A dietary fiber mixture versus lactulose in the treatment of childhood constipation: a double-blind randomized controlled trial.

BACKGROUND: Constipation is a common problem in children. As first-line treatment, increased dietary fiber is often advocated. To our knowledge, however, no large studies evaluating the effect of dietary fibers in childhood constipation have been published. PATIENTS AND METHODS: A randomized, double-blind, prospective controlled study was performed. Patients received either a fiber mixture or lactulose in a yogurt drink. After a baseline period of 1 week, patients were treated for 8 weeks followed by 4 weeks of weaning. Polyethylene glycol 3350 was added if no clinical improvement was observed after 3 weeks. Using a standardized bowel diary, parents recorded defecation frequency during the treatment period. In addition, incontinence frequency, stool consistency, presence of abdominal pain and flatulence, necessity for step-up medication, and dry weight of feces were recorded, as were adverse effects. RESULTS: A total of 147 children were eligible; 12 children wished not to participate. Of the remaining children, 65 were randomized to treatment with fiber mixture and 70 to treatment with lactulose. In all, 97 children completed the study. No difference was found between the groups after the treatment period concerning defecation frequency (P = 0.481) and fecal incontinence frequency (P = 0.084). However, consistency of stools was softer in the lactulose group (P = 0.01). Abdominal pain and flatulence scores were comparable (P = 0.395 and P = 0.739, respectively). The necessity of step-up medication during the treatment period was comparable (P = 0.996), as were taste scores (P = 0.657). No serious adverse effects were registered. CONCLUSIONS: A fluid fiber mixture and lactulose give comparable results in the treatment of childhood constipation.

Efficacy of cognitive behavioral therapy for adolescents with chronic fatigue syndrome: long-term follow-up of a randomized, controlled trial.

OBJECTIVES: The purpose of this work was to assess the long-term outcome of adolescents with chronic fatigue syndrome who received cognitive behavioral therapy and to determine the predictive value of fatigue severity and physical impairments of the adolescent and the fatigue severity of the mother at baseline for the outcome of the treatment at follow-up. PATIENTS AND METHODS: Sixty-six adolescent patients with chronic fatigue syndrome who previously participated in a randomized, controlled trial that showed that cognitive behavioral therapy was more effective than a waiting-list condition in reducing fatigue and improving physical functioning were contacted for a follow-up assessment. Fifty participants of the follow-up study had received cognitive behavioral therapy for chronic fatigue syndrome (32 formed the cognitive behavioral therapy group in the original trial, and 18 patients received cognitive behavioral therapy after the waiting period). The remaining 16 patients had refused cognitive behavioral therapy after the waiting period. The main outcome measures were fatigue severity (Checklist Individual Strength), physical functioning (Short-Form General Health Survey), and school attendance. RESULTS: Data were complete for 61 patients at follow-up (cognitive behavioral therapy group: 47 patients; no-treatment group: 14 patients). The mean follow-up time was 2.1 years. There was no significant change in fatigue severity between posttreatment and follow-up in the cognitive behavioral therapy group. There was a significant further increase in physical functioning and school attendance (10% increase). The adolescents in the cognitive behavioral therapy group were significantly less fatigued and significantly less functionally impaired and had higher school attendance at follow-up than those in the no-treatment group. Fatigue severity of the mother was a significant predictor of treatment outcome. CONCLUSIONS: The positive effects of cognitive behavioral therapy in adolescents with chronic fatigue syndrome are sustained after cognitive behavioral therapy. Higher fatigue severity of the mother predicts lower treatment outcome in adolescent patients.

Long-term outcome of juvenile idiopathic arthritis following a placebo-controlled trial: sustained benefits of early sulfasalazine treatment.

OBJECTIVES: A previous 24-week randomised trial demonstrated that sulfasalazine (SSZ) treatment was superior to placebo (PLAC) in suppressing disease activity in patients with oligo- and polyarticular onset juvenile idiopathic arthritis (JIA). The current study determines the long-term outcome of the trial participants and evaluates whether the benefits of SSZ allocation are sustained over time. METHODS: Between 2001 and 2003, 32 SSZ and 29 PLAC patients (90% of all patients) were prospectively examined clinically and by chart review, median 9 years (range 7 to 10) after trial inclusion. In the follow-up assessment, variables of the American College of Rheumatology Pediatric 30 (ACR Pedi 30) criteria were collected. The assessor was blinded to trial treatment allocation. RESULTS: After the trial, patients had been routinely followed in rheumatology referral centres, and treated at the discretion of the attending physician. Almost all patients continued or started disease-modifying antirheumatic drugs (DMARDs) (SSZ 91%, PLAC 93%; SSZ treatment in about 80%). DMARD treatment appeared less intensive in the SSZ group as evidenced by a significantly shorter duration of SSZ use (median 2.5 vs 5.2 years; p = 0.02) and a trend towards less use of methotrexate and other DMARDs. More than one-third of the patients reported long periods of non-compliance with DMARD treatment in both groups. At follow-up, 74% of the patients had active joints, and 30% showed active polyarthritis. Almost all outcome scores were better for SSZ compared with PLAC patients. Differences (often exceeding 50%) were significant for the number of active joints, patients' overall well-being, number of patients with episodes of clinical remission off medication (CROM) and duration of these episodes, patients in CROM and ACR Pedi 30 response at follow-up. Additional exploratory analyses performed to detect potential confounders related to patient characteristics or follow-up treatment showed that DMARD treatment compliance was positively correlated with an ACR Pedi 30 response (odds ratio 3.8, 95% confidence interval (CI) 1.1 to 13.4; p = 0.03). Adjusted for compliance, an SSZ patient was 4.2 times as likely as a PLAC patient to be an ACR Pedi 30 responder at follow-up (95% CI 1.3 to 14.3; p = 0.02). CONCLUSIONS: This follow-up study shows that effective suppression of disease activity by SSZ treatment early in active disease in JIA patients has beneficial effects that persist for many years. Given these results, compliance with DMARD treatment deserves serious attention.

Cognitive behaviour therapy for adolescents with chronic fatigue syndrome: randomised controlled trial.

OBJECTIVE: To evaluate the efficacy of cognitive behaviour therapy for adolescents aged 10-17 years with chronic fatigue syndrome. DESIGN: Randomised controlled trial. SETTING: Department of child psychology. PARTICIPANTS: 71 consecutively referred patients with chronic fatigue syndrome; 36 were randomly assigned to immediate cognitive behaviour therapy and 35 to the waiting list for therapy. INTERVENTION: 10 sessions of therapy over five months. Treatment protocols depended on the type of activity pattern (relatively active or passive). All participants were assessed again after five months. MAIN OUTCOME MEASURES: Fatigue severity (checklist individual strength), functional impairment (SF-36 physical functioning), and school attendance. RESULTS: 62 patients had complete data at five months (29 in the immediate therapy group and 33 on the waiting list). Patients in the therapy group reported significantly greater decrease in fatigue severity (difference in decrease on checklist individual strength was 14.5, 95% confidence interval 7.4 to 21.6) and functional impairment (difference in increase on SF-36 physical functioning was 17.3, 6.2 to 28.4) and their attendance at school increased significantly (difference in increase in percentage school attendance was 18.2, 0.8 to 35.5). They also reported a significant reduction in several accompanying symptoms. Self reported improvement was largest in the therapy group. CONCLUSION: Cognitive behaviour therapy is an effective treatment for chronic fatigue syndrome in adolescents.

Development of a standardized method of assessment of radiographs and radiographic change in juvenile idiopathic arthritis: introduction of the Dijkstra composite score.

OBJECTIVE: To evaluate the sensitivity to change of a newly developed radiologic assessment tool, the Dijkstra score, and to develop a numeric composite score and progressor classification scheme to apply in juvenile idiopathic arthritis (JIA) trials. METHODS: A placebo-controlled trial of sulfasalazine (SSZ) in patients with oligoarticular- and polyarticular-onset JIA yielded the data for this study. Data were obtained from 418 sets of radiographs of the clinically involved and contralateral joints (at study entry and at 6 months' followup) from 66 JIA patients. The Dijkstra score assesses the presence or absence of swelling, osteopenia, joint space narrowing, growth abnormalities, subchondral bone cysts, erosions, and malalignment. These signs were combined in the Dijkstra composite score, to assess inflammation (DI), growth (DG), and damage (DD). Progression was defined as an increase in either the DG or the DD score. Scores were evaluated among all radiographs, a standard set of films (hand, foot, and knee), and per patient. All scores were used to explore differences between the 2 treatment groups. RESULTS: Over time, 58% of joints remained normal, 23% remained abnormal but stable, 14% showed an increase in signs, and 5% showed a decrease in signs. Of the 66 JIA patients, 12% had normal radiographic findings throughout followup, 27% showed abnormalities at some sites without change, and 61% showed change in at least 1 site. Changes in the DI, DG, and DD scores varied considerably per type of joint and occurred most frequently in joints of the standard set. DI and DG scores changed most often in the knees, while DD scores changed primarily in the hands and feet. The disease course in 8% of joints was classified as progressive. Films of SSZ-treated patients, versus the placebo group, showed less deterioration by the DD scores (P = 0.04), and the disease course was more often classified as nonprogressive in the SSZ group (P = 0.037). When progressors were defined as those who had at least one radiograph showing progression, significantly more placebo-treated patients were considered progressors (P = 0.046). CONCLUSION: In this trial data set, the Dijkstra composite score and the resulting progressor classification system are comprehensive and feasible tools that are sensitive to change and discriminate between clinical situations. They should now be tested by other investigators and in other data sets.

Inherited multicentric osteolysis with carpal-tarsal localisation mimicking juvenile idiopathic arthritis.

UNLABELLED: Five patients with multicentric carpal-tarsal osteolysis are presented: a mother and her three children with an autosomal dominant mode of inheritance and one of the children with nephropathy, the fifth a sporadic case also with renal involvement. The main findings common to these five patients are symptoms and signs simulating arthritis of the wrists and/or ankles starting at a young age and mimicking juvenile idiopathic arthritis. Early signs of osteolysis and shortening of the carpus or tarsus are radiological characteristic. The disease may be associated with a peculiar face, but most importantly with nephropathy. The pathogenesis is still unknown. CONCLUSION: Recognition of this disease and differentiation from juvenile idiopathic arthritis is important to avoid unnecessary investigations and treatment. Follow-up of renal function is indicated.

Radiologic features in juvenile idiopathic arthritis: a first step in the development of a standardized assessment method.

OBJECTIVE: To describe radiologic features of patients with juvenile idiopathic arthritis (JIA) in a standardized manner, to test the reliability and feasibility of this description, and to correlate these features with clinical signs as a first step in the development of a standardized assessment method. METHODS: The placebo-controlled study of sulfasalazine in patients with oligoarticular, extended oligoarticular, and polyarticular JIA performed by the Dutch Juvenile Idiopathic Arthritis Study Group yielded the data for this study. All trial entry radiographs (clinically involved joints and contralateral joints) were scored (in consensus by a skeletal radiologist and pediatric rheumatologist) for the presence of swelling, osteopenia, joint space narrowing, growth abnormalities, subchondral bone cysts, erosions, and malalignment. RESULTS: Data on 67 of 69 patients were analyzed. The mean age was 9.1 years (range 2.5-17.6 years), and the median disease duration was 24 months (range 5-176 months). Thirteen percent of the patients were IgM rheumatoid factor (IgM-RF) positive, and 16% were HLA-B27 positive. All 68 clinically evaluated joints were included in the maximum of 19 radiographed joints (or joint groups) per patient. The mean number of radiographed joints per patient was 7 (range 2-15); knees, hands, ankles, and feet were most frequently affected. Fifty-eight patients (87%) had radiologic abnormalities in at least one joint (soft-tissue swelling in 63% of patients, growth disturbances in 48%, joint space narrowing in 28%, and erosions in 15%). In total, half of the radiographs of the clinically involved joints showed radiologic abnormalities, including two-thirds of the radiographs of the clinically affected hands and knees. Univariate analysis revealed a good correlation between the overall articular (clinical) severity and the presence of radiologic abnormalities (odds ratio [OR] 1.38, P < 0.0001). Multivariate analysis showed increased ORs for the presence of radiologic abnormalities and IgM-RF positivity (OR 4.6, P = 0.005) or HLA-B27 positivity (OR 3.0, P = 0.004). In general, reproducibility of the radiologic scoring method was good (mean kappa coefficient of 0.74 [range 0.40-0.86]), although there were scoring discrepancies for swelling, osteopenia, and growth disturbances. The scoring took 10-20 minutes per patient. CONCLUSION: Our model of describing and scoring radiologic abnormalities of radiographed joints in JIA was feasible, mostly reproducible, correlated well with the overall articular severity score, and added substantial new information not available on clinical examination.

Growth plate damage, a feature of juvenile idiopathic arthritis, can be induced by adenoviral gene transfer of oncostatin M: a comparative study in gene-deficient mice.

OBJECTIVE: To investigate the involvement of proinflammatory and destructive mediators in oncostatin M (OSM)-induced joint pathology, using gene-deficient mice. METHODS: An adenoviral vector expressing murine OSM was injected into the joints of naive wild-type mice and mice deficient for interleukin-1 (IL-1), IL-6, tumor necrosis factor alpha (TNFalpha), or inducible nitric oxide synthase (iNOS). Reverse transcription-polymerase chain reaction was used to study gene expression. Inflammation and cartilage proteoglycan (PG) depletion were assessed by histology. OSM and IL-1 levels in synovial fluid from patients with juvenile idiopathic arthritis (JIA) were measured by enzyme-linked immunosorbent assay. RESULTS: Adenoviral expression of murine OSM led to joint inflammation, bone apposition, chondrophyte formation, articular cartilage PG depletion, and VDIPEN neoepitope expression in wild-type mice. A unique and consistent observation was the focal PG depletion and disorganization of the growth plate cartilage during the first week of inflammation. Synovial IL-1beta, IL-6, TNFalpha, and iNOS gene expression was strongly induced. Of these factors, only deficiency in IL-1 markedly reduced inflammation and PG depletion and completely prevented growth plate damage. In addition, this is the first study in which OSM was detected in JIA synovial fluid. Most samples were also IL-1beta positive. CONCLUSION: IL-1, but not IL-6, TNFalpha, or iNOS, plays an important role in joint disease induced by intraarticular gene transfer of OSM in mice. The effect of OSM on murine connective tissue and the presence of OSM in human synovial fluid make involvement of OSM in human arthropathies very likely.