Introduction. Advance Access publication 28 July KEY WORDS: Juvenile idiopathic arthritis, Quality of life, Disability, Pain.

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1 Rheumatology 2007;46: Advance Access publication 28 July 2006 doi: /rheumatology/kel218 Health-related quality of life of patients with juvenile idiopathic arthritis coming from 3 different geographic areas. The PRINTO multinational quality of life cohort study R. Gutie rrez-sua rez 1, A. Pistorio 2, A. Cespedes Cruz 1, X. Norambuena 1, B. Flato 3, I. Rumba 4, M. Harjacek 5, S. Nielsen 6, G. Susic 7, D. Mihaylova 8, C. Huemer 9, J. Melo-Gomes 10, B. Andersson-Gare 11, Z. Balogh 12, C. De Cunto 13, R. Vesely 14, K. Pagava 15, A. M. Romicka 16, R. Burgos-Vargas 17, A. Martini 18 and N. Ruperto 1, for the Pediatric Rheumatology International Trials Organisation (PRINTO). Objectives. To compare health-related quality of life (HRQL) and to identify clinical determinants for poor HRQL of patients with juvenile idiopathic arthritis (JIA) coming from three geographic areas. Methods. The HRQL was assessed through the Child Health Questionnaire (CHQ). A total of 30 countries were included grouped in three geographic areas: 16 countries in ; 10 in ; and four in. Potential determinants of poor HRQL included demographic data, physician s and parent s global assessments, measures of joint inflammation, disability as measured by Childhood Health Assessment Questionnaire (CHAQ) and erythrocyte sedimentation rate. Poor HRQL was defined as a CHQ physical summary score (PhS) or psychosocial summary score (PsS) <2 S.D. from that of healthy children. Results. A total of 3167 patients with JIA, younger than 18 yrs, were included in this study. The most affected health concepts (<2 S.D. from healthy children) that differentiate the three geographic areas include physical functioning, bodily pain/ discomfort, global health, general health perception, change in health with respect to the previous year, self-esteem and family cohesion. Determinants for poor HRQL were similar across geographic areas with physical well-being mostly affected by the level of disability while the psychosocial well-being by the intensity of pain. Conclusion. We found that patients with JIA have a significant impairment of their HRQL compared with healthy peers, particularly in the physical domain. Disability and pain are the most important determinants of physical and psychosocial well-being irrespective of the geographic area of origin. KEY WORDS: Juvenile idiopathic arthritis, Quality of life, Disability, Pain. Introduction A complete assessment of children with juvenile idiopathic arthritis (JIA) requires an understanding of the impact of the disease on their daily life. Several studies have evaluated the relationships between the clinical status and the health-related quality of life (HRQL) of children with JIA or other paediatric rheumatic conditions [1 3] both for outcome research and for clinical trials. It is well-known that socio-cultural differences may have a major impact on HRQL and disease outcome [4, 5]. However, perception of HRQL among children with JIA from different countries with diverse socio-cultural features have never been thoroughly assessed. Since most paediatric rheumatic diseases are rare, the collaboration of centres from different countries is crucial and therefore the evaluation of difference in HRQL becomes important if combination of data coming from different 1 IRCCS G Gaslini, Pediatria II, Reumatologia, PRINTO, Genova, Italy, 2 IRCCS G Gaslini, Servizio di Epidemiologia e Biostatistica, Genova, Italy, 3 Rikshospitalet University Hospital, Department of rheumatology, Oslo, Norway, 4 University of Latria, Pediatric Rheumatology, Riga, Latvia, 5 Children s Hospital Zagreb, Department of Pediatrics, Immunology/Rheumatology, Zagreb, Croatia, 6 Juliane Marie Centret, Rigshospitalet, Pediatrisk klinik II, Afsnit 4064, København, Denmark, 7 Institute of Rheumatology, Department of Pediatric Rheumatology, Belgrade, Serbia Montenegro, 8 University Children Hospital, Department of Paediatric Rheumatology, Sofia, Bulgaria, 9 Landeskrankenhaus Bregenz, Bregenz, Austria, 10 Instituto Portugues de Reumatologia, Pediatric Reumatology, Lisbon, Portugal, 11 Ryhov s County Hospital, Department of Child Public Health, Qulturum, Jonkoping, Sweden, 12 National Institute of Rheumatology and Physiotherapy, III General and Pediatric Rheumatol Dpt, Budapest, Hungary, 13 Hospital Italiano de Buenos Aires, Pediatrics, Rheumatology and Immunology Section, Buenos Aires, Argentina, 14 Detska Fakultna Nemocnica, 1st Pediatric Dept, Kosice, Slovakia, 15 Department of Pediatrics and Adolescent Medicine, Tbilisi State Medical University, Tbilisi Hospital #1 and Georgian Scientific-Practical Rheumatology Center, Tbilisi, Georgia, 16 Institute of Rheumatology, Paediatric Clinic, Warsaw, Poland, 17 Rheumatology Department and Faculty of Medicine, Hospital General de Me xico and Universidad Nacional Auto noma de Me xico, Me xico City, México and 18 IRCCS G. Gaslini, Pediatria II, Reumatologia and Dipartimento di Pediatria, Universita` degli Studi, Genova, Italy. Submitted 16 February 2006; revised version accepted 19 May Correspondence to: Nicolino Ruperto, MD, MPH, Paediatric Rheumatology International Trials Organisation (PRINTO), IRCCS G. Gaslini, Universita` di Genova, Pediatria II - Reumatologia, Largo Gaslini, Genova, Italy. nicolaruperto@ospedale-gaslini.ge.it 314 ß The Author Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For Permissions, please journals.permissions@oxfordjournals.org

2 HRQL of life of patients with juvenile idiopathic arthritis 315 geographic areas is planned [5]. Variation in HRQL has been investigated in numerous chronic conditions, both in children and adult populations [4 12] but little information exists on the possible HRQL differences of JIA children living in various geographic areas. Examining HRQL differences is important for two main reasons: first, it provides the base for learning about the cultural specific influence of physical and psychosocial well-being and second, it may help to individualize the HRQL problems that are common to all patients irrespective of the geographic area of origin. The principal aims of the present study was to analyse the Paediatric Rheumatology International Trials Organisation (PRINTO) quality of life cohort database, in order to compare HRQL, and to identify possible demographic and clinical determinants for poor HRQL of children with JIA coming from three geographic areas. Patients and methods Study design, patients and healthy children Patients and healthy children included in this study were part of a cross-sectional sample, which was used to cross-culturally adapt and validate the American English version of the Childhood Health Assessment Questionnaire (CHAQ) [13] and of the Child Health Questionnaire (CHQ) [14] into several languages [15, 16], according to existing guidelines [17]. In brief, the database contains subjects enrolled by the PRINTO members from April 1998 to March 2000, with a diagnosis of JIA by the International League of Associations of Rheumatology (ILAR) criteria [18] and healthy children with an age at the time of the evaluation 18 yrs. In the database, just few patients with psoriatic arthritis and enthesitis-related arthritis are present and therefore they were excluded from further consideration. Healthy children recruited in each study centre were either students in local schools (6 18 yrs old children) or healthy sisters/brothers of JIA patients. A child was defined as healthy after examination by a physician and/or based on the parent s declaration. In each centre, written or verbal informed consent was obtained from a parent or legal guardian and patients, if appropriate for age, according to the requirements of the local ethics committees. Patient selection For the purpose of the present study, 30 countries were analysed and divided in three geographic areas as follows: (i) Western Europe, includes 16 countries: Austria, Belgium, Denmark, Finland, France, Germany, Greece, Italy, The Netherlands, Norway, Portugal, Spain, Sweden, Switzerland, UK and Israel; (ii), includes 10 countries: Bulgaria, Croatia, Czech Republic, Georgia, Hungary, Latvia, Poland, Russia, Slovakia and Serbia-Montenegro and (iii), includes four countries: Argentina, Brazil, Chile and Me xico. HRQL assessment The national language translation of the parent s administered 50-item version of the CHQ (also called CHQ-PF 50) [14, 16] was used to assess HRQL of patients and healthy children. The CHQ is a generic self-administered instrument designed to capture the physical, emotional and social components of health status of children from 5 18 yrs of age. The CHQ comprises 15 health concepts: global health (GGH), physical functioning (PF), role/social limitations emotional/behavioural (REB), role/social limitations physical (RP), bodily pain/discomfort (BP), behaviour (BE), general behaviour (GBE), mental health (MH), self-esteem (SE), general health perception (GH), change in health (CH), parent impact-emotional (PE), parent impact-time (PT), family activities (FA) and family cohesion (FC). The questionnaire is completed by a parent, who is asked to recall the preceding 4-week period for all subscales except for the GGH, GH and FC scales; the recall period for CH is compared to last year. Because the GGH, GH and FC subscales ask about health and family relationships in general, no recall period is used. Scores for each subscale range from 0 to 100, with higher scores reflecting better health status. In addition, two summary measures have been created by factor analysis through the aggregation of 10 of the 15 subscales (PF, RP, BP, GH, REB, PT, PE, SE, MH, BE): the physical summary score (PhS) and the psychosocial summary score (PsS). These have been standardized by multiplying the standard score by 10 and adding 50 to the product. This yields a distribution of score with a mean of 50 and an S.D. of 10. Higher scores in the scales indicate better HRQL. CHQ scores were calculated using the proprietary algorithms and SAS programming code created specifically for the CHQ by the developer as detailed in the manual [14]. Functional ability assessment A parent of each patient (generally the mother) was asked to complete the national language version of the CHAQ [13, 16]. The CHAQ measures the child s ability in performing functions included in eight areas (dressing and grooming, arising, eating, walking, hygiene, reach, grip and activities) for a total item number of 30. Respondents are directed to note only those difficulties caused by arthritis. Each question is scored from 0 to 3 (0 ¼ no difficulty, 1 ¼ some difficulty, 2 ¼ much difficulty, 3 ¼ unable to do so). The question with the highest score determines the score for that functional area. If aids or devices are used or help is needed to complete tasks in a certain area, a minimum score of 2 is recorded for the corresponding functional area. The scores for each of the eight functional areas are averaged to calculate the CHAQ disability index (DI), which ranges from 0 to 3 (0 ¼ best; 3 ¼ worst). The parent s version of the CHAQ incorporates also a doubly-anchored horizontal 10 cm visual analogue scale (VAS) for the assessment of the child s overall well-being (with anchors of 0 ¼ very well and 10 ¼ very poor ) and a doubly-anchored horizontal 10 cm VAS for the assessment of the intensity of the child s pain (with anchors of 0 ¼ no pain and 10 ¼ very severe pain ). Assessment of JIA severity measures The following measures of JIA severity were assessed in each patient by the attending physician: number of joints with swelling (range 0 62); number of joints with tenderness/pain on passive motion (range 0 75); number of joints with limited range of motion (range 0 67); number of joints with active arthritis (defined as the number of joints with swelling or, if no swelling was present, with limitation of movement with either pain upon movement or tenderness) (range 0 71) [19]; physician s global assessment of the overall disease activity on a doubly-anchored 10 cm VAS (anchoring words: 0 ¼ inactive, 10 ¼ very severe ). The laboratory indicator of systemic inflammation was the Westergren erythrocyte sedimentation rate (ESR). Statistics Descriptive statistics were reported in terms of means and S.D. for the continuous variables and in terms of absolute frequencies and percentages for the categorical variables. Statistical tests included Student s t-test, Mann Whitney U-test (MW), chi-square test or the Fisher s exact test, as appropriate. A one-way analysis of variance (ANOVA) with Scheffe test for post hoc comparisons, was conducted in order to evaluate differences between the countries belonging to each geographic area (within geographic area analysis), and among the three geographic regions (between geographic area analysis). All statistical tests were two-sided. Owing to the large size of the study sample, all comparisons between patients and healthy

3 316 R. Gutiérrez-Sua rez et al. children were statistically significant and therefore only P-value of <0.001 were considered for the qualitative interpretation of the data. We chose to evaluate, through logistic regression procedures with backward strategy, determinants of poor HRQL as defined by dichotomized CHQ summary scores (PhS and PsS) with cut-points set at <30 (<2 S.D. of the mean of healthy children) (poorer HRQL) and 30 (better HRQL); we choose as cut-off <2 S.D. to concentrate on the patients who have the poorest HRQL as measured by the CHQ. The overall hypothesis was that JIA is a disease that affects mainly the physical rather than the psychosocial components of health, and therefore determinants would have a stronger influence on the physical well-being than on the psychosocial well-being; we also hypothesized that determinants will be the same irrespective of the geographic area of origin of the patient. Possible explanatory variables assessed were all those included in Table 1 and the geographic area of origin of the patients; variables were dichotomized according to the best threshold obtained from the receiver operating characteristic (ROC) curve analysis [20]. Dichotomization of explanatory variables has the advantage of providing clinical meaningful odd ratios (OR) with 95% confidence interval (95% CI). Statistical significance was tested by means of the likelihood ratio test (LR-test); in multivariate analysis a P-value <0.05 was considered statistically significant. The statistical package Statistica (StatSoft Corp., Tulsa, OK, USA) for univariate analyses and the Stata release 7 (Stata Corp., College Station, TX, USA) for multivariate analyses, were used. Results Demographic, JIA severity and parent s reported measures assessment A total of 6290 eligible subjects (3167 with JIA and 3123 healthy children) younger than 18 yrs were included in this study from the following 30 countries divided in three geographic regions as follows: (i) from (2102 JIA and 2064 healthy children): Austria (n ¼ 131), Belgium (n ¼ 203), Denmark (n ¼ 134), Finland (n ¼ 162), France (n ¼ 495), Germany (n ¼ 199), Greece (n ¼ 134), Italy (n ¼ 1189), Netherlands (n ¼ 187), Norway (n ¼ 152), Portugal (n ¼ 120), Spain (n ¼ 152), Sweden (n ¼ 130), Switzerland (n ¼ 151), UK (n ¼ 477) and Israel (n ¼ 150); (ii) from (668 JIA and 550 healthy children): Bulgaria (n ¼ 129), Croatia (n ¼ 139), Czech Republic (n ¼ 148), Georgia (n ¼ 110), Hungary (n ¼ 125), Latvia (n ¼ 141), Poland (n ¼ 30), Russia (n ¼ 142), Slovakia (n ¼ 121) and Serbia-Montenegro (n ¼ 133) and (iii) from (397 JIA and 509 healthy children): Argentina (n ¼ 117), Brazil (n ¼ 486), Chile (n ¼ 121) and Me xico (n ¼ 182). The main demographic, JIA severity measures and parent s reported measures from the three geographic areas are reported in Table 1. In the between-geographic area analysis the group had a statistically significant lower mean age of onset and a higher proportion of females in comparison with the other two regions (P < for both). The ILAR category of JIA patients was systemic arthritis in 613 (19.4%), polyarthritis in 1069 (33.7%), extended oligoarthritis in 567 (17.9%) and persistent oligoarthritis in 918 (29%). Patients from Western Europe group in comparisons with the and Latin America had a higher number of cases with extended oligoarthritis (21.5 vs 12 vs 9%, respectively, P-value <0.001), and lower frequency of systemic subtypes (16.4 vs 23.2 vs 28.5%, respectively, P-value <0.001). With regard to the JIA severity measures patients from and experience a more severe disease when compared with as showed by a higher number of active joints, joints with limitation on motion and joints with pain. Disability as measured by the CHAQ was also higher in children coming from while the parent s assessment of child pain was lower in JIA patients from (both P < 0.001). The physicians evaluation of disease activity, the number of joints with swelling, ESR and the parent s assessment of the child s well-being were similar among the three areas. When the analysis was devoted to evaluate differences among countries belonging to the same geographic areas (within-geographic area analysis) no statistically significant difference were found for the demographic variables (data not shown). However, for disease-related measures, children from UK, when compared with the remaining countries, showed a more severe disease as expressed by a TABLE 1. Demographic, clinical and laboratory characteristics of the sample. All values are expressed as means S.D. unless otherwise specified All regions (n ¼ 3167) (n ¼ 2102) (n ¼ 668) (n ¼ 397) Age of onset, yrs Visit age, yrs Disease duration, yrs Female No. (%) 2167 (78%) 1484 (83.2) 428 (72.1) 255 (68.3) JIA subtype Systemic. No. (%) 613 (19.4) 345 (16.4) 155 (23.2) 113 (28.5) Polyarticular No. (%) 1069 (33.7) 686 (32.6) 222 (33.2) 161 (40.6) Extended oligoarticular No. (%) 567 (17.9) 451 (21.5) 80 (12.0) 36 (9.0) Persistent oligoarticular. No. (%) 918 (29.0) 620 (29.5) 211 (31.6) 87 (21.9) JIA severity measures Physician s global assessment of disease activity (0 10 cm VAS) No. of active joints No. of joints with limitation on motion No. of joints with swelling No. of joints with pain ESR Parents reported measures CHAQ disability index (0 3 score) Parent s assessment of child s well-being (0 10 cm VAS) Parent s assessment of child s pain (0 10 cm VAS) ANOVA P < 0.001; chi-square P <

4 HRQL of life of patients with juvenile idiopathic arthritis 317 Figure 1 illustrates the mean values of the 15 subscales of the CHQ and the two summary scores in the three areas; the vertical bar at the top of each column represents a value that is <2 S.D. of the means of healthy children. Dichotomization of CHQ scores in JIA patients according to the values observed in healthy children showed that 235 (13%), 71 (12%) and 48 (13%) in, and, patients had a PhS <2 S.D., respectively, and that 70 (4%), 11 (2%) and 15 (4%) of the patients had a PsS < 2 S.D. of healthy children, respectively. There were no differences in the mean PhS and in the mean PsS of the CHQ of the three geographic areas. Compared with healthy children, JIA patients had lower values in all subscales of the CHQ with the most impaired domains (<2 S.D. of the means of healthy children in one or more higher mean score of the Physician s global assessment of disease activity (3.9 vs 2.7), number of active joints (8.4 vs 4.7), CHAQ-DI (1.2 vs 0.7) and parent s VAS of overall well-being (3.5 vs 2.3) (P < 0.001). Similarly, in, children from Russia had a higher mean value of the parent s VAS of overall well-being (3.9 vs 2.6) in contrast with other children from the same region (P < 0.001). Also, Mexican children when compared with the other n countries showed a higher mean number of active joints (9.3 vs 5.7), number of joints with limitation on motion (15.7 vs 7.3) and CHAQ-DI (1.2 vs 0.7) (P < 0.001). HRQL assessment The CHQ and the CHAQ were completed by the mother in 81% and in 19% by the father or guardians Physical functioning (PF) Role/social limitations emotional behavioural (REB) Role/social limitations physical (RP) Bodily pain/discomfort (BP) Behaviour (BE) Global behaviour (GBE) Mental health (MH) Self-esteem (SE) General health perceptions (GH) Change in health (CH) Parental impact emotional (PE) Parental impact time (PT) Family activities (FA) Family cohesion (FC) Physical summary score (PhS) Psychological summary score (PsS) FIG. 1. Mean and 95% CI of the 15 subscales (range 0 100) and the two summary scores (norm-based values with mean of 50 and S.D. of 10) of the CHQ. Higher scores indicate better health. Vertical bars represent 2 S.D. of the mean of healthy children. The white arrows (G) on the right of the graphs indicate the 4 CHQ health concepts (GGH, PF, BP and GH) that are <2 S.D. of the mean of healthy children. The arrows with asterisks ( ) indicate the CHQ health concepts that are statistically significant different among the three geographic areas (GGH, BP, SE, GH, CH and FC). Global health (GGH) 60 H

5 318 R. Gutiérrez-Sua rez et al. geographic areas) being PF, BP, GGH and GH (see white arrows in Fig. 1). Statistically significant differences (P < 0.001) were found among the three geographic regions for the following CHQ subscales: BP, GGH, GH, CH with respect to the previous year, SE and FC (see arrows with asterisks () in Fig. 1). When the analysis was devoted to evaluate differences among countries belonging to the same geographic areas, similarly to the differences found for the JIA severity measures, children from UK, Russia and Me xico showed lower values in several CHQ subscales when compared with the remaining countries of the same geographic area (data not shown). In order to evaluate the robustness of the differences found in the HRQL and JIA severity measures for UK, Russia and Me xico, the within-geographic group analysis was repeated excluding these three countries from the related area and no statistically significant differences were found between the remaining countries for any of the HRQL and JIA severity measures considered. Analysis of determinants of poor HRQL As detailed in the methods section, poor HRQL was defined by a physical well-being (PhS) or psychosocial well-being (PsS) <30 that is <2 S.D. below normal for healthy children. In univariate analyses, we found that all clinical measures of JIA severity (physician s and parent s global assessments, joint counts, CHAQ score and ESR) were significantly related to the dichotomized PhS and PsS (P < for all variables). Of the demographic and clinical variables reported in Table 1, only the disease duration and the JIA subtype were significantly associated with PhS and/or PsS. All variables that were significantly associated with the two dichotomized outcomes in univariate analyses were entered in the logistic regression procedures. The best-fitted logistic regression models to identify, for the three geographic areas, and for the whole cohort, the determinants of poor PhS and PsS well-being are reported in Table 2 and Table 3, respectively. The CHAQ -DI was the strongest determinant for poor PhS for all three regions with OR ranging from 4.8 in to 5.5 in and 7.3 in, followed by a parent s assessment of child s pain, the parent s assessment of child s overall well-being, ESR and the physician assessment of disease activity. The determinants for poor PsS are reported in Table 3. The parent s assessment of child s pain was the strongest determinant found to be predictive for poor psychosocial well-being in Western Europe and. Parent s assessment of child s overall well-being turned out to be a less important predictor for a poor outcome but only in. Discussion In this study, we analysed the PRINTO database to evaluate the HRQL of children with JIA coming from three different geographic areas. The results showed that in general, children with JIA when compared with healthy children, have a poorer HRQL as measured by the CHQ. The most affected health concepts (<2 S.D. from healthy children) were PF, BP, GGH and GH. Overall, there was an important impact more on the physical well-being than on the psychosocial well-being. All the other CHQ health concepts and the two summary scores were closer to that observed in healthy children. These observations generally suggest that parents are concerned about the health of their child s well-being, their level of pain and physical functioning irrespective of the area of origin. Health concepts that differentiate the three geographic areas were greatly overlapping with the list of the most impaired domains and include BP, GGH, GH, CH with respect to the previous year, SE and FC. Pain is the most important symptom in arthritis and is thought to be closely related to psychological factors, adaptation to a chronic disease and geographic/cultural/ socio-economic differences [4, 10 12, 21]. These observations can probably explain why the level of bodily pain/discomfort as measured by the CHQ was one of the differentiating factors of the TABLE 2. Best-fitted logistic regression model to identify demographic, clinical and laboratory determinants for poor physical well-being defined as a physical summary score (PhS) <30 that is <2 S.D. below the mean of healthy children HRQL determinants (ROC cut-off) All (n ¼ 2437) OR (95% CI) Outcome: CHQ (PhS) summary score (<30) (n ¼ 1529) OR (95% CI) (n ¼ 564) OR (95% CI) (n ¼ 344) OR (95% CI) CHAQ disability index (>1) 5.1 ( ) 5.5 ( ) 7.3 ( ) 4.8 ( ) Parents assessment of child s pain (>3.4) 2.6 ( ) 3.1 ( ) 3.7 ( ) Parents assessment of child s well-being (>3.7) 2.1 ( ) 2.4 ( ) 3.1 ( ) ESR (>32) 2.2 ( ) 2.8 ( ) 2.1 ( ) MD disease activity assessment (>3.4) 1.5 ( ) 2.7 ( ) P < ; P < 0.001; P < 0.01; P < TABLE 3. Best-fitted logistic regression model to identify demographic, clinical and laboratory determinants for poor psychosocial well-being defined as a psychosocial summary score (PhS) <30 that is <2 S.D. below the mean of healthy children Outcome: CHQ (PsS) summary score (<30) HRQL determinants (ROC cut-off) All (n ¼ 2437) OR (95% CI) (n ¼ 1529) OR (95% CI) Clinical status measures Parent s assessment of child s pain (>3.4) 7.5 ( ) 5.5 ( ) Parent s assessment of child s well-being (>3.7) 2.2 ( ) P < ; P < a None of the variables turned out to be statistically significant for. (n ¼ 564) OR (95% CI) a a (n ¼ 344) OR (95% CI) 14.1 ( )

6 HRQL of life of patients with juvenile idiopathic arthritis 319 three areas examined, with children coming from experiencing more pain than their counterpart in and. Within each geographic area, the HRQL was generally similar across countries but with some exception represented by children followed in UK, Russia and Me xico who tend to have a more severe disease and a poorer HRQL when compared with the other countries of the same geographic area. To this regard, it should be noticed that the differences observed for these three countries are probably related to the fact that most of the children present in the database came from national referral centres from big cities (London, Moscow and Me xico City, respectively). Other differences were found in the demographic and clinical characteristics of the patients with JIA coming from Western Europe having a lower mean age of onset, a higher proportion of females higher number of cases with extended oligoarthritis and lower frequency of systemic subtypes when compared with children coming from and. This might reflect differences in genetic and/or environmental factors that affect disease aetiopathogenesis. When the analysis was devoted to the differences in JIA severity measures, we observed that JIA patients from were generally less severe than those in and for what concerns most of the articular parameters, the level of disability and pain probably reflected by the difference observed in the clinical phenotype of the disease and/or in the availability of access to the health-care system. These observations were further confirmed by the results of the logistic regression analysis that showed that a poor physical well-being was mostly affected by the level of disability, and to a lesser extent by the intensity of pain and the level of disease severity. Indeed, disability is considered the most significant outcome of arthritis [4] and this study shows that it is important for poor physical well-being across the geographic areas examined. Determinants of poor psychosocial well-being were mainly related to the level of pain and overall well-being of the JIA patients as assessed by parents and were identified only for Western and. To the best of our knowledge, this is the only international study carried out to investigate differences in the HRQL in children with JIA from three different geographic areas. It is therefore difficult to compare our results with other investigations that were concerned with other chronic conditions or with the adult population [4, 6 12]. We must acknowledge the study limitation due to the fact that we did not thoroughly considered other socio-cultural variables as socio-economic status, educational attainment, parents marital status, ethnicity or religion, that is often linked to poor outcome. Another potential limitation is due to the fact that some of the children with JIA in this study came from regional/national referral centres where more severe patients might be observed who are not representative of the whole spectrum of disease severity. Usually cross-cultural comparison come from studies conducted in single or few countries often with diverse methodological approaches in terms of type of patients, clinical and HRQL measures collected making such comparisons therefore impossible. The major advantages of our study were that the same protocol had been applied for data collection for all participating centres, and the availability of the CHAQ [13] and CHQ [14] cross-culturally adapted and validated into several languages [16] according to existing guidelines [17], that ensures that most of the non-disease-related factors were taken into account. In conclusion, we found that patients with JIA have a significant impairment of their HRQL compared with healthy peers, particularly in the physical domain. Disability and pain are the most important determinants of physical and psychosocial well-being irrespective of the geographic area of origin. Rheumatology Key messages Juvenile idiopathic arthritis patients from Western or or have impaired HRQL. Disability and pain are the most important determinants of physical and psychosocial well-being. Acknowledgements We thank the European Union for the support to the project (contract No. BMH CA and AML/B7-311/97/0666/II FI). We are indebted to the PRINTO national co-ordinators who managed the work of the paediatric rheumatology centres of each country for data collection, and to the families of the JIA patients and of healthy children who allowed us to study their children. List of additional PRINTO national co-ordinators who participated in the quality of life project: Anne Marie Prieur, MD, Paris, France; Claudia Machado, MD, Botucatu, Brasil; Kevin J. Murray, MBBS, FRACP, Perth, Australia; Sang-Cheol Bae, MD, PhD, Seoul, Korea; Rik Joos, MD, Gent, Belgium; Ivan Foeldvari, MD, Hamburg, and Hans-Iko Huppertz, Prof. Dr Med., Bremen, Germany; Carolina Duarte-Salazar, MD, Tlalpan, Me xico, D.F., Me xico; Nico Wulffraat, MD and Wietse Kuis, MD, PhD, Utrecht, Netherlands; Pekka Lahdenne, MD, Helsinki, Finland; Pavla Dolezalova, MD, PhD, Praha, Czech Republic; Jaime de Inocencio, MD, Madrid, Spain; Florence Kanakoudi-Tsakalidou, MD, Prof. Thessaloniki, Greece; Michael Hofer, MD, Lausanne, Switzerland; Irina Nikishina, MD, Moscow, Russia; Huri Ozdogan, MD Istanbul, Turkey; Pat Woo, London, UK and Phil Hashkes, MD, Cleveland, OH, USA. The authors have declared no conflicts of interest. References 1. Foster HE, Marshall N, Myers A, Dunkley P, Griffiths ID. Outcome in adults with juvenile idiopathic arthritis a quality of life study. Arthritis Rheum 2003;48: Ruperto N, Buratti S, Duarte-Salazar C et al. 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