherapy impairs physical fitness both during and after therapy, when children often present with muscle weakness and/or low cardiorespiratory fitness. Physical exercise can improve these two elements of physical fitness, but the positive effects of physical exercise might be further increased when a child's wellbeing is simultaneously enhanced by psychosocial training. Feeling better may increase the willingness and motivation to engage in sports activities. Therefore, this multi-centre study evaluates the short and long-term changes in physical fitness of a child with a childhood malignancy, using a combined physical exercise and psychosocial intervention program, implemented during or shortly after treatment. Also examined is whether positive effects on physical fitness reduce inactivity-related adverse health problems, improve quality of life, and are cost-effective. METHODS: This multi-centre randomized controlled trial compares a combined physical and psychosocial intervention program for children with cancer, with care as usual (controls). Children with cancer (aged 8-18 years) treated with chemotherapy and/or radiotherapy, and who are no longer than 1 year post-treatment, are eligible for participation. A total of 100 children are being recruited from the paediatric oncology/haematology departments of three Dutch university medical centres. Patients are stratified according to pubertal stage (girls: age ≤10 or >10 years; boys: ≤11 or >11 years), type of malignancy (haematological or solid tumour), and moment of inclusion into the study (during or after treatment), and are randomly assigned to the intervention or control group. DISCUSSION: Childhood cancer patients undergoing long-term cancer therapy may benefit from a combined physical exercise and psychosocial intervention program since it may maintain or enhance their physical fitness and increase their quality of life. However, the feasibility, patient need, and effectiveness of such a program should be established before the program can be implemented as part of standard care. TRIAL REGISTRATION NUMBER: NTR1531 (The Netherlands National Trial Register).

Parental anxiety before and after food challenges in children with suspected peanut and hazelnut allergy.

As ingestion of peanut and hazelnut by allergic children is potentially life threatening, parents of these children need to be vigilant about their child's dietary intake. This may cause high levels of anxiety. To assess parental anxiety about food-allergic reaction in their child (state anxiety) and their personal disposition to anxiety (trait anxiety). Parental anxiety was investigated again after food challenges. Fifty-seven children (3-16 yr, mean age 7.2) with suspected peanut or hazelnut allergy (mean specific IgE 20.9) were evaluated by double-blind, placebo-controlled food challenge (DBPCFC). Thirty-two children (56%) developed an allergic reaction. All parents completed the Spielberger State-Trait Anxiety Inventory (STAI) prior to DBPCFC and 2 wk, 3 months and 1 yr thereafter. The mean anxiety scores on these moments were compared with each other and with general Dutch norms. The STAI was also investigated in a group that refused DBPCFC. Prior to DBPCFC, parents had high levels of state anxiety in contrast to a lower trait anxiety compared to the norm group. After DBPCFC, the state anxiety was significantly lower, regardless of a positive or negative outcome (p

Long-term psychosocial functioning after Ilizarov limb lengthening during childhood.

BACKGROUND AND PURPOSE: Few studies have been concerned with the patient's perception of the outcome of limb lengthening. We describe the psychological and social functioning after at least 2 years of follow-up in patients who had had a leg length discrepancy and who had undergone an Ilizarov limb lengthening procedure. PATIENTS AND METHODS: Self-esteem and perceived competence were measured in 37 patients (aged 17-30 years) both preoperatively and at a mean follow-up of 7 (2-14) years. At follow-up, health-related quality of life, functioning at school, daily activities, and treatment-related experiences were measured, and also retrospectively for the preoperative period. RESULTS: Preoperative and follow-up scores for self-esteem were similar. Overall perceived competence scores at follow-up were comparable to that of a healthy normal population. Patients' perceived athletic competence was lower and their perceived level of behavioral conduct was higher. At follow-up, patients had more positive appraisal of their physical appearance. Most health-related quality of life scores were not significantly different to those of the healthy normal population, apart from a reduced gross motor function, less vitality, and more pain. Patients with a remaining leg length inequality (LLI) of more than 2 cm had lower quality of life scores for gross motor function, sleep, pain, vitality, and depressive feelings. INTERPRETATION: At an average of 7 years after an Ilizarov limb lengthening procedure, patients still have physical restraints, but they appear to have normal psychosocial functioning, self-esteem, and perceived competence. These patients have quality of life scores comparable to those of norm groups, apart from a reduced gross motor function, less vitality and more pain. Residual LLI of more than 2 cm remains important even after long-term follow-up; these patients report lower quality of life.

Risk factors for persistent fatigue with significant school absence in children and adolescents.

OBJECTIVE: To assess children and adolescents with severe fatigue who are referred to pediatricians and to examine whether factors can be identified at their first visit that predict worse outcomes at 1 year. METHODS: Ninety-one patients, aged 8 to 18 years completed questionnaires about sleep, somatic symptoms, physical activity, and fatigue. They were reassessed 12 months later. Measurements at baseline and outcome were analyzed by using univariable logistic regression with persistent, severe fatigue (yes/no) and persistent school absence (yes/no) as dependent variables and baseline scores as independent variables. RESULTS: After 12 months, 50.6% of the children and adolescents showed improvement; 29.1% had persistent fatigue, and 20.3% had persistent fatigue with significant school absence. Factors associated with the poorest outcome were sleep problems (odds ratio [OR]: 1.4 [95% confidence interval (CI): 1.1-1.8]), initial fatigue score (OR: 1.1 [95% CI: 1.0-1.2]), somatic complaints such as hot and cold spells (OR: 1.9 [95% CI: 1.2-3.0]), blurred vision (OR: 2.1 [95% CI: 1.1-4.0]), pain in arms and legs (OR: 2.0 [95% CI: 1.0-3.2]), back pain (OR: 1.8 [95% CI: 1.0-3.2]), constipation (OR: 1.7 [95% CI: 1.0-2.7]), and memory deficits (OR: 1.8 [95% CI: 1.0-3.2]). Resolved fatigue was associated with male gender (OR: 5.0 [95% CI: 1.6-15.5]) and a physically active lifestyle (OR: 1.3 [95% CI: 1.1-1.5]). CONCLUSIONS: Assessment of predictive factors at the first visit enables the pediatrician to identify those patients with severe fatigue who are at risk of a poor outcome. Female gender, poor sleep quality, physically inactive lifestyle, and specific somatic complaints were important predictive factors.

Behavior and development in children and age at the time of first anesthetic exposure.

BACKGROUND: Several experimental studies have suggested that early exposure to anesthetic agents, i.e., before completion of synaptogenesis, can result in widespread apoptotic neuronal degeneration and late cognitive impairment, but human data are lacking. The authors performed a retrospective pilot study to test the feasibility and calculate sample sizes for a larger epidemiologic study of disturbed neurobehavioral development as a function of age at the time of first anesthetic exposure. Pediatric urological procedures were selected because the timing of surgery depends mainly on the age at which a diagnosis is made. METHODS: Neurobehavioral development was assessed using the validated 120-item parental Child Behavior CheckList/4-18 in 314 children who were operated for pediatric urological procedures between the ages of 0 and 6 yr. RESULTS: Of 243 questionnaires returned, the total problem score was clinically deviant in 41 (23%) of children aged less than 24 months at the time of first surgery and 13 (20%) aged greater than 24 months. Crude and adjusted odds ratios for a clinically deviant Child Behavior CheckList/4-18 score increased with younger age at the time of surgery, but the confidence intervals were very wide. Adjusted odds ratio was 1.38 (0.59-3.22) when operated at age less than 6 months, 1.19 (0.45-3.18) when operated between 6 and 12 months of age, and 1.20 (0.45-3.20) when operated between 12 and 24 months (using operated at greater than 24 months of age as reference category). A properly powered cohort study would require at least 2,268 children. CONCLUSIONS: Children undergoing urologic surgery at age less than 24 months showed more behavioral disturbances than children in whom surgery was performed after age 2 yr, although the results were not statistically significant. To confirm or refute an effect of anesthesia on cognitive development, at least 2,268 children need to be studied. With retrospective study designs, residual confounding remains an issue that can only be solved in prospective randomized studies.