Lisette W. A. van Suijlekom-Smit

Pain in children and adolescents: a common experience

&NA; Little is known about the epidemiology of pain in children. We studied the prevalence of pain in Dutch children aged from 0 to 18 years in the open population, and the relationship with age, gender and pain parameters. A random sample of 1300 children aged 0–3 years was taken from the register of population in Rotterdam, The Netherlands. In the Rotterdam area, 27 primary schools and 14 secondary schools were selected to obtain a representative sample of 5336 children aged 4–18 years. Depending on the age of the child, a questionnaire was either mailed to the parents (0–3 years) or distributed at school (4–18 years). Of 6636 children surveyed, 5424 (82%) responded; response rates ranged from 64 to 92%, depending on the subject age and who completed the questionnaire. Of the respondents, 54% had experienced pain within the previous 3 months. Overall, a quarter of the respondents reported chronic pain (recurrent or continuous pain for more than 3 months). The prevalence of chronic pain increased with age, and was significantly higher for girls (P<0.001). In girls, a marked increase occurred in reporting chronic pain between 12 and 14 years of age. The most common types of pain in children were limb pain, headache and abdominal pain. Half of the respondents who had experienced pain reported to have multiple pain, and one‐third of the chronic pain sufferers experienced frequent and intense pain. These multiple pains and severe pains were more often reported by girls (P<0.001). The intensity of pain was higher in the case of chronic pain (P<0.001) and multiple pains (P<0.001), and for chronic pain the intensity was higher for girls (P<0.001). These findings indicate that chronic pain is a common complaint in childhood and adolescence. In particular, the high prevalence of severe chronic pain and multiple pain in girls aged 12 years and over calls for follow‐up investigations documenting the various bio‐psycho‐social factors related to this pain.

Long-term follow-up on effectiveness and safety of etanercept in JIA: the Dutch national register

Objective: We undertook an observational study to obtain a complete overview of the long-term effectiveness and safety of etanercept in patients with different juvenile idiopathic arthritis (JIA) subtypes. Methods: At baseline we collected patient and disease characteristics of all Dutch patients with JIA who started treatment with etanercept. Disease activity was evaluated (at start of the study, after 3 months and then yearly) according to the JIA core set of the American College of Rheumatology paediatric definition for 30, 50 and 70% improvement (ACR Pedi 30, 50 and 70). Use of etanercept and concomitant drugs was monitored. Adverse events were recorded. Results: We included 146 patients with JIA with a median follow-up of 2.5 years per patient (range 0.3–7.3). JIA subtypes represented: 27% systemic, 8% polyarticular rheumatoid factor positive, 38% polyarticular rheumatoid factor negative, 19% oligoarticular extended, 3% enthesitis-related and 5% psoriatica. Most patients (77%) met the criteria of the ACR Pedi 30 in the first 3 months of treatment. For the majority of patients this improvement was sustained; 53 (36%) of all patients met the remission criteria. No other second-line agents were needed in 43 patients. Although patients with systemic JIA responded initially less to etanercept therapy than patients from other subtypes, those who did respond showed equal effectiveness in the long term. Serious adverse events rate was low (0.029 per patient year). Conclusions: Etanercept is effective and safe in JIA, even for a large proportion of the patients with systemic JIA. The greatest improvement occurred in the first 3 months of treatment, and was sustained for a long time in most patients (up to 75 months).

Insights in the use of health care services in chronic benign pain in childhood and adolescence

&NA; 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.

The provisional Paediatric Rheumatology International Trials Organisation/American College of Rheumatology/european League Against Rheumatism Disease activity core set for the evaluation of response to therapy in juvenile dermatomyositis: A prospective validation study†‡

OBJECTIVE To validate a core set of outcome measures for the evaluation of response to treatment in patients with juvenile dermatomyositis (DM). METHODS In 2001, a preliminary consensus-derived core set for evaluating response to therapy in juvenile DM was established. In the present study, the core set was validated through an evidence-based, large-scale data collection that led to the enrollment of 294 patients from 36 countries. Consecutive patients with active disease were assessed at baseline and after 6 months. The validation procedures included assessment of feasibility, responsiveness, discriminant and construct ability, concordance in the evaluation of response to therapy between physicians and parents, redundancy, internal consistency, and ability to predict a therapeutic response. RESULTS The following clinical measures were found to be feasible, and to have good construct validity, discriminative ability, and internal consistency; furthermore, they were not redundant, proved responsive to clinically important changes in disease activity, and were associated strongly with treatment outcome and thus were included in the final core set: 1) physicians global assessment of disease activity, 2) muscle strength, 3) global disease activity measure, 4) parents global assessment of patients well-being, 5) functional ability, and 6) health-related quality of life. CONCLUSION The members of the Paediatric Rheumatology International Trials Organisation, with the endorsement of the American College of Rheumatology and the European League Against Rheumatism, propose a core set of criteria for the evaluation of response to therapy that is scientifically and clinically relevant and statistically validated. The core set will help standardize the conduct and reporting of clinical trials and assist practitioners in deciding whether a child with juvenile DM has responded adequately to therapy.

The natural course of chronic benign pain in childhood and adolescence: A two-year population-based follow-up study

Study objective. To assess the course of chronic benign pain in childhood and adolescence longitudinally.

Factors Associated With Treatment Response to Etanercept in Juvenile Idiopathic Arthritis

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.

The toll-like receptor 4 agonist MRP8/14 protein complex is a sensitive indicator for disease activity and predicts relapses in systemic-onset juvenile idiopathic arthritis

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 physicians 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.

Musculoskeletal Problems in Overweight and Obese Children

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.

Fusidic acid cream in the treatment of impetigo in general practice: double blind randomised placebo controlled trial

Abstract Objective: To test the hypothesis that fusidic acid would not increase the treatment effect of disinfecting with povidone-iodine alone in children with impetigo. Design: Randomised placebo controlled trial. Setting: General practices in Greater Rotterdam. Participants: 184 children aged 0-12 years with impetigo. Main outcome measures: Clinical cure and bacterial cure after one week. Results: After one week of treatment 55% of the patients in the fusidic acid group were clinically cured compared with 13% in the placebo group (odds ratio 12.6, 95% confidence interval 5.0 to 31.5, number needed to treat 2.3). After two weeks and four weeks the differences in cure rates between the two groups had become smaller. More children in the placebo group were non-compliant (12 v 5) and received extra antibiotic treatment (11 v 3), and more children in the placebo group reported adverse effects (19 v 7). Staphylococcus aureus was found in 96% of the positive cultures; no strains were resistant to fusidic acid. Conclusions: Fusidic acid is much more effective than placebo (when both are given in combination with povidone-iodine shampoo) in the treatment of impetigo. Because of the low rate of cure and high rate of adverse events in the placebo group, the value of povidone-iodine in impetigo can be questioned. What is already known on this topic Impetigo is the most common skin infection in children Fusidic acid, which is advocated as topical treatment in several countries, has never been investigated in a placebo controlled study What this study adds In combination with povidone-iodine, treatment with fusidic acid is much more effective than placebo None of the strains of Staphylococcus aureus isolated at baseline showed resistance to fusidic acid The value of treatment with povidone-iodine alone can be questioned

Stability of pain parameters and pain-related quality of life in adolescents with persistent pain: a three-year follow-up.

ObjectiveMany 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 adolescents 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. DesignThree-year follow-up questionnaires, diaries, and interviews were used. SettingThe study was conducted in the general population in the Rotterdam area. ParticipantsAdolescents (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. ResultsThe 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 adolescents 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. ConclusionsFor 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.