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Background: Inhalation therapy with sodium cromoglycate is recommended as the first-line prophylactic treatment for moderate asthma in children. The availability of spacer devices with face-masks has extended the applicability of metered-dose inhalers to younger children. We studied the feasibility and effects of this therapy compared with placebo in children aged 1-4 years.Methods: 218 children aged 1-4 years with moderate asthma were recruited through 151 general practitioners between March, 1995, and March, 1996. They were randomly assigned sodium cromoglycate (10 mg three times daily) or placebo, given by inhaler with spacer device and face-mask for 5 months. Rescue medication (ipratropium plus fenoterol aerosol) was available during the baseline period of 1 month and the intervention period. Parents completed a daily symptom-score list. The primary outcome measure was the proportion of symptom-free days in months 2 to 5. Analysis was by both intention to treat and on treatment.Findings: 167 (77%) children completed the trial. 131 (78%) of these children used at least 80% of the recommended dose. Of the 51 children who stopped prematurely, 23 had difficulties with inhaled treatment. The mean proportion of symptom-free days for both groups was greater for the treatment period than for the baseline period (95% CI for mean difference 5.1 to 17.5 cromoglycate, 11.9 to 23.3 placebo). However there were no differences between the sodium cromoglycate and placebo groups in the proportion of symptom-free days (mean 65.7 [SD 25.3] vs 64.3 [24.5]%; 95% CI for difference -8.46 to 5.70) or in any other outcome measure.Interpretation: Our study in a general practice setting shows that inhalation therapy with a spacer device and face-mask is feasible in a majority of children below the age of 4 years. However, long-term prophylactic therapy with inhaled sodium cromoglycate is not more effective than placebo in this age-group. [ABSTRACT FROM AUTHOR]

Background: Pulled elbow (nursemaid's elbow) is a common injury in young children. It often results from a sudden pull on the arm, usually by an adult or taller person, which pulls the radius through the annular ligament, resulting in subluxation (partial dislocation) of the radial head. It can also be caused by a fall or twist. The child experiences sudden acute pain and loss of function in the affected arm. Pulled elbow is usually treated by manual reduction of the subluxed radial head. Various manoeuvres can be applied; most commonly, supination of the forearm, often combined with flexion, and (hyper-)pronation. It is unclear which is most successful. This is an update of a Cochrane review first published in 2009 and last updated in 2011., Objectives: To compare the effects (benefits and harms) of the different methods used to manipulate pulled elbow in young children., Search Methods: We searched the Cochrane Bone, Joint and Muscle Trauma Group Specialised Register, the Cochrane Central Register of Controlled Trials, MEDLINE, Embase, CINAHL, LILACS, PEDro, clinical trial registers and reference lists of articles. Date of last search: September 2016., Selection Criteria: Randomised or quasi-randomised controlled clinical trials evaluating manipulative interventions for pulled elbow were included. Our primary outcome was failure at the first attempt, necessitating further treatment., Data Collection and Analysis: Two review authors independently evaluated trials for inclusion, assessed risk of bias, and extracted data. We pooled data using a fixed-effect model., Main Results: Overall, nine trials with 906 children (all younger than seven years old and 58% of whom were female) were included, of which five trials were newly identified in this update. Eight trials were performed in emergency departments or ambulatory care centres, and one was performed in a tertiary paediatric orthopaedic unit. Four trials were conducted in the USA, three in Turkey, one in Iran, and one in Spain. Five trials were at high risk of selection bias because allocation was not concealed and all trials were at high risk of detection bias due to the lack of assessor blinding. Eight trials compared hyperpronation with supination-flexion. We found low-quality evidence that hyperpronation resulted in less failure at first attempt than supination-flexion (9.2% versus 26.4%, risk ratio (RR) 0.35; 95% confidence interval (CI) 0.25 to 0.50; 811 participants, 8 studies). Based on an illustrative risk of 268 failures at first attempt per 1000 children treated using supination-flexion, this amounted to 174 fewer failures per 1000 children treated using hyperpronation (95% CI 134 to 201 fewer). Based on risk differences data, we also estimated a number needed to treat of 6 (95% CI 5 to 8); this means that six children would need to be treated with the hyperpronation method rather than the supination-flexion method to avoid one additional failure at the first attempt.The very low-quality evidence (from four studies) for pain during or after manipulation means that it is uncertain whether there is or is not a difference between pronation and supination-flexion. There was very low-quality evidence from six studies that repeat pronation may be more effective than repeat supination-flexion for the second attempt after initial failure. The remaining outcomes were either not reported (adverse effects, recurrence) or unsuitable for pooling (ultimate failure). Ultimate failure, reported for the overall population only because of the differences in the study protocols with respect to what to do after the first attempt failed, ranged from no ultimate failures in two studies to six failures (4.1% of 148 episodes) in one study.One trial compared supination-extension versus supination-flexion. It provided very low-quality evidence (downgraded three levels for very serious risk of bias and serious imprecision) of no clear difference in failure at first attempt between the two methods., Authors' Conclusions: There was low-quality evidence from eight small trials that the pronation method may be more effective at first attempt than the supination method for manipulating pulled elbow in young children. For other outcomes, no conclusions could be drawn either because of very low-quality evidence or the outcomes not being reported. We suggest that a high-quality randomised clinical trial comparing hyperpronation and supination-flexion is required to provide definitive evidence. We recommend that this is preceded by a survey among clinicians to establish the extent of clinical equipoise and to optimise the study design and recruitment.

Background: Molluscum contagiosum is a common skin infection that is caused by a pox virus and occurs mainly in children. The infection usually resolves within months in people without immune deficiency, but treatment may be preferred for social and cosmetic reasons or to avoid spreading the infection. A clear evidence base supporting the various treatments is lacking.This is an update of a Cochrane Review first published in 2006, and updated previously in 2009., Objectives: To assess the effects of specific treatments and management strategies, including waiting for natural resolution, for cutaneous, non-genital molluscum contagiosum in people without immune deficiency., Search Methods: We updated our searches of the following databases to July 2016: the Cochrane Skin Group Specialised Register, CENTRAL, MEDLINE, Embase, and LILACS. We searched six trial registers and checked the reference lists of included studies and review articles for further references to relevant randomised controlled trials. We contacted pharmaceutical companies and experts in the field to identify further relevant randomised controlled trials., Selection Criteria: Randomised controlled trials of any treatment of molluscum contagiosum in people without immune deficiency. We excluded trials on sexually transmitted molluscum contagiosum and in people with immune deficiency (including those with HIV infection)., Data Collection and Analysis: Two review authors independently selected studies, assessed methodological quality, and extracted data from selected studies. We obtained missing data from study authors where possible., Main Results: We found 11 new studies for this update, resulting in 22 included studies with a total of 1650 participants. The studies examined the effects of topical (20 studies) and systemic interventions (2 studies).Among the new included studies were the full trial reports of three large unpublished studies, brought to our attention by an expert in the field. They all provided moderate-quality evidence for a lack of effect of 5% imiquimod compared to vehicle (placebo) on short-term clinical cure (4 studies, 850 participants, 12 weeks after start of treatment, risk ratio (RR) 1.33, 95% confidence interval (CI) 0.92 to 1.93), medium-term clinical cure (2 studies, 702 participants, 18 weeks after start of treatment, RR 0.88, 95% CI 0.67 to 1.14), and long-term clinical cure (2 studies, 702 participants, 28 weeks after start of treatment, RR 0.97, 95% CI 0.79 to 1.17). We found similar but more certain results for short-term improvement (4 studies, 850 participants, 12 weeks after start of treatment, RR 1.14, 95% CI 0.89 to 1.47; high-quality evidence). For the outcome 'any adverse effect', we found high-quality evidence for little or no difference between topical 5% imiquimod and vehicle (3 studies, 827 participants, RR 0.97, 95% CI 0.88 to 1.07), but application site reactions were more frequent in the groups treated with imiquimod (moderate-quality evidence): any application site reaction (3 studies, 827 participants, RR 1.41, 95% CI 1.13 to 1.77, the number needed to treat for an additional harmful outcome (NNTH) was 11); severe application site reaction (3 studies, 827 participants, RR 4.33, 95% CI 1.16 to 16.19, NNTH over 40).For the following 11 comparisons, there was limited evidence to show which treatment was superior in achieving short-term clinical cure (low-quality evidence): 5% imiquimod less effective than cryospray (1 study, 74 participants, RR 0.60, 95% CI 0.46 to 0.78) and 10% potassium hydroxide (2 studies, 67 participants, RR 0.65, 95% CI 0.46 to 0.93); 10% Australian lemon myrtle oil more effective than olive oil (1 study, 31 participants, RR 17.88, 95% CI 1.13 to 282.72); 10% benzoyl peroxide cream more effective than 0.05% tretinoin (1 study, 30 participants, RR 2.20, 95% CI 1.01 to 4.79); 5% sodium nitrite co-applied with 5% salicylic acid more effective than 5% salicylic acid alone (1 study, 30 participants, RR 3.50, 95% CI 1.23 to 9.92); and iodine plus tea tree oil more effective than tea tree oil (1 study, 37 participants, RR 0.20, 95% CI 0.07 to 0.57) or iodine alone (1 study, 37 participants, RR 0.07, 95% CI 0.01 to 0.50). Although there is some uncertainty, 10% potassium hydroxide appears to be more effective than saline (1 study, 20 participants, RR 3.50, 95% CI 0.95 to 12.90); homeopathic calcarea carbonica appears to be more effective than placebo (1 study, 20 participants, RR 5.57, 95% CI 0.93 to 33.54); 2.5% appears to be less effective than 5% solution of potassium hydroxide (1 study, 25 participants, RR 0.35, 95% CI 0.12 to 1.01); and 10% povidone iodine solution plus 50% salicylic acid plaster appears to be more effective than salicylic acid plaster alone (1 study, 30 participants, RR 1.43, 95% CI 0.95 to 2.16).We found no statistically significant differences for other comparisons (most of which addressed two different topical treatments). We found no randomised controlled trial evidence for expressing lesions or topical hydrogen peroxide.Study limitations included no blinding, many dropouts, and no intention-to-treat analysis. Except for the severe application site reactions of imiquimod, none of the evaluated treatments described above were associated with serious adverse effects (low-quality evidence). Among the most common adverse events were pain during application, erythema, and itching. Included studies of the following comparisons did not report adverse effects: calcarea carbonica versus placebo, 10% povidone iodine plus 50% salicylic acid plaster versus salicylic acid plaster, and 10% benzoyl peroxide versus 0.05% tretinoin.We were unable to judge the risk of bias in most studies due to insufficient information, especially regarding concealment of allocation and possible selective reporting. We considered five studies to be at low risk of bias., Authors' Conclusions: No single intervention has been shown to be convincingly effective in the treatment of molluscum contagiosum. We found moderate-quality evidence that topical 5% imiquimod was no more effective than vehicle in terms of clinical cure, but led to more application site reactions, and high-quality evidence that there was no difference between the treatments in terms of short-term improvement. However, high-quality evidence showed a similar number of general side effects in both groups. As the evidence found did not favour any one treatment, the natural resolution of molluscum contagiosum remains a strong method for dealing with the condition.

Background: Combination therapy with prednisone or etanercept may induce earlier and/or more improvement in disease activity in Disease Modifying Anti Rheumatic Drug (DMARD) naïve non-systemic Juvenile Idiopathic Arthritis (JIA) patients. Here we present three months clinical outcome of initial treatments of the BeSt-for-Kids study., Methods: Included patients were randomized to either: 1. initial DMARD-monotherapy (sulfasalazine (SSZ) or methotrexate (MTX)), 2. Initial MTX / prednisolone-bridging, 3. Initial combination MTX/etanercept. Percentage inactive disease, adjusted (a) ACR Pedi30, 50 and 70 and JADAS after 6 and 12 weeks of treatment (intention to treat analysis) and side effects are reported., Results: 94 patients (67% girls, 32 (arm 1), 32 (arm 2) and 30 (arm 3) with median (InterQuartileRange) age of 9.1 (4.7-12.9) years were included. 38% were ANA positive, 10 had oligo-articular disease, 68 polyarticular JIA and 16 psoriatic arthritis. Baseline median (IQR) ACRpedi-scores: VAS physician 49 (40-58) mm, VAS patient 54 (37-70) mm, ESR 6.5 (2-14.8)mm/hr, active joint count 8 (5-12), limited joint count 3 (1-5), CHAQ score 0.88 (0.63-1.5). In arm 1, 17 started with MTX, 15 with SSZ. After 3 months, aACR Pedi 50 was reached by 10/32 (31%), 12/32(38%) and 16/30 (53%) (p = 0.19) and aACR Pedi 70 was reached by 8/32 (25%), 6/32(19%) and 14/30(47%) in arms 1-3 (p = 0.04). Toxicity was similar. Few serious adverse events were reported., Conclusion: After 3 months of treatment in a randomized trial, patients with recent-onset JIA achieved significantly more clinical improvement (aACRPedi70) on initial combination therapy with MTX / etanercept than on initial MTX or SSZ monotherapy., Trial Registration: NTR1574 . Registered 3 December 2008.

Objective: To carry out a longitudinal investigation of functional outcome, health-related quality of life (HRQoL) and treatment strategies in JIA patients who started etanercept >5 years ago., Methods: We approached patients whose HRQoL changes were described previously in a subanalysis of the Dutch Arthritis and Biologicals in Children register. Recent disease status, co-morbidities and structural damage were retrieved. Disability and HRQoL were assessed by (Childhood) HAQ [(C)HAQ], Child Health Questionnaire, Short Form 36 and Health Utilities Index Mark 3. Changes over time were analysed with linear mixed models., Results: Forty-three patients (81% response) started etanercept a median 8.5 years ago. At the time of this long-term analysis, median age was 22 years (interquartile range: 18-24 years). HRQoL outcome was similar to HRQoL 15-27 months after the initiation of etanercept; 42% had a (C)HAQ of 0.00 and 67% had achieved inactive disease. Patients reported increasing levels of bodily pain compared with earlier measurements. Unemployment (12%) was comparable to the general population; educational level was higher. Use of biologic agents was as follows: 40% etanercept; 40% other biologic agents; and 20% none. Joint surgery occurred in 14% of patients., Conclusion: At a median 8.5 years after the commencement of etanercept treatment, JIA patients maintain most of the acquired improvement in HRQoL. Although disability and disease activity are low, chronic pain remains an issue. Persistence and possible deterioration of radiological damage emphasize the importance of early treatment. The fact that 20% of patients do not use any anti-rheumatic medication shows that clinical remission of medication might be an achievable goal., (© The Author 2015. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Objectives: Juvenile idiopathic arthritis (JIA) affects bone mineral density (BMD). Dual-energy X-ray absorptiometry (DXA) is the most widely used technique to determine BMD. Digital X-ray radiogrammetry (DXR) is a feasible method for determination of cortical BMD on hand radiographs. This study aimed to compare DXR and DXA in the assessment of BMD in JIA patients., Methods: Thirty-five JIA patients with available DXA and hand radiograph within the same time period were included from the Dutch Arthritis and Biologicals in Children register. Outcome measures for BMD were Bone Health Index from DXR and BMD total body, BMD lumbar spine and Bone Mineral Apparent Density from DXA. All measures were transformed to Z-scores. Correlations were assessed with Pearson correlation coefficients., Results: Median age of the patients (60% female) was 11.7 years. Pearson correlation coefficient was significant for the absolute scores: 0.568-0.770 (p<0.001). No significant correlation was found between the Z-scores of DXA and DXR., Conclusions: The BMD assessment from the DXR was correlated to DXA measures in a cohort of JIA patients, although only in absolute scores. Future steps for implementation of DXR in clinical practice include evaluation of responsiveness to change, predictive value and comparison with other imaging techniques., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

Introduction: Approximately 30% of juvenile idiopathic arthritis (JIA) patients fail to respond to anti-TNF treatment. When clinical remission is induced, some patients relapse after treatment has been stopped. We tested the predictive value of MRP8/14 serum levels to identify responders to treatment and relapse after discontinuation of therapy., Methods: Samples from 88 non-systemic JIA patients who started and 26 patients who discontinued TNF-blockers were analyzed. MRP8/14 serum levels were measured by in-house MRP8/14 ELISA and by Bühlmann Calprotectin ELISA at start of anti-TNF treatment, within 6 months after start and at discontinuation of etanercept in clinical remission. Patients were categorized into responders (ACRpedi ≥ 50 and/or inactive disease) and non-responders (ACRpedi < 50) within six months after start, response was evaluated by change in JADAS-10. Disease activity was assessed within six months after discontinuation., Results: Baseline MRP8/14 levels were higher in responders (median MRP8/14 of 1466 ng/ml (IQR 1045-3170)) compared to non-responders (median MRP8/14 of 812 (IQR 570-1178), p < 0.001). Levels decreased after start of treatment only in responders (p < 0.001). Change in JADAS-10 was correlated with baseline MRP8/14 levels (Spearman's rho 0.361, p = 0.001). Patients who flared within 6 months after treatment discontinuation had higher MRP8/14 levels (p = 0.031, median 1025 ng/ml (IQR 588-1288)) compared to patients with stable remission (505 ng/ml (IQR 346-778)). Results were confirmed by Bühlmann ELISA with high reproducibility but different overall levels., Conclusion: High levels of baseline MRP8/14 are associated with good response to anti-TNF treatment, whereas elevated MRP8/14 levels at discontinuation of etanercept are associated with higher chance to flare.

Background: Treatment of juvenile idiopathic arthritis (JIA) has changed dramatically since the introduction of biological agents in 1999., Objective: To evaluate trends in prescription patterns of biological agents and the subsequent outcome of JIA., Methods: The Arthritis and Biologics in Children register (multicentre prospective observational study) aimed to include all consecutive patients with JIA in the Netherlands who had started biological agents since 1999. Patients were divided according to year of introduction of first biological agent. Patient characteristics at introduction of the first biological agent and its effectiveness were analysed over 12 years., Results: 335 patients with non-systemic JIA and 86 patients with systemic JIA started a biological agent between 1999 and 2010. Etanercept remained the most often prescribed biological agent for non-systemic JIA; anakinra became first choice for systemic JIA. The use of systemic glucocorticoids and synthetic disease-modifying antirheumatic drugs before biological agents decreased. During these 12 years of observation, biological agents were prescribed earlier in the disease course and to patients with lower baseline JADAS (Juvenile Arthritis Disease Activity Score) disease activity. All baseline disease activity parameters were lowered in patients with non-systemic JIA. In systemic JIA, prescription patterns changed towards very early introduction of biological agents (median 0.4 years of disease duration) in patients with a low number of joints with active arthritis and high erythrocyte sedimentation rates. These changes for both systemic and non-systemic JIA resulted in more patients with inactive disease after 3 and 15 months of treatment., Conclusions: Biological agents are increasingly prescribed, earlier in the disease and in patients with JIA with lower disease activity. These changes are accompanied by better short-term disease outcomes., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)

Objective: To evaluate the reliability of a manikin format, patient-reported joint count in juvenile idiopathic arthritis (JIA), and to detect changes in agreement at a second visit., Methods: Patients with JIA aged 12-21 were asked to mark joints with active arthritis on a manikin before their regular clinic visit. The physician then performed a joint count without having seen the patient's assessment. Agreement between scores of physician-reported and patient-reported joint counts was assessed using ICC. Kappa statistics were used to assess reliability of scoring individual joints., Results: The study included 75 patients with JIA. In general, patients had a low number of active joints (median 1 joint, indicated by the physician). ICC was moderate (0.61) and κ ranged from 0.3-0.7. At the second visit, κ were similar; the ICC was 0.19. When a patient scored 0 joints, the physician confirmed this 93%-100% of the time. When the patient marked ≥ 1 joints, the physician confirmed arthritis 59%-76% of the time. Sensitivity to change was moderate., Conclusion: Agreement between physician and patient on the number of joints with active arthritis was reasonable. Untrained patients tended to overestimate the presence of arthritis when they marked active joints on a manikin-format joint count. When the patient indicated absence of arthritis, the physician usually confirmed this. As the agreement did not improve at followup, future research should focus on the possibility of achieving this through training. For now, the patient-reported joint count cannot replace the physicians' joint count in clinical practice; it may be used in epidemiological studies with caution.

Introduction: Chronic inflammation combined with glucocorticoid treatment and immobilization puts juvenile idiopathic arthritis (JIA) patients at risk of impaired growth and reduced bone mineral density (BMD). Conventional methods for evaluating bone age and BMD are time-consuming or come with additional costs and radiation exposure. In addition, an automated measurement of bone age and BMD is likely to be more consistent than visual evaluation. In this study, we aimed to evaluate the feasibility of an automated method for determination of bone age and (cortical) bone mineral density (cBMD) in severely affected JIA patients. A secondary objective was to describe bone age and cBMD in this specific JIA population eligible for biologic treatment., Methods: In total, 69 patients with standard hand radiographs at the start of etanercept treatment and of calendar age within the reliability ranges (2.5 to 17 years for boys and 2 to 15 years for girls) were extracted from the Dutch Arthritis and Biologicals in Children register. Radiographs were analyzed using the BoneXpert method, thus automatically determining bone age and cBMD expressed as bone health index (BHI). Agreement between measurements of the left- and right-hand radiographs and a repeated measurement of the left hand were assessed with the intraclass correlation coefficient (ICC). Regression analysis was used to identify variables associated with Z-scores of bone age and BHI., Results: The BoneXpert method was reliable in the evaluation of radiographs of 67 patients (radiographs of 2 patients were rejected because of poor image quality). Agreement between left- and right-hand radiographs (ICC = 0.838 to 0.996) and repeated measurements (ICC = 0.999 to 1.000) was good. Mean Z-scores of bone age (-0.36, P = 0.051) and BHI (-0.85, P < 0.001) were lower compared to the healthy population. Glucocorticoid use was associated with delayed bone age (0.79 standard deviation (SD), P = 0.028), and male gender was associated with a lower Z-score of BHI (0.65 SD, P = 0.021)., Conclusions: BoneXpert is an easy-to-use method for assessing bone age and cBMD in patients with JIA, provided that radiographs are of reasonable quality and patients' bone age lies within the age ranges of the program. The population investigated had delayed bone maturation and lower cBMD than healthy children.

Objective: Over the past decade, the availability of biological agents for the treatment of juvenile idiopathic arthritis (JIA) has increased substantially. Because direct head-to-head trials comparing these agents are lacking, we indirectly compared their efficacy., Methods: In a systematic review, all available efficacy data from randomised controlled trials performed in JIA with inclusion of biological agents were retrieved. Indirect between-drug comparisons (based on Bucher's method) were conducted only if trials were comparable with regard to design and patients' characteristics related to treatment outcome., Results: We identified 11 randomised controlled trials. On the basis of the equality of the trials, six trials were grouped into two networks of evidence. Network 1 included withdrawal trials which evaluated etanercept, adalimumab and abatacept in polyarticular course JIA. Indirect comparisons identified no significant differences in short-term efficacy. Network 2 indirectly compared trials with a parallel study design investigating anakinra, tocilizumab and canakinumab in systemic JIA; no differences in comparative efficacy were identified. Although the two networks were constructed on the basis of comparability, small differences in trial design and case mix still existed., Conclusions: Because of the small number of trials and the observed differences between trials, no definite conclusions could be drawn about the comparative effectiveness of the indirectly compared biological agents. Therefore, for now, the paediatric rheumatologist has to rely on observational data and safety, practical and financial arguments. Comparability of future trials needs to be improved, and head-to-head trials are required to decide on the best biological treatment for JIA.

Objectives: To evaluate differences in baseline characteristics between etanercept- and adalimumab-treated JIA patients and to reveal factors that influence the choice between these TNF inhibitors, which are considered equally effective in the recent ACR recommendations for JIA treatment., Methods: Biologic-naïve JIA patients with active arthritis who started treatment with adalimumab or etanercept between March 2008 and December 2011 were selected from the Dutch Arthritis and Biologicals in Children register. Baseline characteristics were compared. Focus group interviews with paediatric rheumatologists were performed to evaluate factors determining treatment choices., Results: A total of 193 patients started treatment with etanercept and 21 with adalimumab. Adalimumab-treated patients had longer disease duration prior to the start of biologics (median 5.7 vs 2.0 years) and more often a history of uveitis (71% vs 4%). Etanercept-treated patients had more disability at baseline (median Childhood Health Assessment Questionnaire score 1.1 vs 0.4) and more active arthritis (median number of active joints 6 vs 4). The presence of uveitis was the most important factor directing the choice towards adalimumab. Factors specific for the paediatric population-such as painful adalimumab injections-as well as the physician's familiarity with the drug accounted for the preference for etanercept., Conclusion: Although the two TNF inhibitors are considered equally effective, in daily practice etanercept is most often prescribed; adalimumab is mainly preferred when uveitis is present. In choosing the most suitable biologic treatment, paediatric rheumatologists take into account drug and patient factors, considering newly published data and cautiously implementing this into daily care.

Biologics are a promising treatment option for juvenile idiopathic arthritis (JIA) but drug costs are very high compared to conventional treatment. From a socioeconomic view the additional costs of new interventions should be weighed against their incremental health benefits compared to standard care. Therefore we evaluated data on cost-effectiveness of biologics in JIA. We searched Medline, Embase, and The York Centre for Reviews and Dissemination database for relevant literature. Current data show that biologics are reducing direct and indirect healthcare costs if one excludes the costs of the drug itself. The costs of biologics are more than ten times as high as conventional drug treatment. As a result of limited data, no comparison on cost-effectiveness between biologics could be performed. Although data on long-term cost-effectiveness of biologics are lacking, the expectation is that they will be cost-effective in the long-term. The idea behind this is that biologic treatment should be administered to patients that without these drugs would incur high direct and indirect costs due to continuous severe disease resulting in irreversible disabilities. In our opinion the best cost benefit could be gained if these patients receive biologic treatment introduced early in the disease. This is in order to minimize irreversible damage to the joints and minimize need for long-term biologic therapy by early suppression of the disease. To support these hypotheses future research is needed on long-term cost-effectiveness of all biologics used in JIA.

Objective: To evaluate the effectiveness and safety of switching to a second or third biological agent in juvenile idiopathic arthritis (JIA) after etanercept failure., Methods: The Arthritis and Biologicals in Children Register aims to include all Dutch JIA patients who have used biological agents. Data on the disease course were used to estimate drug survival with Kaplan-Meier and calculate adverse event (AE) rates., Results: Of 307 biologically naive JIA patients who started etanercept, 80 (26%) switched to a second and 22 (7%) to a third biological agent. During 1030 patient-years of follow-up after the introduction of etanercept, 49 switches to adalimumab, 28 infliximab, 17 anakinra, four abatacept and four trial drugs were evaluated. 84% (95% CI 80% to 88%) of patients who started etanercept as a first biological agent were, after 12 months, still on the drug, compared with 47% (95% CI 35% to 60%) who started a second and 51% (95% CI 26% to 76%) who started a third biological agent. Patients who switched because of primary ineffectiveness continued the second agent less often (32%, 95% CI 12% to 53%). After etanercept failure, drug continuation of adalimumab was similar to infliximab for patients with non-systemic JIA; anakinra was superior to a second TNF-blocker for systemic JIA. AE rates within first 12 months after initiation were comparable for each course and each biological agent., Conclusions: Switching to another biological agent is common, especially for systemic JIA patients. A second (and third) agent was less effective than the first. The choice of second biological agent by the physician mainly depends on availability and JIA category.

Objective: Because TNF inhibitors are not approved for persistent oligoarticular JIA (oJIA), although they are used off-label, we evaluated their effectiveness in patients in this category., Methods: Persistent oJIA patients were selected from the Dutch Arthritis and Biologicals in Children (ABC) register, an ongoing multicentre prospective study that aims to include all Dutch children with JIA using biologic agents. Response was assessed by the JIA core-set disease activity variables and modified Wallace criteria for inactive disease., Results: Until February 2011, 16 persistent oJIA patients (68.8% females) had been included in the register. Median age of onset was 8.4 years [interquartile range (IQR) 2.1-13.5 years]; history of uveitis in 18.8%; ANA-positive 56.3%. All had previously used MTX, and 81.3% had used IA CSs. Median follow-up after the introduction of biologic treatment was 13.7 months (IQR 8.3-16.7 months). Fourteen patients started etanercept and two patients who had active arthritis as well as uveitis started adalimumab. Although patients with persistent oJIA had few affected joints [median of two active joints at the start of biologic (IQR 1-3)], the patient/parent assessments of pain [median visual analogue score (VAS) 51 (IQR 1-64)] and well-being [median VAS 44 (IQR 6-66)] were high. Additionally, their physician evaluated the disease activity as moderately high [median VAS 36 (IQR 4-65)]. After 3 months this decreased to 0 (IQR 0-30) and 63% achieved inactive disease. After 15 months the disease was inactive in 9/10 observed patients. TNF inhibitors were tolerated well., Conclusion: TNF blocking agents seem an effective and justifiable option in persistent oJIA when treatment with IA CS injections and MTX has failed.

Background: Analysis of myeloid-related protein 8 and 14 complex (MRP8/14) serum concentrations is a potential new tool to support the diagnosis of systemic-onset juvenile idiopathic arthritis (SJIA) in the presence of fever of unknown origin., Objective: To test the ability of MRP8/14 serum concentrations to monitor disease activity in patients with SJIA and stratify patients at risk of relapse., Methods: Serum concentrations of MRP8/14 in 52 patients with SJIA were determined by a sandwich ELISA. The monitoring of therapeutic regimens targeting interleukin 1 and tumour necrosis factor α, and methotrexate treatment was analysed and diagnostic power to predict flares was tested., Results: MRP8/14 levels were clearly raised in active disease and decreased significantly in response to successful treatments. Serum concentrations of MRP8/14 increased significantly (p<0.001) (mean±95% CI 12.030±3.090 ng/ml) during disease flares compared with patients with inactive disease (864±86 ng/ml). During clinical remission MRP8/14 serum levels of >740 ng/ml predicted disease flares accurately (sensitivity 92%, specificity 88%). MRP8/14 levels correlated well with clinical disease activity, as assessed by physician's global assessment of disease activity (r=0.62), Childhood Health Assessment Questionnaire (r=0.56), active joint count (r=0.46) and with C-reactive protein (r=0.71) and erythrocyte sedimentation rate (r=0.72) (for all p<0.001)., Conclusion: MRP8/14 serum concentrations correlate closely with response to drug treatment and disease activity and therefore might be an additional measurement for monitoring anti-inflammatory treatment of individual patients with SJIA. MRP8/14 serum concentrations are the first predictive biomarker indicating subclinical disease activity and stratifying patients at risk of relapse during times of clinically inactive disease.

Background: Pulled elbow (nursemaid's elbow) is a common injury in young children. It results from a sudden pull on the arm, usually by an adult or taller person, which pulls the radius through the annular ligament, resulting in subluxation (partial dislocation) of the radial head. The child experiences sudden acute pain and loss of function in the affected arm. Pulled elbow is usually treated by manual reduction of the subluxed radial head. Various manoeuvres can be applied. Most textbooks recommend supination of the forearm, as opposed to pronation and other approaches. It is unclear which manoeuvre is most successful. This is an update of a Cochrane review first published in 2009., Objectives: The objective of this review is to compare the effectiveness and painfulness of the different methods used to manipulate pulled elbow in young children., Search Methods: We searched the Cochrane Bone, Joint and Muscle Trauma Group Specialised Register, the Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE, CINAHL, LILACS, PEDro, clinical trial registers and reference lists of articles. Date of last search: July 2011., Selection Criteria: Any randomised or quasi-randomised controlled clinical trials evaluating manipulative interventions for pulled elbow were included. Our primary outcome was failure at the first attempt, necessitating further treatment., Data Collection and Analysis: Two review authors independently evaluated trials for inclusion and, for the included trials, independently assessed the risk of bias and extracted data., Main Results: One trial with 66 children was newly included in this update. Overall, four trials with 379 children, all younger than seven years old, were included. All four trials compared pronation versus supination. One trial was at high risk of selection bias because allocation was not concealed and all four trials were at high risk of detection bias due to the lack of assessor blinding. Pronation resulted in statistically significantly less failure than supination (21/177 versus 47/181, risk ratio 0.45; 95% confidence interval 0.28 to 0.73). Pain perception was reported by two trials but data were unavailable for pooling. Both studies concluded that the pronation technique was less painful than the supination technique., Authors' Conclusions: There is limited evidence from four small low-quality trials that the pronation method might be more effective and less painful than the supination method for manipulating pulled elbow in young children. We recommend that a high quality randomised trial be performed to strengthen the evidence.

Background: Impetigo is a common, superficial bacterial skin infection, which is most frequently encountered in children. There is no generally agreed standard therapy, and guidelines for treatment differ widely. Treatment options include many different oral and topical antibiotics as well as disinfectants. This is an updated version of the original review published in 2003., Objectives: To assess the effects of treatments for impetigo, including non-pharmacological interventions and 'waiting for natural resolution'., Search Methods: We updated our searches of the following databases to July 2010: the Cochrane Skin Group Specialised Register, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE (from 2005), EMBASE (from 2007), and LILACS (from 1982). We also searched online trials registries for ongoing trials, and we handsearched the reference lists of new studies found in the updated search., Selection Criteria: Randomised controlled trials of treatments for non-bullous, bullous, primary, and secondary impetigo., Data Collection and Analysis: Two independent authors undertook all steps in data collection. We performed quality assessments and data collection in two separate stages., Main Results: We included 57 trials in the first version of this review. For this update 1 of those trials was excluded and 12 new trials were added. The total number of included trials was, thus, 68, with 5578 participants, reporting on 50 different treatments, including placebo. Most trials were in primary impetigo or did not specify this.For many of the items that were assessed for risk of bias, most studies did not provide enough information. Fifteen studies reported blinding of participants and outcome assessors.Topical antibiotic treatment showed better cure rates than placebo (pooled risk ratio (RR) 2. 24, 95% confidence interval (CI) 1.61 to 3.13) in 6 studies with 575 participants. In 4 studies with 440 participants, there was no clear evidence that either of the most commonly studied topical antibiotics (mupirocin and fusidic acid) was more effective than the other (RR 1.03, 95% CI 0.95 to 1.11).In 10 studies with 581 participants, topical mupirocin was shown to be slightly superior to oral erythromycin (pooled RR 1.07, 95% CI 1.01 to 1.13). There were no significant differences in cure rates from treatment with topical versus other oral antibiotics. There were, however, differences in the outcome from treatment with different oral antibiotics: penicillin was inferior to erythromycin, in 2 studies with 79 participants (pooled RR 1.29, 95% CI 1.07 to 1.56), and cloxacillin, in 2 studies with 166 participants (pooled RR 1.59, 95% CI 1.21 to 2.08).There was a lack of evidence for the benefit of using disinfectant solutions. When 2 studies with 292 participants were pooled, topical antibiotics were significantly better than disinfecting treatments (RR 1.15, 95% CI 1.01 to 1.32).The reported number of side-effects was low, and most of these were mild. Side-effects were more common for oral antibiotic treatment compared to topical treatment. Gastrointestinal effects accounted for most of the difference.Worldwide, bacteria causing impetigo show growing resistance rates for commonly used antibiotics. For a newly developed topical treatment, retapamulin, no resistance has yet been reported., Authors' Conclusions: There is good evidence that topical mupirocin and topical fusidic acid are equally, or more, effective than oral treatment. Due to the lack of studies in people with extensive impetigo, it is unclear if oral antibiotics are superior to topical antibiotics in this group. Fusidic acid and mupirocin are of similar efficacy. Penicillin was not as effective as most other antibiotics. There is a lack of evidence to support disinfection measures to manage impetigo.

Context: Since the introduction of biologic therapies, the pharmacological treatment approach for juvenile idiopathic arthritis (JIA) has changed substantially, with achievement of inactive disease as a realistic goal., Objective: To determine the response to therapy after initiation of etanercept therapy among patients with JIA and to examine the association between baseline factors and response to etanercept treatment., Design, Setting, and Patients: The Arthritis and Biologicals in Children Register, an ongoing prospective observational study since 1999, includes all Dutch JIA patients who used biologic agents. All biologically naive patients who started etanercept before October 2009 were included, with follow-up data to January 2011. Among the 262 patients, 185 (71%) were female, 46 (18%) had systemic-onset, and the median age at initiation of etanercept treatment was 12.4 years., Main Outcome Measures: Excellent response (inactive disease or discontinuation earlier due to disease remission), intermediate response (more than 50% improvement from baseline, but no inactive disease), and poor response (less than 50% improvement from baseline or discontinuation earlier due to ineffectiveness or intolerance) evaluated 15 months after initiation of etanercept., Results: At 15 months after treatment initiation, 85 patients (32%) were considered excellent responders; 92 (36%), intermediate responders; and 85 (32%), poor responders. Compared with an intermediate or poor response, an excellent response was associated with lower baseline disability score (range, 0-3 points, with 0 being the best score; adjusted odds ratio [OR] per point increase, 0.49; 95% CI, 0.33-0.74); fewer disease-modifying antirheumatic drugs (DMARD) (including methotrexate) used before initiating etanercept (adjusted OR per DMARD used, 0.64; 95% CI, 0.43-0.95), and younger age at onset (adjusted OR per year increase, 0.92; 95% CI, 0.84-0.99). Compared with an intermediate or excellent response, a poor response was associated with systemic JIA (adjusted OR systemic vs nonsystemic categories, 2.92; 95% CI, 1.26-6.80), and female sex (adjusted OR female vs male, 2.16; 95% CI, 1.12-4.18). Within the first 15 months of etanercept treatment, 119 patients experienced 1 or more infectious, noninfectious, or serious adverse events, including 37 among those with an excellent response, 36 with an intermediate response, and 46 with a poor response. Within the first 15 months of treatment, 61 patients discontinued etanercept treatment, including 4 with an excellent response, 0 with an intermediate response, and 57 with a poor response. In a secondary analysis of 262 patients with a median follow-up of 35.6 months after initiation of etanercept, a range of 37% to 49% of patients reached inactive disease. The mean adherence to etanercept was 49.2 months (95% CI, 46.4-52.0) for patients with an excellent response after 15 months, 47.5 months (95% CI, 44.9-50.1) for patients with an intermediate response, and 17.4 months (95% CI, 13.6-21.2) for patients with a poor response., Conclusions: Among patients with JIA who initiated treatment with etanercept, one-third achieved an excellent response, one-third an intermediate response, and one-third a poor response to therapy. Achievement of an excellent response was associated with low baseline disability scores, DMARDs used before initiating etanercept, and younger age at onset of JIA. Achievement of a poor treatment response was associated with systemic JIA and female sex.

Objective: To evaluate the effectiveness and safety of biological agents in children with enthesitis-related arthritis (ERA)., Methods: All patients with ERA in whom a biological agent was initiated between 1999 and 2010 were selected from the Dutch Arthritis and Biologicals in Children (ABC) register. In this ongoing multicenter observational register, data on the course of the disease and medication use are retrieved prospectively at the start of the biological agent, after 3 months, and yearly thereafter. Inactive disease was assessed in accordance with the Wallace criteria., Results: Twenty-two patients with ERA started taking 1 or more biological agents: 20 took etanercept, 2 took adalimumab (1 switched from etanercept to adalimumab), and 2 took infliximab (1 switched from etanercept to infliximab). Characteristics: 77% were male, 77% had enthesitis, 68% were HLA-B27-positive. The median age of onset was 10.4 (IQR 9.4-12.0) years; median followup from the start of the biological agent was 1.2 (IQR 0.5-2.4) years. Intention-to-treat analysis shows that inactive disease was achieved in 7 of 22 patients (32%) after 3 months, 5 of 13 patients (38%) after 15 months, and 5 of 8 patients (63%) after 27 months of treatment. Two patients discontinued etanercept because of ineffectiveness, and switched to adalimumab (inactive disease achieved) or infliximab (decline in joints with arthritis after 3 months of treatment). One patient discontinued etanercept because of remission, but had flare and restarted treatment, with good clinical response. No serious adverse events occurred., Conclusion: Tumor necrosis factor (TNF)-blocking agents seem effective and safe for patients with ERA that was previously unresponsive to 1 or more DMARD. However, a sustained disease-free state could not be achieved, and none discontinued TNF-blocking agents successfully.

Objective: To analyse and report the costs and effects of etanercept therapy in patients with JIA., Methods: Forty-nine JIA patients were evaluated by means of the JIA core set at the start of etanercept and after 3, 15 and 27 months of therapy. At the same time-points, parents of the patients were asked to complete the Health Utility Index Mark 3 (HUI3). Direct medical costs were collected for 1 year before and 27 months after the start of etanercept and compared with gain in utility., Results: Mean total direct medical costs after the start of etanercept were on average 12 478 euros per patient-year compared with 3720 euros before start. The cost analysis showed that three-quarters of total direct medical costs were from etanercept itself. Other direct medical costs, such as costs concerning hospitalization and concomitant medication, decreased compared with the costs in the period before start of etanercept. Especially a great reduction of consultations at the outpatient clinic was seen. Utility was 0.53 before start of etanercept, according to the multi-attribute utility function of the HUI3 on a scale from 0 (dead) to 1 (perfect health). After 27 months, utility was 0.78. In accordance, also all JIA core set response variables improved significantly over 27 months of etanercept treatment., Conclusions: Although costs of etanercept therapy are substantial, the gain in utility is even more impressive. Considering that these JIA patients were previously refractory to conventional treatment including MTX, and were at risk of long-time disability and pain, costs are justifiable.

Background: Assessing prescription patterns of asthma medication for children is helpful to optimize prescribing by general practitioners (GPs). The aim was to explore prescription patterns in children with physician-diagnosed asthma and its determinants in general practice., Methods: We used the Second Dutch National Survey of General Practice (DNSGP-2) with children aged 0-17 years registered in 87 general practices. All children with at least one asthma prescription were included (n = 2993). Prescription rates and prescription of continuous (≥3 prescriptions/year) versus intermittent asthma medication were calculated. Data, including several GP characteristics, were analysed using multivariate logistic regression accounting for clustering within practices., Results: During one year, 16% of the children with physician-diagnosed asthma (n = 3562) received no asthma medication. Of the 2993 children with asthma receiving asthma medication (on average 2.9 prescriptions/year), 61% received one or two prescriptions, 39% received three or more. Continuous medication with a bronchodilator and/or a corticosteroid was prescribed in 22% of these children. One out of 5 children receiving continuous medication was prescribed a bronchodilator only. In 7.5% of the prescriptions, asthma medications other than bronchodilators or corticosteroids were prescribed. Prescribing asthma medication varied widely between practices, but none of the children and GP determinants had an independent effect on prescribing continuous versus intermittent medication., Conclusion: In general practice, the annual number of asthma prescriptions per child with asthma is relatively low. One in 20 children is prescribed bronchodilators only continuously, indicating room for improvement. Child and GP characteristics cannot be used for targeting educational efforts.

Objectives: To evaluate the effectiveness of tumour necrosis factor (TNF) blockers in juvenile psoriatic arthritis (JPsA)., Methods: The study was a prospective ongoing multicentre, observational study of all Dutch juvenile idiopathic arthritis (JIA) patients using biologicals. The response of arthritis was assessed by American College of Rheumatology (ACR) paediatric response and Wallace inactive disease criteria. The response of psoriatic skin lesions was scored by a 5-point scale., Results: Eighteen JPsA patients (72% female, median age onset 11.1 (range 3.3-14.6) years, 50% psoriatic skin lesions, 39% nail pitting, 22% dactylitis) were studied. The median follow-up time since starting anti-TNFα was 26 (range 3-62) months. Seventeen patients started on etanercept and one started on adalimumab. After 3 months of treatment 83% of the patients achieved ACR30 response, increasing to 100% after 15 months. Inactive disease reached in 67% after 39 months. There was no discontinuation because of inefficacy. Six patients discontinued treatment after a good clinical response. However, five patients flared and restarted treatment, all with a good response. During treatment four patients (two JPsA and two JIA patients with other subtypes) developed de novo psoriasis. In four of the nine patients the pre-existing psoriatic skin lesions improved., Conclusion: Anti-TNFα therapy in JPsA seems effective in treating arthritis. However, in most patients the arthritis flared up after treatment discontinuation, emphasising the need to investigate optimal therapy duration. The psoriatic skin lesions did not respond well and four patients developed de novo psoriasis.

This study aimed to determine disease activity patterns in juvenile systemic lupus erythematosus (jSLE) and its relation to early treatment. All jSLE patients who visited the outpatient departments of three Dutch university hospitals for at least 6 months were included. Data were retrospectively collected from each patient visit and hospitalization. Patient characteristics, clinical and laboratory findings categorized in organ systems, flare rate, medication use and disease course were analysed. Included were 35 patients (female 77%; White 47%) with a total follow-up of 142 years. Median age at diagnosis was 12.8 years. Flare rate was 0.45/ patient-year. An organ system not earlier involved was affected in 34% of flares. Identifiable disease activity patterns were: chronic active (49%), relapse remitting (14%) and long quiescence (37%), with no significant difference in organ involvement at diagnosis. Positive anti-Sm and non-White ethnicity were significantly associated with a chronic active pattern. In 14 patients with severe symptoms at diagnosis, treatment with intravenous cyclophosphamide and/or biologics and/or intravenous methylprednisone in the first 6 months resulted in a long quiescence pattern in seven patients. In conclusion, distinct disease activity patterns are identifiable in children. Suppression of disease with early aggressive treatment may decrease the rate of progression.

Background: The differential diagnosis of children with acute non-traumatic hip pathology varies from quite harmless conditions such as transient synovitis of the hip to more severe problems like Perthes' disease, slipped capital femoral epiphysis (SCFE) and life-threatening conditions such as septic arthritis of the hip., Objective: To provide population-based data on symptom presentation and incidence rates of non-traumatic acute hip pathology in family practice., Methods: We analysed data from a large national survey of family practice (104 practices), which was carried out by the Netherlands Institute for Health Services Research (NIVEL) in 2001. We included all children aged 0-14 years. Incidence rates were calculated by dividing the total number of cases (numerator) by the average study population at risk (denominator)., Results: Our study population consisted of 73 954 children aged 0-14 years, yielding 68 202 person-years. These children presented with 101 episodes of acute non-traumatic hip pathology. The presenting feature in 81.5% of the children was pain, in 8.6% limping and 9.9% presented with both symptoms. Only 27% of the participating family practitioners (FPs) reported whether the child had a fever. The incidence rate for all acute non-traumatic hip pathology was 148.1 per 100 000 person-years, and for transient synovitis, this was 76.2 per 100 000 person-years., Conclusion: In family practice, most children with acute non-traumatic hip pathology present with pain as the initial symptom. FPs need to be more aware that fever is the main distinguishing factor between a harmless condition and a life-threatening condition. Transient synovitis is the diagnosis with the highest incidence rate.

Objective: To evaluate response in patients with juvenile idiopathic arthritis (JIA) who failed to meet response criteria after 3 months of etanercept treatment., Methods: This was a prospective ongoing multicenter observational study of all Dutch patients with JIA using etanercept. Response according to American College of Rheumatology Pediatric 30 criteria was assessed at study start and at 3 and 15 months., Results: In total we studied 179 patients of median age 5.8 years at disease onset; 70% were female. Thirty-four patients did not respond after 3 months, of which 20 continued etanercept and 11 achieved response thereafter., Conclusion: The delayed clinically relevant response in a substantial proportion of patients who initially did not respond justifies the consideration of continuing therapy to at least 6 months.

Objective: Juvenile idiopathic arthritis (JIA) is a heterogeneous disease involving chronic arthritis. The clinical course is characterized by a fluctuating pattern of active and inactive disease. We have described in detail the clinical course in different JIA subtypes during the first 2 years after diagnosis and studied its relationship to disease activity in the following years., Methods: Detailed clinical data on different parameters describing the disease activity in sequential time periods covering the first 2 years after diagnosis were retrieved from the charts of 311 patients with JIA and compared between subtypes. In a cohort of 146 patients, the relation of these different clinical variables to the course of disease in the following 3 years was evaluated., Results: The percentage of time with active disease in the first 2 years differed significantly between subtypes. In all subtypes, a broad spectrum of activity was observed. The time with active disease in the first 2 years was the most significant factor associated with the duration of active disease in the following years., Conclusion: Different percentages of time with active disease have been observed between JIA subtypes in the first 2 years. The cumulative duration of activity varied widely within each subtype. Regarding the prognosis of the individual patient, the clinical course in the first 2 years appears to be predictive of the clinical course in the following years. Patients that have less time with active disease in the first 2 years are not likely to develop an unremitting clinical course later on.

Objective: To evaluate changes in health-related quality of life (HRQoL) in patients with refractory juvenile idiopathic arthritis (JIA) who are being treated with etanercept., Methods: 53 patients with JIA from seven Dutch centres were included. HRQoL was measured by the Childhood Health Assessment Questionnaire (CHAQ), Child Health Questionnaire (CHQ) and Health Utilities Index mark 3 (HUI3) at the start and after 3, 15 and 27 months of treatment. At the same time points the following JIA disease activity variables were collected; physician's global assessment through the visual analogue scale (VAS), number of active and limited joints and erythrocyte sedimentation rate. A statistical method linear mixed models was used to assess outcomes over time., Results: During etanercept treatment both disease-specific and generic HRQoL outcomes improved dramatically. Significant improvements were shown after 3 months and these improvements continued at least up to 27 months of treatment. The disease-specific CHAQ, including VAS pain and wellbeing, showed a significant improvement in all domains. The generic health-profile measure CHQ improved for all the health concepts except for "family cohesion", which was normal. The generic preference-based HUI3 showed impairment and, subsequently, significant improvement in the more specific domains ("pain", "ambulatory", "dexterity"). In accordance disease activity variables also improved significantly over time., Conclusion: This study shows that the HRQoL of patients with refractory JIA can be substantially improved by the use of etanercept for all aspects impaired by JIA. Information on HRQoL is crucial to understand the complete impact of etanercept treatment on patients with JIA and their families.

Objective: To investigate changes in the craniofacial skeleton in relation to the changes in condylar alterations that occur during long-term follow-up in patients with juvenile idiopathic arthritis., Materials and Methods: Temporomandibular joint (TMJ) involvement is defined as a condylar alteration that is observed on the orthopantomogram. Lateral cephalograms were used to determine linear and angular measurements., Results: Seventy of 97 patients from the initial study cohort were included, with a mean follow-up of 68 months. The overall prevalence of condylar alterations and posterior rotation of the mandible decreased; however, the prevalence of retrognathia remained the same. Patients showed improvement in the degree of retrognathia and posterior rotation (40% ANB, 51% OP-SN, and 44% GO-GN-SN). Improvement in the degree of retrognathia was seen more often in patients with improved condylar alterations than in patients with persistent alterations and in those without alterations (50%, 33%, and 28%, respectively). The degree of posterior rotation improved almost equally in patients without TMJ involvement and in patients with improved condylar alterations (57% and 50% by OP-SN, and 67% and 38% GO-GN-SN, respectively) and did not improve in patients with stable persistent alterations., Conclusion: Both condylar and craniofacial alterations can improve in patients with juvenile idiopathic arthritis.

Background: Molluscum contagiosum is a common skin infection, caused by a pox virus. The infection will usually resolve within months in people with a normal immune system. Many treatments have been used for molluscum contagiosum but a clear evidence base supporting them is lacking.This is an updated version of the original Cochrane Review published in Issue 2, 2006., Objectives: To assess the effects of management strategies (including waiting for natural resolution) for cutaneous, non-genital molluscum contagiosum in otherwise healthy people., Search Strategy: In June 2009 we updated our searches of the Cochrane Skin Group Specialised Register, the Cochrane Central Register of Controlled Trials (CENTRAL) in The Cochrane Library (Issue 2, 2009), MEDLINE, EMBASE, and LILACS. We also searched ongoing trials registers, reference lists, and contacted pharmaceutical companies and experts in the field., Selection Criteria: We investigated randomised controlled trials (RCTs) for the treatment of molluscum contagiosum. We excluded trials on sexually transmitted molluscum contagiosum and in people with lowered immunity (including those with HIV infection)., Data Collection and Analysis: Two authors independently selected studies, assessed methodological quality, and extracted data from selected studies., Main Results: Eleven studies, with a total number of 495 participants, examined the effects of topical (9 studies), systemic, and homoeopathic interventions (1 study each). Limited evidence was found for the efficacy of sodium nitrite co-applied with salicylic acid compared to salicylic acid alone (risk ratio (RR) 3.50, 95% confidence interval (CI) 1.23 to 9.92); for Australian lemon myrtle oil compared to its vehicle, olive oil (RR 17.88, 95% CI 1.13 to 282.72); and for benzoyl peroxide cream compared to tretinoin (RR 2.20, 95% CI 1.01 to 4.79). No statistically significant differences were found for 10 other comparisons, most of which addressed 2 topical treatments.Study limitations included no blinding (four studies), many dropouts (three studies), and no intention-to-treat analysis; small study sizes may have led to important differences being missed. None of the evaluated treatment options were associated with serious adverse effects., Authors' Conclusions: No single intervention has been shown to be convincingly effective in the treatment of molluscum contagiosum. The update identified six new studies, most of them reporting on interventions not included in the original version. However, the conclusions of the review did not change.

Background: Pulled elbow (nursemaid's elbow) is a common injury in young children. It results from a sudden pull on the arm, usually by an adult or taller person, which pulls the radius through the annular ligament, resulting in subluxation (partial dislocation) of the radial head. The child experiences sudden acute pain and loss of function in the affected arm. Pulled elbow is usually treated by manual reduction of the subluxed radial head. Various manoeuvres can be applied. Most textbooks recommend supination of the forearm, as opposed to pronation and other approaches. It is unclear which manoeuvre is most successful., Objectives: The objective of this review is to compare the effectiveness and painfulness of the different methods used to manipulate pulled elbow in young children., Search Strategy: We searched the Cochrane Bone, Joint and Muscle Trauma Group Specialised Register, the Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE, CINAHL, LILACS, PEDro, clinical trial registers and reference lists of articles. Date of last search: January 2009., Selection Criteria: Any randomised or quasi-randomised controlled clinical trials evaluating manipulative interventions for pulled elbow were included. Our primary outcome was failure at the first attempt, necessitating further treatment., Data Collection and Analysis: Two review authors independently evaluated trials for inclusion and, for the included trials, independently assessed the risk of bias and extracted data., Main Results: Three trials with 313 participants, all younger than seven years old, were included. All three trials compared pronation versus supination. The methodological quality of all three trials was low because of incomplete reporting and high risk of bias resulting from lack of assessor blinding. Pronation resulted in statistically significantly less failure than supination (risk ratio 0.53, 95% confidence interval 0.32 to 0.87). Pain perception was reported by two trials but data were unavailable for pooling. Both studies concluded that the pronation technique was less painful than the supination technique., Authors' Conclusions: There is limited evidence from three small low-quality trials that the pronation method might be more effective and less painful than the supination method for manipulating pulled elbow in young children. However, only a small difference in effectiveness was found. We recommend that a high quality randomised trial be performed to strengthen the evidence.

Objective: To develop a reliable and user-friendly digital Childhood HAQ (CHAQ) to facilitate systematic monitoring of disease activity at the outpatient clinic in juvenile idiopathic arthritis (JIA) patients., Methods: The digital CHAQ was tested with patients who visited the outpatient paediatric rheumatology clinic of the Erasmus MC Sophia Children's Hospital. These patients completed in a randomized order the paper form and digital CHAQ while being observed. Validity was tested by comparing outcomes with the paper form CHAQ. User-friendliness was evaluated through a short questionnaire., Results: A digital CHAQ was developed and revised several times according to our observations. Outcome is automatically calculated and can be printed. Fifty-one patients completed both the digital and paper form CHAQ. Correlation coefficient between both outcomes of the CHAQ Disability Index was 0.974. No statistically significantly differences in median outcome were found in visual analogue scale (VAS) pain (25.6 vs 25.9 mm) and VAS well-being (20.1 vs 19.5 mm). Although the mean time (5.06 min) to complete the digital CHAQ was significantly longer than the mean time (3.75 min) to complete the paper form, the majority of patients (75%) preferred the digital version. User-friendliness received maximum positive score., Conclusion: We developed a reliable and user-friendly digital CHAQ, which can be easily and systematically completed during routine clinic visits. Such digitalization of questionnaires can be applied in any field to make systematic monitoring of disease activity in daily practice possible.

Purpose: The obesity epidemic in children is spreading at alarming rates. Because musculoskeletal problems can influence physical activity, we compared the frequency of musculoskeletal problems in overweight and obese children with that in normal-weight children., Methods: We performed a cross-sectional database and face-to-face interview study that included 2,459 children aged 2 to 17 years from Dutch family practices. We collected data on self-reported height and weight (body mass index), self-reported musculoskeletal problems in the 2 weeks before the interview, number of family physician consultations for musculoskeletal problems in 1 year, and age (2 age-groups were analyzed: 2 to 11 years and 12 to 17 years, because of the proxy interview in the youngest age-group). We calculated the odds ratio (OR) and 95% confidence interval (CI) for musculoskeletal problems in overweight and obese children, compared with normal-weight children., Results: Overweight and obese children in both age-groups (2 to 11 years and 12 to 17 years) reported significantly more musculoskeletal problems (OR = 1.86; 95% CI, 1.18-2.93; and OR = 1.69; 95% CI, 1.08-2.65, respectively) than normal-weight children. The total group of children who were overweight or obese reported more lower extremity problems than did the normal-weight children (OR = 1.62; 95% CI, 1.09-2.41); furthermore, they reported more ankle and foot problems than children who were of normal weight (OR = 1.92; 95% CI, 1.15-3.20). Overweight and obese children aged 12 to 17 years consulted their family physicians more often with lower extremity problems than did the normal-weight children (OR = 1.92; 95% CI, 1.05-3.51)., Conclusion: This study shows that overweight and obese children more frequently experience musculoskeletal problems than do normal-weight children.

Background: In recent decades, studies on the management of common foot problems in children have suggested that in many cases, there is no indication for treatment. It is not known whether these studies have changed daily practice., Objective: Our aim was to establish and compare incidence and referral rates for foot problems in children in 1987 and 2001., Methods: A comparison was made of two large consecutive surveys in Dutch general practice performed in 1987 (86 577 children aged 0-17 years) and 2001 (87 952 children aged 0-17 years), which were carried out by The Netherlands Institute for Health Services Research. Both surveys included a representative sample of the Dutch population. Incidence and referral rates were calculated and, data were stratified for age group and gender., Results: Compared to 1987, in 2001 the overall incidence rate of foot problems presented to the family physician (FP) decreased substantially from 80.0 [95% confidence interval (CI) 77.0-84.7] to 17.4 (95% CI 16.5-18.3) per 1000 person-years (P < 0.0001). The incidence rate of flat feet decreased from 4.9 (95% CI 4.0-5.9) per 1000 person-years in 1987 to 3.4 (95% CI 3.0-3.8) per 1000 person-years in 2001 (P = 0.001). The distribution of referrals to other primary health care professionals and medical specialists has almost reversed in favour of primary health care professionals., Conclusion: Total incidence rate of musculoskeletal foot problems seen by the FP has decreased substantially, between 1987 and 2001.