Search

Objective.Around one-third of patients with juvenile idiopathic arthritis (JIA) fail to respond to first-line methotrexate (MTX) or anti-tumor necrosis factor (TNF) therapy, with even fewer achieving ≥ American College of Rheumatology Pediatric 70% criteria for response (ACRpedi70), though individual responses cannot yet be accurately predicted. Because change in serum S100-protein myeloid-related protein complex 8/14 (MRP8/14) is associated with therapeutic response, we tested granulocyte-specific S100-protein S100A12 as a potential biomarker for treatment response.Methods.S100A12 serum concentration was determined by ELISA in patients treated with MTX (n = 75) and anti-TNF (n = 88) at baseline and followup. Treatment response (≥ ACRpedi50 score), achievement of inactive disease, and improvement in Juvenile Arthritis Disease Activity Score (JADAS)-10 score were recorded.Results.Baseline S100A12 concentration was measured in patients treated with anti-TNF [etanercept n = 81, adalimumab n = 7; median 200, interquartile range (IQR) 133–440 ng/ml] and MTX (median 220, IQR 100–440 ng/ml). Of the patients in the anti-TNF therapy group, 74 (84%) were also receiving MTX. Responders to MTX (n = 57/75) and anti-TNF (n = 66/88) therapy had higher baseline S100A12 concentration compared to nonresponders: median 240 (IQR 125–615) ng/ml versus 150 (IQR 87–233) ng/ml, p = 0.021 for MTX, and median 308 (IQR 150–624) ng/ml versus 151 (IQR 83–201) ng/ml, p = 0.002, for anti-TNF therapy. Followup S100A12 could be measured in 44/75 MTX-treated patients (34/44 responders) and 39/88 anti-TNF-treated patients (26/39 responders). Responders had significantly reduced S100A12 concentration (MTX: p = 0.031, anti-TNF: p < 0.001) at followup versus baseline. Baseline serum S100A12 in both univariate and multivariate regression models for anti-TNF therapy and univariate analysis alone for MTX therapy was significantly associated with change in JADAS-10.Conclusion.Responders to MTX or anti-TNF treatment can be identified by higher pretreatment S100A12 serum concentration levels.

Over the past decades, the intestinal microbiota has increasingly gained attention in studies addressing the pathophysiology of (pediatric) autoimmune diseases, including inflammatory joint diseases, inflammatory bowel disease (IBD), and type 1 diabetes. In this study, we have analyzed the composition of gut microbiota of newly diagnosed juvenile idiopathic arthritis (JIA) patients, prior to initiation of disease-modifying antirheumatic drugs (DMARDs). Fecal microbiota profiles of 8 JIA patients (median age: 11.1 years, 6 girls) were compared with 22 healthy age-matched controls using IS-pro, a 16S-23S interspacer (IS) region-based, eubacterial molecular detection technique. By partial least squares discriminant analysis (PLS-DA), microbiota profiles of JIA and controls could significantly be discriminated based on a limited set of species belonging to the phylum Bacteroidetes ( Fig. 2 ), but not within other phyla, with a sensitivity of 88%, specificity of 73% ( Fig. 3 ), and area under the curve (AUC) 0.87 (95% CI: 0.73–0.87). These discriminative species have been considered to be part of the microbial core in healthy children. Conclusion Our findings add to the increasing notion that the gut microbiota may be involved in the pathophysiology of JIA. Species involved in the discrimination between JIA and controls are members of the microbial core in the healthy state. Expanding knowledge on JIA-specific microbial signatures and host interactions may open avenues to explore options to develop individualized, microbiota-based preventive, and therapeutic interventions in JIA.

Background Genuine uncertainty on superiority of one intervention over the other is called equipoise. Physician-investigators in randomized controlled trials (RCT) need equipoise at least in studies with more than minimal risks. Ideally, this equipoise is also present in patient-participants. In pediatrics, data on equipoise are lacking. We hypothesize that 1) lack of equipoise at enrolment among parents may reduce recruitment; 2) lack of equipoise during participation may reduce retention in patients assigned to a less favoured treatment-strategy. Methods We compared preferences of parents/patients at enrolment, documented by a questionnaire (phase 1), with preferences developed during follow-up by an interview-study (phase 2) to investigate equipoise of child-participants and parents in the BeSt-for-Kids-study (NTR 1574). This trial in new-onset Juvenile Idiopathic Arthritis-patients consists of three strategies. One strategy comprises initial treatment with a biological disease-modifying-antirheumatic-drug (DMARD), currently not standard-of-care. Semi-structured interviews were conducted with 23 parents and 7 patients, median 11 months after enrolment. Results Initially most parents and children were not in equipoise. Parents/patients who refused participation, regularly declined due to specific preferences. Many participating families preferred the biological-first-strategy. They participated to have a chance for this initial treatment, and would even consider stopping trial-participation when not randomized for it. Their conviction of superiority of the biological-first strategy was based on knowledge from internet and close relations. According to four parents, the physician-investigator preferred the biological-first-strategy, but the majority (n = 19) stated that she had no preferred strategy. In phase 2, preferences tended to change to the treatment actually received. Conclusions Lack of equipoise during enrolment did not reduce study recruitment, mainly due to the fact that preferred treatment was only available within the study. Still, when developing a trial it is important to evaluate whether the physicians’ research question is in line with preferences of the patient-group. By exploring so-called ‘informed patient-group’-equipoise, successful recruitment may be enhanced and bias avoided. In our study, lack of equipoise during trial-participation did not reduce retention in those assigned to a less favoured option. We observed a change for preference towards treatment actually received, possibly explained by comparable outcomes in all three arms. Electronic supplementary material The online version of this article (10.1186/s12910-018-0336-8) contains supplementary material, which is available to authorized users.

This is a protocol for a Cochrane Review (Intervention). The objectives are as follows: The aim of this review is to assess the benefit and safety of TNF-α inhibitors in JIA.

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.

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.

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.

Item does not contain fulltext 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. 01 april 2013

Item does not contain fulltext 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-naive 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. 01 september 2013

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.

Item does not contain fulltext 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. 01 mei 2013

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. Plain Language Summary There is not enough evidence to show that any particular treatment is effective for treating molluscum infection. Molluscum contagiosum, in healthy people, is a self limiting, relatively harmless viral skin infection. It affects mainly children and adolescents. It occurs worldwide but is much more frequent in certain geographic areas with warm climates. Molluscum contagiosum usually presents as single or multiple pimples filled with fluid. People may seek treatment for social and aesthetic reasons and because of concerns about spreading the disease to others. Treatment is intended to speed up the healing process. Eleven studies with 495 patients were included in this review. This review found that many common treatments for molluscum, such as physical destruction, have not been adequately evaluated. Several of the treatments that we studied are not part of daily practice. Limitations of several of these studies were: small numbers of patients, the investigators were not blinded, and patients who did not complete the study (which were numerous in some studies) were not included in the analysis. None of the evaluated treatment options were associated with serious adverse effects. Since most lesions will resolve within months, molluscum contagiosum can be left to heal naturally unless better evidence for the superiority of other treatment options emerges.

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.

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. Plain Language Summary Different methods of manipulation for reducing pulled elbow in young children Pulled elbow is a dislocation of the elbow joint in a young child which is usually caused by an adult, or taller person, suddenly pulling or tugging on the child's arm when it is straight; or when a child pulls away from an adult impulsively. The child immediately complains of pain and cannot use their arm. Treatment usually consists of manipulating the arm to get the bones of the elbow back into their correct position. It is usually treated by manual intervention. In the typical manoeuvre, called supination, the forearm is twisted or rotated outwards (palm of child's hand faces upwards), sometimes followed by bending of the elbow. While this has become standard practice, it is not always successful. Other methods, particularly the use of pronation, where the forearm is twisted or rotated inwards (palm of child's hand faces downwards), have also been used. These methods are generally safe, although bruising can occur and they can be painful. Evidence from three small, low quality trials involving a total of 313 participants indicates that the pronation method (with the hand downward) is more successful in repositioning and less painful for children with a pulled elbow.

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.

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. JAMA. 2011;306(21):2340-2347 Published online November 6, 2011. doi:10.1001/jama.2011.1671

PURPOSE The obesity epidemic in children is spreading at alarming rates. Because musculoskeletal problems can infl uence 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 prac- tices. 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% confi dence interval (CI) for musculoskeletal problems in over- weight 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 signifi cantly more musculoskeletal problems (OR = 1.86; 95% CI, 1.18-2.93; and OR = 1.69; 95% CI, 1.08-2.65, respectively) than nor- mal-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 fre- quently experience musculoskeletal problems than do normal-weight children.

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.

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.

Objective. Temporomandibular joint (TMJ) involvement is a frequent feature in cross-sectional prevalence studies among patients with juvenile idiopathic arthritis (JIA). In this followup study, patients were reviewed after 5 years to study the course of TMJ involvement in relation to disease characteristics.Methods. Children with JIA from a previous study on TMJ involvement were included. A rheumatologic evaluation including the 6 parameters of the JIA core set and an orthodontic evaluation including an orthopantomogram (OPT) were performed. OPTs were scored according to Rohlin's grading system (grades 0-5).Results. The overall prevalence of patients with condylar alterations decreased from 49% to 40%. Improvement of the alterations was seen in 69% of the initially affected condyles, and consequently improvement was seen in 83% of the initially affected patients. Normalization of the alterations was seen in 67% of the improved condyles, and consequently in 44% of the patients. This proves that the condyle has a regenerative capacity. Improvement was related to low disease activity and a less extensive therapeutic regimen.Conclusion. In patients with JIA, condylar alterations can improve and even regenerate. Condylar improvement is associated with a low disease activity.

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 onethird 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.

Item does not contain fulltext 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.

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

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. 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. 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

BackgroundTreatment of juvenile idiopathic arthritis (JIA) has changed dramatically since the introduction of biological agents in 1999.ObjectiveTo evaluate trends in prescription patterns of biological agents and the subsequent outcome of JIA.MethodsThe 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.Results335 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.ConclusionsBiological 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.

Background The increasing proportion of skin diseases encountered in general practice represents a substantial part of morbidity in children. Only limited information is available about the frequency of specific skin diseases. We aimed to compare incidence rates of skin diseases in children in general practice between 1987 and 2001. Methods We used data on all children aged 0–17 years derived from two consecutive surveys performed in Dutch general practice in 1987 and 2001. Both surveys concerned a longitudinal registration of GP consultations over 12 months. Each disease episode was coded according to the International Classification of Primary Care. Incidence rates of separate skin diseases were calculated by dividing all new episodes for each distinct ICPC code by the average study population at risk. Data were stratified for socio-demographic characteristics. Results The incidence rate of all skin diseases combined in general practice decreased between 1987 and 2001. Among infants the incidence rate increased. Girls presented more skin diseases to the GP. In the southern part of the Netherlands children consulted their GP more often for skin diseases compared to the northern part. Children of non-Western immigrants presented relatively more skin diseases to the GP. In general practice incidence rates of specific skin diseases such as impetigo, dermatophytosis and atopic dermatitis increased in 2001, whereas warts, contact dermatitis and skin injuries decreased. Conclusion The overall incidence rate of all skin diseases combined in general practice decreased whereas the incidence rates of bacterial, mycotic and atopic skin diseases increased.

Instruments for measuring pain-related problems in adolescents with chronic pain are sparse, especially those based on the personal experiences of these adolescents. This study aimed to develop and test such an instrument, the pain-related problem list for adolescents (PPL). A sample of 129 adolescents with chronic pain without documented physiological etiology completed the 57-item problem list, which was based on interviews with a similar group of adolescents with chronic pain. Principal components analysis yielded four domains: problems related to (1) concentration; (2) mobility; (3) adaptability; and (4) mood. The questionnaire was shortened to 18 items and has good reliability (total alpha = 0.82; concentration alpha = 0.86; mobility alpha = 0.77; adaptability alpha = 0.71; and mood alpha = 0.78); the validity also proved to be adequate, especially in the general population sample. The PPL provides a tool to assess the impact of chronic pain in adolescents. Future research should focus on further validation of the PPL in a large clinical population and establishing its test-retest reliability.

OBJECTIVES: To examine the presentation and pattern of childhood morbidity in general practice compared with 14 years ago.METHODS: We used data of all children aged 0-17 years from two cross-sectional surveys performed in 1987 and 2001 in general practice in the Netherlands. The total number of children in the practices participating in these surveys were 86,577 children in 1987 and 82,053 children in 2001. First of all, we compared consultation rates of children in general practice. Secondly, childhood morbidity was assessed by episodes of disease, coded according to the International Classification of Primary Care (ICPC). We compared childhood morbidity in 1987 and 2001 by assessing the distribution of episodes among ICPC chapters stratified by ethnicity, and by comparing incidence rates of most frequently presented diseases.RESULTS: Childhood consultation rates have decreased from 2.7 visits a year per child in 1987 to 2.1 in 2001. The distribution of episodes among ICPC chapters had also changed. Respiratory problems are still the most frequently presented health problem in children but the proportion has decreased from 25.5% in 1987 to 23.3% in 2001. Skin problems were presented more often (23.0% in 2001 versus 17.8 in 1987), and Western children more often presented with skin problems than with respiratory problems in 2001. Incidence rates of most respiratory diseases have decreased and specific skin diseases (dermatomycosis, impetigo and eczema) were diagnosed more often.CONCLUSION: In the Netherlands, childhood morbidity has changed. Skin diseases have become more important in general practice and respiratory problems are declining.

There is little evidence that influenza vaccination reduces asthma exacerbations. We determined whether influenza vaccination is more effective than placebo in 6-18-year-old children with asthma. We performed a randomized, double-blind, placebo-controlled trial. Parenteral vaccination with inactivated influenza vaccine or placebo took place approximately November 1, and children were followed until April 1 of the next year. Airway symptoms were reported in a diary. When symptom scores reached a predefined level, a pharyngeal swab was taken. Primary outcome was the number of asthma exacerbations associated with virologically proven influenza infection. Three hundred forty-nine children were assigned placebo, and 347 were assigned vaccine. Pharyngeal swabs positive for influenza were related to 42 asthma exacerbations, 24 in the vaccine group and 18 in the placebo group, a difference of 33% favoring placebo (31% after adjustment for confounders; 95% confidence interval, -34% to 161%). Influenza-related asthma exacerbations were of similar severity in both groups; they lasted 3.1 days shorter in the vaccine group (95% confidence interval, -6.2 to 0.002 days, p = 0.06). We conclude that influenza vaccination did not result in a significant reduction of the number, severity, or duration of asthma exacerbations caused by influenza. Additional studies are warranted to justify routine influenza vaccination of children with asthma.

Doel Impetigo is de meest voorkomende huidinfectie bij kinderen. Wij toetsten de hypothese dat fusidinezuur het behandeleffect van alleen desinfectie met povidonjood niet verbetert.

Objective: Many juveniles with chronic pain of no known organic cause recover. Because adolescents whose pain persists may have chronic pain as adults, a subsample of 42 adolescents from a prevalence study in which continuation of their pain was observed throughout the study period was investigated quantitatively and qualitatively. All mothers (n = 42) completed a questionnaire on the impact of the adolescent's pain on the family. The authors tested the hypothesis that pain parameters, pain-related quality of life, and impact of pain on the family would deteriorate over time. Design: Three-year follow-up questionnaires, diaries, and interviews were used. Setting: The study was conducted in the general population in the Rotterdam area. Participants: Adolescents (aged 12-18 years) who indicated chronic pain in our previous prevalence study and in a diary and questionnaire each year of the 3-year follow-up were included in the study. Results: The most prevalent pains were limb pain and headache. The pain intensity was mild (33 mm on a visual analog scale), very frequent (72% of all diary entries), and associated with relatively poor functional status and poor psychological and somatic functioning. The pain parameters, pain-related quality of life, and impact of pain on the family (i.e., restrictions in social life and problems in dealing with the stress of the adolescent's pain) remained surprisingly stable across the assessments. The interviews showed that pain had become part of the daily life of several adolescents, who structured their activities and sleeping hours to prevent aggravation of pain. In particular, adolescents with headache reported problems with cognitive activities, whereas those with limb pain and back pain reported problems with physical activities. Conclusions: For adolescents with persistent pain with no known organic cause, intensity and frequency of pain, quality of life, and impact of pain on the family did not change. Generally, they seemed to cope quite well with their pain. In view of these results, further studies should involve follow-up of adolescents with persistent pain into adulthood to establish the determinants of their pain and to find out whether they maintain their adaptive ways of living with their pain.

The utilization of health care services in children and adolescents with chronic benign pain was studied in a Dutch population sample of 254 chronic pain sufferers aged 0-18 years. Children and adolescents who had reported chronic pain (continuous or recurrent pain >3 months) in our previous prevalence study were asked to keep a 3-week diary on their pain and to fill out questionnaires on background factors, health care use and the impact of pain. Parent ratings were used for children aged 0-11 years, self-report was used in adolescents (12-18 years). In a 3-month period, in 53.4% of the cases medication was used for pain, and general practitioners and specialists were consulted for pain in 31.1% and 13.9% of subjects, respectively. Physiotherapists, psychologists and alternative health providers were visited by 11.5, 2.8, and 4.0%, respectively. In the preceding year, 6.4% had been hospitalized due to pain. The most important factors linked to utilizing medical services were gender, various pain characteristics, school absenteeism and disability. Although consulters reported to be less physically fit and less satisfied with health, their parents were better adapted to the pain, by talking and sharing, mutual support, normalization of the child and heightened self-esteem, than non-consulters. Prospective studies are needed to test causality of coping on care-seeking behavior.

Objective: The goal of this study was to assess physician consultation and use of medication in Dutch children and adolescents (0-18 years old) having chronic pain in relation to sociodemographic factors and pain characteristics. Design: This was a population-based cross-sectional survey. A questionnaire was either mailed to the participants' parents or distributed at school, and it was filled out by the parents (for children aged 0-7 years) or by the participant (for children and adolescents aged 8-18 years). Setting: The study was conducted in the Rotterdam area. Patients: Participants included a random sample of 1,300 children aged 0 to 3 years taken from the register of population. In addition, 41 schools were selected to obtain a representative sample of 5,336 children and adolescents aged 4 to 18 years. Outcome Measures: Reported physician consultation and medication use were assessed. Results: Of the 6,636 children and adolescents surveyed, 5,424 (82%) responded. A total of 1,358 respondents (25%) reported chronic pain. Of these, 57% had consulted a physician and 39% had used medication for the pain. Respondents with earache, more intense pain, and more frequent pain and those attending lower vocational training programs were more likely to consult a physician for the pain than the average respondent. Respondents with earache, sore throat, headache, more intense pain, and multiple pain; children aged 0 to 3 years; and girls were more likely to use medication for the pain. Logistic regression analyses showed that for physician consultation, the most significant predictive factors were the intensity of pain, age, and earache as well as the level of education for respondents aged 12 to 16 years. The use of medication was predicted by earache, headache, limb pain, intensity of pain, and age. Conclusions: Chronic pain is a common complaint in children and adolescents, frequently resulting in consultation of a physician and medication use. Regarding physician consultation, children and adolescents with a lower educational level seem to be a group at risk.

textabstractObjective: To answer the following question: Are children with asthma known to their GP? Methods: Parents of all 464 children, 1-3 years of age and registered with five general practices, received a postal questionnaire asking about asthma symptoms of the child, and past and present asthma medication. Thus, children were classified as having no, mild, moderate or severe asthma. The GPs' records were checked for recorded asthma symptoms, medication and asthma-related diagnoses. The presence of these items was compared with asthma severity. Results: Eighty-seven percent of parents responded to the questionnaire (mean age of children 30.1 months). For all classes of severity, 75% of children with asthma were known to their GP. Although all children with severe asthma were known to their GP, the proportion of asthmatic children known to their GP fell with decreasing severity. Symptoms and medication were recorded more often than asthma-related diagnoses. Conclusions: Most preschool children with asthma are known to their GP. The diagnosis is recorded less often than asthma symptoms and medication.

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 Bucher9s 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.

Item does not contain fulltext 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 alpha, 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 (p740 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

Item does not contain fulltext 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.

Item does not contain fulltext 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-TNFalpha 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-TNFalpha 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.

Summary points Juvenile idiopathic arthritis is the most common cause of chronic arthritis in childhood; a review of 34 epidemiological studies showed that 0.07-4.01 per 1000 children worldwide are affected.w1 It is characterised by joint inflammation that often leads to joint destruction with physical disability and chronic pain that affects daily life.1 During the past decade, increased understanding of the disease has improved treatment, particularly through earlier diagnosis and new treatments that help to prevent long term damage to joints. Earlier this year, the British Society for Paediatric and Adolescent Rheumatology published standards of care for children and young people with juvenile idiopathic arthritis, which outlined the importance of involving different disciplines within healthcare.2 We review recent advances in the diagnosis and management of juvenile idiopathic arthritis, focusing on evidence from randomised controlled trials, cohort studies, systematic reviews, and current guidelines. #### Sources and selection criteria As well as using our personal reference collections, we searched Medline, Embase, and Cochrane Central for clinical studies and reviews using the keywords “juvenile idiopathic arthritis”, “juvenile rheumatoid arthritis”, “juvenile chronic arthritis”, “diagnosis”, “treatment”, “therapy”, “non-steroidal anti-inflammatory drugs”, “corticosteroids”, “disease modifying antirheumatic drugs”, “biologicals”, and “biologics.” We also reviewed guidelines from the British Society …

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.

Achtergrond In de meeste westerse landen wordt geadviseerd kinderen met astma te vaccineren tegen griep. Er is echter weinig bewijs dat griepvaccinatie resulteert in minder astma-exacerbaties. We onderzochten of griepvaccinatie effectiever is dan placebo ter voorkoming van aan influenza gerelateerde astma-exacerbaties bij kinderen met astma in de leeftijd van 6 tot 18 jaar. Methoden We voerden gedurende 2 seizoenen (1999-2000 en 2000-2001) een gerandomiseerd dubbelblind placebogecontroleerd parallelonderzoek uit bij kinderen met astma die in de huisartsenpraktijk werden gerekruteerd. In aanmerking kwamen kinderen van 6 tot 18 jaar die in het voorafgaande jaar medicatie hadden gebruikt in verband met astma. De kinderen werden parenteraal gevaccineerd met geinactiveerd influenzavaccin of placebo. Luchtwegklachten werden bijgehouden in een dagboek. Wanneer de symptoomscore een bepaald tevoren gedefinieerd niveau bereikte, moesten de deelnemers de onderzoeksverpleegkundige bellen. De verpleegkundige bezocht het kind en nam een keelwat af. De primaire uitkomstmaat was het aantal astma-exacerbaties gerelateerd aan een virologisch aangetoonde influenza-infectie. Resultaten In totaal werden 696 kinderen geincludeerd; 347 ontvingen het vaccin en 349 ontvingen placebo. De keelwatten die positief waren voor influenza hadden betrekking op 42 astma-exacerbaties, waarvan er 24 voorkwamen in de groep die gevaccineerd werd en 18 in de placebogroep: een verschil van 33% ten gunste van placebo (31% na correctie voor confounders; 95%-BI –34-161). De ernst van de aan influenza gerelateerde astma-exacerbaties verschilde niet, maar in de vaccingroep duurden de exacerbaties 3,1 dagen korter (95%-BI –6,2-0,002 dagen; p=0,06). Conclusie Griepvaccinatie bij kinderen met astma resulteerde niet in een significante afname van het aantal, de ernst of de duur van de astma-exacerbaties als gevolg van griep. Vertaling voorHuisarts en Wetenschap van het oorspronkelijke Engelstalige artikel ‘Influenza vaccination in children with asthma, randomized double-blind placebo-controlled trial’ dat verscheen in het American Journal of Respiratory and Critical Care Medicine (2004;169:488-93) © American Thoracic Society. Publicatie gebeurt met toestemming van de uitgever.

Doel Impetigo is de meest voorkomende huidinfectie bij kinderen. Wij toetsten de hypothese dat fusidinezuur het behandeleffect van alleen desinfectie met povidonjood niet verbetert. Opzet Gerandomiseerd placebogecontroleerd onderzoek. Alle kinderen werden behandeld met povidonjoodshampoo en gerandomiseerd naar behandeling met fusidinezuurcreme of met placebocreme. Setting Huisartspraktijken in de regio Rotterdam. Deelnemers Honderdvierentachtig kinderen van nul tot twaalf jaar met impetigo werden aangemeld door hun huisarts en bezocht door een onderzoeksverpleegkundige. Honderdzestig kinderen werden gerandomiseerd. Beoordeling vond plaats na een, twee en vier weken. Primaire uitkomsten Klinische en bacteriele genezing na een week. Resultaten Na een week behandeling waren 55% van de kinderen in de fusidinezuurgroep klinisch genezen tegenover 13% in de placebogroep (odds-ratio 12,6; 95%-BI 5,0-31,5; NNT 2,3). Na twee en vier weken waren de verschillen in genezing tussen beide groepen kleiner. In de placebogroep waren meer kinderen therapieontrouw en kregen meer kinderen alsnog een antibioticum voorgeschreven. De placebogroep rapporteerde meer bijwerkingen. In 96% van de positieve kweken werdS. aureus aangetroffen. Geen van de stammen was resistent voor fusidinezuur. Conclusies Fusidinezuur bleek veel effectiever dan placebo in de behandeling van impetigo. De waarde van povidonjood is twijfelachtig.