Health Care Utilization and Direct Costs Prior to Subspecialty Care in Children with Chronic Pain Compared with Other Chronic Childhood Diseases: A Cohort Study.

OBJECTIVES: To understand the burden associated with pediatric chronic pain (CP) on the health care system compared with other costly chronic diseases prior to subspecialty care. STUDY DESIGN: In this retrospective cohort study, we assessed all-cause health care utilization and direct health care costs associated with pediatric CP (n = 91) compared with juvenile arthritis (n = 135), inflammatory bowel disease (n = 90), type 1 diabetes (n = 475) or type 2 diabetes (n = 289), anxiety (n = 7193), and controls (n = 273) 2 and 5 years prior to patients entering subspecialty care in Manitoba, Canada. Linked data from physician encounters, emergency department visits, hospitalizations, and prescriptions were extracted from administrative databases. Differences in health care utilization and direct health care costs associated with CP vs the other conditions were tested using negative binomial and zero-inflated negative binomial regression models, respectively. RESULTS: After adjustment for age at diagnosis, sex, location of residence, and socioeconomic status, CP continued to be associated with the highest number of consulted physicians and subspecialists and the highest number of physician billings compared with all other conditions (P < .01, respectively). CP was significantly associated with higher physician costs than juvenile arthritis, inflammatory bowel disease, type 1 diabetes, type 2 diabetes, or controls (P < .01, respectively); anxiety was associated with the highest physician and prescription costs among all cohorts (P < .01, respectively). CONCLUSION: Compared with chronic inflammatory and endocrinologic conditions, pediatric CP and anxiety were associated with substantial burden on the health care system prior to subspecialty care, suggesting a need to assess gaps and resources in the management of CP and mental health conditions in the primary care setting.

A new Canadian inception cohort for juvenile idiopathic arthritis: The Canadian Alliance of Pediatric Rheumatology Investigators Registry.

OBJECTIVES: The aim was to describe the design, methods and initial findings of a new Canadian inception cohort of children with JIA, The Canadian Alliance of Pediatric Rheumatology Investigators (CAPRI) JIA Registry. METHODS: The CAPRI JIA Registry was started in 2017 to collect information prospectively on children enrolled within 3 months of JIA diagnosis across Canada. The registry has a non-traditional modular design, with no artificially set times for registry visits to occur, streamlined multi-method data collection that requires 2-4 min per visit, and reports cumulative incidence of treatments, outcomes and adverse events calculated by Kaplan-Meier survival methods. RESULTS: A total of 166 patients, enrolled a median of 6 weeks after JIA diagnosis at 10 centres, were included. The median age at diagnosis was 9 years [interquartile range (IQR) 3, 13], 61% were female and 51% had oligoarticular JIA. The median three-variable clinical Juvenile Arthritis Disease Activity Score was 6.5 (IQR 4, 10) at enrolment, and the median time to first attainment of clinically inactive disease (CID) was 24 weeks (by 1 year, 81%). Within 1 year of diagnosis, 70% of patients had started a DMARD and 35% a biologic agent. The rates of adverse events and serious adverse events were 60 and 5.8 per 100 patient-years, respectively. CONCLUSION: This streamlined and flexible registry minimizes the burden of data collection and interference with clinic operations. Initial findings suggest that treatments for newly diagnosed patients with JIA in Canada have intensified, and now 81% of patients attain CID within 1 year of diagnosis.

An overlapping phenotype of Osteogenesis imperfecta and Ehlers-Danlos syndrome due to a heterozygous mutation in COL1A1 and biallelic missense variants in TNXB identified by whole exome sequencing.

Osteogenesis imperfecta (OI) and Ehlers-Danlos syndrome (EDS) are variable genetic disorders that overlap in different ways [Cole 1993; Grahame 1999]. Here, we describe a boy presenting with severe muscular hypotonia, multiple fractures, and joint hyperflexibility, features that are compatible with mild OI and hypermobility type EDS, respectively. By whole exome sequencing, we identified both a COL1A1 mutation (c.4006-1G > A) inherited from the patient's mildly affected mother and biallelic missense variants in TNXB (p.Val1213Ile, p.Gly2592Ser). Analysis of cDNA showed that the COL1A1 splice site mutation led to intron retention causing a frameshift (p.Phe1336Valfs*72). Type 1 collagen secretion by the patient's skin fibroblasts was reduced. Immunostaining of a muscle biopsy obtained from the patient revealed a clear reduction of tenascin-X in the extracellular matrix compared to a healthy control. These findings imply that the combination of the COL1A1 mutation with the TNXB variants might cause the patient's unique phenotype.

Elevated blood eosinophils in early infancy are predictive of atopic dermatitis in children with risk for atopy.

BACKGROUND: Accessible markers to predict the development of atopic diseases are highly desirable but yet matter of debate. OBJECTIVE: We investigated the role of blood eosinophils at 4 weeks and 7 months of life and their association with developing atopic dermatitis (AD) in a birth cohort of children with atopic heredity. METHODS: Infant blood samples for eosinophil counts were taken from 559 infants at 4 weeks and from 467 infants at 7 month of life with at least one atopic parent. Elevation of blood eosinophils was defined as ≥ 5% of total leukocytes and the asscociation for the occurrence of AD was assessed by entering 2 × 2 tables and the odds ratios were estimated followed by hypothesis testing against the alternate working hypothesis: odds ratio < > 1. Survival analysis was carried out estimating the Kaplan-Meier product limit estimator from the life-time table of AD score and time to AD manifestation stratified by the eosinophil binary score. RESULTS: Elevated blood eosinophils observed at 4 weeks were significantly associated with the occurrence of AD in the whole cohort at the age of 7 months (p = 0.007), 1 year (p = 0.004), 2 years (p = 0.007) and 3 years (p = 0.006) of life. AD occurred app. 12 weeks earlier in infants with elevated blood eosinophils at 4 weeks of life. Blood eosinophil counts ≥5% at 7 months of life failed to show significance for AD; for eosinophils at 4.5% a significant association at 7 months (p = 0.005), and 1 year of life (p = 0.039), 2 years (p = 0.033) and 3 years (p = 0.034) was observed. CONCLUSION: Elevated blood eosinophils at age 4 weeks have a predictive value for the onset of atopic dermatitis in infancy and early childhood in children with high risk for atopy. Early eosinophil counts may therefore be helpful for counseling parents to provide infant skincare but furthermore identify individuals for interventional trials aiming at allergy prevention.

Health-related quality of life in patients with long-standing rheumatoid arthritis in the era of biologics: data from the German biologics register RABBIT.

OBJECTIVE: To compare the 24-month course of health-related quality of life (HRQoL) in patients with long-standing RA treated with a conventional synthetic (cs) or a first, second or third biologic (b) DMARD in daily rheumatological care. METHODS: Patients enrolled in the German biologics register RABBIT who were observed over at least 12 months were stratified according to the nth bDMARD started at enrolment. HRQoL was captured by the SF36 health survey. Within strata of sequential bDMARD therapy, we examined patients' HRQoL at baseline and at follow-ups in comparison with the general population, the 24-month course of HRQoL of different bDMARDs and the proportion of patients exceeding the minimal detectable improvement of physical and mental health sum scores. RESULTS: All patients reported remarkably lower scores of physical and mental health than the general population at baseline and month 12. In each stratum of sequential bDMARD therapy, patients improved significantly by month 12 and remained stable until month 24. The improvement of HRQoL was not attributable to a particular bDMARD. The following proportions of patients exceeded the minimal detectable improvement of at least 17.85 Physical Component Scale scores or 22.18 Mental Component Scale score points: csDMARD (n = 1113) 31.1%/22.3%, first bDMARD (n = 1352) 39.9%/29.7%, second bDMARD (n = 730) 37.3%/26.2% and third bDMARD (n = 680) 34.2%/30.9%. CONCLUSION: Lasting improvement of both physical and mental health is achievable even for severely affected RA patients with a history of more than one bDMARD failure. Nevertheless, impairment of HRQoL in RA patients is enormous compared with the general population.

Establishment of the intestinal microbiota and its role for atopic dermatitis in early childhood.

BACKGROUND: Perturbations in the intestinal microbiota may disrupt mechanisms involved in the development of immunologic tolerance. The present study aimed to examine the establishment of the infant microbiota and its association to the development of atopic dermatitis (AD). METHODS: Within a randomized, placebo-controlled trial on the prevention of AD by oral supplementation of a bacterial lysate between week 5 and the end of month 7, feces was collected at the ages of 5 weeks (n = 571), 13 weeks (n = 332), and 31 weeks (n = 499) and subjected to quantitative PCRs to detect bifidobacteria, bacteroides, lactobacilli, Escherichia coli, Clostridium difficile, and Clostridium cluster I. RESULTS: Birth mode, breast-feeding but also birth order had a strong effect on the microbiota composition. With increasing number of older siblings the colonization rates at age 5 weeks of lactobacilli (P < .001) and bacteroides (P = .02) increased, whereas rates of clostridia decreased (P < .001). Colonization with clostridia, at the age of 5 and 13 weeks was also associated with an increased risk of developing AD in the subsequent 6 months of life (odds ratioadjusted = 2.35; 95% CI, 1.36-3.94 and 2.51; 1.30-4.86, respectively). Mediation analyses demonstrated that there was a statistically significant indirect effect via Clostridium cluster I colonization for both birth mode and birth order in association to AD. CONCLUSION: The results of this study are supportive for a role of the microbiota in the development of AD. Moreover, the "beneficial" influence of older siblings on the microbiota composition suggests that this microbiota may be one of the biological mechanisms underlying the sibling effect.

The risk of infections associated with rheumatoid arthritis, with its comorbidity and treatment.

RA is known to be associated with an increased risk of serious infection. Even more than 50 years ago, observational studies showed a greater than 2-fold increased risk of serious infection in RA. This was reinforced by various subsequent cohort studies. The elevated susceptibility of patients with RA can be explained by the pathobiology of the disease itself, the impact of chronic comorbid conditions, as well as sequelae of immunosuppressive treatment. It has been suggested that premature ageing of the immune system in RA contributes to weakened protection against infectious organisms. In addition, chronic comorbid conditions such as diabetes or chronic lung or kidney disease, disease-related functional disability, as well as lifestyle factors such as smoking, increase the risk in individual patients. For a long time glucocorticoids (GCs) have been used as potent immunosuppressive drugs in RA. There is evidence that they increase the risk of serious infections up to 4-fold in a dose-dependent manner. TNF-α inhibitors increase the serious infection risk up to 2-fold. They have, however, the potential to outweigh their risk when higher GC doses can be tapered down. If patients need higher dosages of GCs in addition to treatment with biologic agents, their risk of infection is substantial. This combination should be used carefully and, if possible, avoided in patients with additional risk factors such as older age or comorbid conditions.

Oral application of bacterial lysate in infancy decreases the risk of atopic dermatitis in children with 1 atopic parent in a randomized, placebo-controlled trial.

BACKGROUND: Lower prevalence of atopy was found in children with continuous exposure to livestock and thus to microbial compounds. In animal models exposure to endotoxin (LPS) decreases allergic sensitization and airway inflammation. OBJECTIVE: We sought to evaluate the effect of orally applied bacterial lysate in infancy on the prevalence of atopic dermatitis (AD) after the treatment phase at 7 months of age. METHODS: This randomized, placebo-controlled trial included 606 newborns with at least single heredity for atopy. From week 5 until the end of month 7, infants were treated orally with bacterial lysate containing heat-killed gram-negative Escherichia coli Symbio and gram-positive Enterococcus faecalis Symbio or its placebo. Children were followed until 3 years of age. RESULTS: There was no difference in the primary outcome between the active and placebo groups in the total study group. AD prevalence was significantly reduced at the end of the intervention phase (31 weeks of age) in the subgroup of infants with single heredity for atopy (relative risk, 0.52; 95% CI, 0.3-0.9). Ten percent (15/154) of infants in the active group had AD compared with 19% (27/145, P = .030) in the placebo group. This was more pronounced in the group of infants with paternal heredity for atopy (11% vs 32%, P = .004; relative risk, 0.34; 95% CI, 0.2-0.7). CONCLUSION: Feeding of bacterial lysate might have prevented the development of AD, especially in children with paternal atopy, possibly indicating a preventive property only in subjects with a limited risk for atopy.

Anaphylaxis to etanercept in two children with juvenile idiopathic arthritis.

Anti-tumor necrosis factor α (TNFα) medications have revolutionized the care of children and adults with chronic arthritis. They are quick acting, highly effective, and remarkably safe, particularly in children with juvenile idiopathic arthritis (JIA). Anti-TNFα agents come in 2 basic varieties: monoclonal antibodies to TNFα (e.g., infliximab, adalimumab) and a fusion protein containing a TNF receptor (etanercept). Although hypersensitivity reactions are not uncommon with some of the TNFα antibodies (e.g., infliximab), there are only rare reports of anaphylaxis to subcutaneous injections of etanercept in adults with rheumatoid arthritis. Herein, we report 2 cases of anaphylaxis in children with JIA after etanercept injections. Although rare, pediatricians need to be aware of this potentially dangerous occurrence.

Collaborating with a Youth Council to Improve Chronic Pain Resources.

Background: There is a recognized need to involve people with lived experience of chronic pain when developing chronic pain resources. Aims: The aim of this study was to develop, implement, and evaluate a short-term youth council focused on eliciting youths' recommendations for key features of chronic pain informational resources. Methods: In this mixed methods instrumental case study, demographic data were collected via Survey Monkey®. Select Patient-Reported Outcomes Measurement Information System® brief measures were used to provide context regarding pain impact within this group. Participants completed an initial interview, which informed youth council workshop delivery. Over two youth council workshops, participants reviewed select informational resources and identified key features of chronic pain resources. Participants evaluated their involvement experience during a second interview. Qualitative data were transcribed and analyzed using directed content analysis. Member-checking occurred during a third workshop, held virtually. Results: Seven youth self-identifying as girl/woman or demi-girl participated. The youth were satisfied with the youth council experience, highlighting the importance of meeting others, a relaxed environment, and participating in valuable work. A list of youth-identified key features for informational resources was created through the workshops, which includes considerations for audience groups, content, and presentation. Conclusion: Participants' input into youth council development and meeting others with lived experience contributed to a safe and supportive involvement experience. Youth council involvement supported the development of preliminary recommendations for chronic pain informational resources.

Contexte: Il est largement reconnu qu'il est essentiel d'impliquer les individus ayant une expérience personnelle de la douleur chronique dans le processus de création de ressources sur la douleur chronique.Objectifs: Cette étude visait à établir, mettre en œuvre et évaluer un conseil consultatif composé de jeunes, à court terme, dans le but d'obtenir leurs recommandations concernant les caractéristiques essentielles des ressources d'information sur la douleur chronique.Méthodes: Dans le cadre de cette étude de cas instrumentale utilisant une approche mixte, des données démographiques ont été collectées via Survey Monkey®. Des mesures brèves du Système d'information sur les mesures des résultats déclarés par les patients® ont été sélectionnées pour contextualiser l'impact de la douleur au sein de ce groupe. Les participants ont ensuite complété un entretien initial, qui a servi de base pour la mise en œuvre de l'atelier du conseil des jeunes. Au cours de deux ateliers du conseil des jeunes, les participants ont examiné des ressources d'information sélectionnées et ont déterminé quelles devaient être les principales caractéristiques des ressources en matière de douleur chronique. Les participants ont évalué leur expérience de participation au cours d'un deuxième entretien. Les données qualitatives ont été transcrites et analysées à l'aide d'une analyse de contenu dirigée. Une vérification par les membres a été effectuée lors d'un troisième atelier, qui s'est tenu virtuellement.Résultats: Sept jeunes s'identifiant comme filles/femmes ou demi-filles ont participé à l'étude. Les jeunes se sont déclarés satisfaits de leur expérience au sein du conseil des jeunes, soulignant l'importance de rencontrer d'autres jeunes, d'un environnement détendu et de la participation à un travail utile. Une liste des caractéristiques clés identifiées par les jeunes pour les ressources d'information a été dressée au cours des ateliers. Celle-ci comprenait notamment des considérations relatives aux groupes cibles, au contenu et à la présentation.Conclusion: La contribution des participants à l'élaboration du conseil des jeunes et la rencontre avec d'autres personnes ayant une expérience personnelle ont contribué à une expérience de participation sûre et positive. La participation du Conseil des jeunes a contribué à l'élaboration de recommandations préliminaires concernant les ressources d'information sur la douleur chronique.

Do Patterns of Early Disease Severity Predict Grade 12 Academic Achievement in Youths With Childhood-Onset Chronic Rheumatic Diseases?

OBJECTIVE: To test the association of early disease severity with grade 12 standards test performance in individuals with childhood-onset chronic rheumatic diseases (ChildCRDs), including juvenile arthritis and systemic autoimmune rheumatic diseases. METHODS: We used linked provincial administrative data to identify patients with ChildCRDs born between 1979 and 1998 in Manitoba, Canada. Primary outcomes were Language and Arts Achievement Index (LAI) scores and Math Achievement Index (MAI) scores from grade 12 standards test results as well as enrollment data. The secondary outcome was enrollment in grade 12 by 17 years of age. Latent class trajectory analysis identified disease severity groups using physician visits following diagnosis. Multivariable linear regression tested the association of disease severity groups with LAI and MAI scores, and logistic regression tested the association of disease severity with age-appropriate enrollment, after adjusting for sociodemographic factors and psychiatric morbidities. RESULTS: The study cohort included 541 patients, 70.1% of whom were female. A 3-class trajectory model provided the best fit; it classified 9.7% of patients as having severe disease, 54.5% as having moderate disease, and 35.8% as having mild disease. After covariate adjustment, severe disease was associated with poorer LAI and MAI scores but not with age-appropriate enrollment. CONCLUSION: Among patients with ChildCRDs, those with severe disease performed more poorly on grade 12 standards tests, independent of sociodemographic and psychiatric risk factors. Clinicians should work with educators and policy makers to advocate for supports to improve educational outcomes of patients with ChildCRDs.

Understand me: Youth with chronic pain on how knowledge gaps influence their pain experience.

Background: There is a perceived lack of readily available resources to support self-management skills in youth living with chronic pain. The perspectives of youth regarding information gaps may improve the effectiveness of resources developed for them. Aim: The aim of this study was to explore the perspectives of youth living with chronic pain on the interactions among their pain experiences, chronic pain resources and research. Methods: Using an interpretive paradigm, we interviewed seven participants (age range 12-19 years) diagnosed with chronic pain. Two frameworks for meaningful engagement of citizens in research and policy informed the interview guide. Data were analyzed inductively using content analysis approaches to examine patterns and develop themes. Results: The participants' perceptions were captured by the overarching theme of "understand me." Four subthemes elaborate on the relationship between the participants' experiences and how their lives could be enhanced through research and knowledge mobilization. In the subtheme "my unique pain experience," the participants help us understand them by chronicling the variation in presentation of their chronic pain. The subtheme "people don't know it's a thing" emphasizes that there is general misunderstanding of chronic pain by the public and in the participants' support systems. The first two subthemes influence the third, which describes how the pain "kind of stops you from living." The fourth subtheme, "knowledge offers hope," offers a solution to dismantling misunderstanding of youth living with chronic pain. Conclusion: Future work needs to focus on embedding health literacy and knowledge mobilization into health and education structures to promote developmentally relevant self-management skills.

Contexte: Il y a un manque perçu de ressources facilement disponibles pour soutenir les compétences d'auto-prise en charge chez les jeunes vivant avec de la douleur chronique. Les points de vue des jeunes sur les lacunes en matière d'information peuvent améliorer l'efficacité des ressources mises au point pour eux.Objectif: Le but de cette étude était d'explorer les perspectives des jeunes vivant avec de la douleur chronique sur les interactions entre leurs expériences de douleur, leurs ressources de douleur chronique et leurs recherches.Méthodes: À l'aide d'un paradigme d'interprétation, nous avons interrogé sept participants (âgés de 12 à 19 ans) qui avaient reçu un diagnostic de douleur chronique. Deux cadres pour une participation significative des citoyens à la recherche et aux politiques ont éclairé le guide d'entrevue. Les données ont été analysées par induction à l'aide d'approches d'analyse du contenu afin d'examiner les modèles et développer des thèmes.Résultats: Le thème général de « comprenez-moi ¼ reflète bien les perceptions des participants. Quatre sous-thèmes approfondissent la relation entre les expériences des participants et la façon dont leur vie pourrait être améliorée par la recherche et la mobilisation des connaissances. Dans le sous-thème « mon expérience de douleur unique ¼, les participants nous aident à les comprendre en racontant les variations dans la façon dont leur douleur chronique se présente. Le sous-thème « les gens ne savent pas que ça existe ¼ souligne qu'il y a une incompréhension générale de la douleur chronique par le public et dans les systèmes de soutien des participants. Les deux premiers sous-thèmes influencent le troisième, qui décrit comment la douleur « vous empêche de vivre en quelque sorte. ¼ Le quatrième sous-thème, « les connaissances apportent de l'espoir ¼, offre une solution pour démanteler l'incompréhension des jeunes vivant avec la douleur chronique.Conclusion: Les travaux futurs doivent se concentrer sur l'intégration de la littératie en santé et de la mobilisation des connaissances dans les structures de santé et d'éducation afin de promouvoir des compétences d'auto-prise en charge pertinentes sur le plan du développement.

Canadian Rheumatology Association Recommendations for the Screening, Monitoring, and Treatment of Juvenile Idiopathic Arthritis-Associated Uveitis.

OBJECTIVE: To develop Canadian recommendations for the screening, monitoring, and treatment of uveitis associated with juvenile idiopathic arthritis (JIA). METHODS: Recommendations were developed using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE)-ADOLOPMENT approach. A working group of 14 pediatric rheumatologists, 6 ophthalmologists, 2 methodologists, and 3 caregiver/patient representatives reviewed recent American College of Rheumatology (ACR)/Arthritis Foundation (AF) recommendations and worked in pairs to develop evidence-to-decision (EtD) tables. A survey to assess agreement and recommendations requiring group discussion was completed. EtD tables were presented, discussed, and voted upon at a virtual meeting, to produce the final recommendations. A health equity framework was applied to all aspects of the adolopment process including the EtD tables, survey responses, and virtual meeting discussion. RESULTS: The survey identified that 7 of the 19 recommendations required rigorous discussion. Seventy-five percent of working group members attended the virtual meeting to discuss controversial topics as they pertained to the Canadian environment, including timing to first eye exam, frequency of screening, escalation criteria for systemic and biologic therapy, and the role of nonbiologic therapies. Equity issues related to access to care and advanced therapeutics across Canadian provinces and territories were highlighted. Following the virtual meeting, 5 recommendations were adapted, 2 recommendations were removed, and 1 was developed de novo. CONCLUSION: Recommendations for JIA-associated uveitis were adapted to the Canadian context by a working group of pediatric rheumatologists, ophthalmologists with expertise in the management of uveitis, and parent/patient input, taking into consideration cost, equity, and access.

Chronic pain in children and adolescents in Manitoba: A retrospective chart review to inform the development of a provincial service for pediatric chronic pain.

Background: In the absence of an interdisciplinary service for pediatric chronic pain in Manitoba, pain management has been offered through a single provider outpatient setting with consultative services from physiotherapy, occupational therapy, and psychiatry since October 2015. Aims: The aim of this study was to characterize the patient population of this clinic to understand needs and inform future service development for pediatric chronic pain. Methods: Demographics and disease characteristics of all patients seen in this clinic between October 1, 2015, and February 28, 2019, were analyzed retrospectively from electronic medical records. Results: A total of 157 patients, mean age 13.1 (sd ±3.0) years, 75.2% female, with a median duration of pain of 20.5 (interquartile range [IQR] = 10.0-45.8) months at their first visit were included in the study. At baseline, 74.0% of patients experienced insomnia, 76.6% fatigue, 86.5% symptoms of anxiety, and 58.69% symptoms of depression; 80.1% showed withdrawal from physical activity, 67.1% missed school, and 10.2% reported opioid usage. Throughout their care in clinic, 83.4% of patients received physiotherapy, 17.8% occupational therapy, 49.7% mental health support, and 51.6% care from multiple services. The clinic experienced a significant increase in median referrals from 1.0 to 5.0 (IQR = 2.0-9.0) per month and wait time from 35.0 to 97.0 (IQR = 88.0-251.0) days during the observation period. Conclusions: Developing an interdisciplinary service for pediatric chronic pain will provide an opportunity to improve access, coordination, and comprehensiveness of care and to employ culturally sensitive services to improve care for children and youth living with chronic pain in Manitoba and possibly other jurisdictions with similar demographics and needs.

Contexte: En l'absence d'un service interdisciplinaire pour la douleur chronique pédiatrique au Manitoba, la prise en charge de la douleur est proposée par un seul prestataire ambulatoire qui offre des services consultatifs de physiothérapie, d'ergothérapie et de psychiatrie depuis octobre 2015.Buts: Le but de cette étude était de caractériser la population de patients de cette clinique pour comprendre les besoins et éclairer le développement futur de services pour la douleur chronique pédiatrique.Méthodes: Les données démographiques et les caractéristiques de la maladie de tous les patients vus dans cette clinique entre le 1er octobre 2015 et le 28 février 2019 ont été analysées rétrospectivement à partir des dossiers médicaux électroniques.Résultats: Un total de 157 patients, dont l'âge moyen était de 13,1 ans (é.-t. ±3,0) ans, 75,2 % de femmes, avec une durée de la douleur médiane de 20,5 mois (écart interquartile [IQR] = 10,0-45,8) à leur première visite étaient inclus dans l'étude. À l'inclusion, 74,0 % des patients présentaient de l'insomnie, 76,6 % de la fatigue, 86,5 % des symptômes d'anxiété et 58,69 % des symptômes de dépression ; 80,1 % montraient un retrait de l'activité physique, 67,1 % avaient manqué l'école et 10,2 % ont déclaré avoir consommé des opioïdes. Tout au long de leur traitement en clinique, 83,4 % des patients ont reçu de la physiothérapie, 17,8 % de l'ergothérapie, 49,7 % un traitement de soutien à la santé et 51,6 % des soins dispensés par de multiples services. La clinique a connu une augmentation significative des références médianes de 1,0 à 5,0 (IQR = 2,0-9,0) par mois et du temps d'attente de 35,0 à 97,0 (IQR = 88,0-251,0) pendant la période d'observation.Conclusions : La mise sur pied d'un service interdisciplinaire pour la douleur chronique pédiatrique permettra d'améliorer l'accès, la coordination et l'exhaustivité des soins de même que le recours à des services adaptés à la culture pour améliorer les soins aux enfants et aux jeunes souffrant de douleur chronique au Manitoba et possiblement dans d'autres provinces et territoires ayant des caractéristiques démographiques et des besoins semblables.

A Population-based Study of Grade 12 Academic Performance in Adolescents With Childhood-onset Chronic Rheumatic Diseases.

OBJECTIVE: The aims of this study were (1) to compare grade 12 standardized test results of patients diagnosed with childhood-onset chronic rheumatic diseases (ChildCRD) and unaffected peers; and (2) to identify factors associated with test results of patients with ChildCRD and unaffected peers. METHODS: This was a population-based retrospective cohort study. All patients with ChildCRD (juvenile arthritis and systemic autoimmune rheumatic diseases) from the only pediatric rheumatology center in Manitoba for birth cohorts January 1979 to December 1998 were linked to the provincial administrative databases containing records of healthcare use and education outcomes. Patients were matched by age, sex, and postal codes to their peers who did not have ChildCRD. The primary outcomes were the grade 12 Language Arts Achievement Index (LAI) and the Math Achievement Index (MAI) scores. ChildCRD, sociodemographic, and mental health factors were tested for their associations with LAI and MAI scores using multivariable linear regression. RESULTS: Five hundred and forty-one patients with ChildCRD were matched to 2713 unaffected peers. Patients with ChildCRD had lower LAI and MAI scores compared to their peers. More patients with ChildCRD failed or did not take the language arts (51% vs 41%, P < 0.001) and math (61% vs 55%, P = 0.02) tests. On multivariable analysis, ChildCRD, lower socioeconomic status, younger maternal age at first childbirth, family income assistance, involvement with child welfare services, and mental health morbidities (between ChildCRD diagnosis and standardized testing), were associated with worse LAI and MAI results. CONCLUSION: This population-based study showed that patients with ChildCRD performed less well than their peers on grade 12 standardized testing, independent of sociodemographic and mental health comorbidities.

Parent-Reported Medication Side Effects and Their Impact on Health-Related Quality of Life in Children With Juvenile Idiopathic Arthritis.

OBJECTIVE: To describe the frequency and severity of parent-reported medication side effects (SEs) in children with juvenile idiopathic arthritis (JIA) relative to physician-reported actionable adverse events (AEs), and to assess their impact on health-related quality of life (HRQoL). METHODS: Newly diagnosed JIA patients recruited between 2017 and 2019 to the Canadian Alliance of Pediatric Rheumatology Investigators (CAPRI) Registry were included. Parents reported presence and severity (0 = no problem, 10 = very severe) of medication SEs at every clinic visit. Physicians were asked to report any actionable AE. HRQoL was assessed using the Quality of My Life (QoML) questionnaire (0 = the worst, 10 = the best) and parent's global assessment (0 = very well, 10 = very poor). Analyses included proportion of visits with SEs or actionable AEs, cumulative incidence by Kaplan-Meier methods, and HRQoL impact measured with longitudinal mixed-effects models. RESULTS: SEs were reported at 371 of 884 (42%) visits (95% confidence interval [95% CI] 39, 45%) in 249 patients, with a median of 2 SEs per visit (interquartile range [IQR] 1-3), and median severity of 3 (IQR 1.5-5). Most SEs were gastrointestinal (32.5% of visits) or behavioral/psychiatric (22.4%). SE frequency was lowest with nonsteroidal antiinflammatory drugs alone (34.7%) and highest with prednisone and methotrexate combinations (66%). SE cumulative incidence was 67% (95% CI 59, 75) within 1 year of diagnosis, and 36% (95% CI 28, 44) for actionable AEs. Parent global and QoML scores were worse with SEs present; the impact persisted after adjusting for pain and number of active joints. CONCLUSION: Parents report that two-thirds of children with JIA experience SEs impacting their HRQoL within 1 year of diagnosis. SE mitigation strategies are needed in managing JIA.

Predicting Which Children with Juvenile Idiopathic Arthritis Will Not Attain Early Remission with Conventional Treatment: Results from the ReACCh-Out Cohort.

OBJECTIVE: To estimate the probability of early remission with conventional treatment for each child with juvenile idiopathic arthritis (JIA). Children with a low chance of remission may be candidates for initial treatment with biologics or triple disease-modifying antirheumatic drugs (DMARD). METHODS: We used data from 1074 subjects in the Research in Arthritis in Canadian Children emphasizing Outcomes (ReACCh-Out) cohort. The predicted outcome was clinically inactive disease for ≥ 6 months starting within 1 year of JIA diagnosis in patients who did not receive early biologic agents or triple DMARD. Models were developed in 200 random splits of 75% of the cohort and tested on the remaining 25% of subjects, calculating expected and observed frequencies of remission and c-index values. RESULTS: Our best Cox logistic model combining 18 clinical variables a median of 2 days after diagnosis had a c-index of 0.69 (95% CI 0.67-0.71), better than using JIA category alone (0.59, 95% CI 0.56-0.63). Children in the lowest probability decile had a 20% chance of remission and 21% attained remission; children in the highest decile had a 69% chance of remission and 73% attained remission. Compared to 5% of subjects identified by JIA category alone, the model identified 14% of subjects as low chance of remission (probability < 0.25), of whom 77% failed to attain remission. CONCLUSION: Although the model did not meet our a priori performance threshold (c-index > 0.70), it identified 3 times more subjects with low chance of remission than did JIA category alone, and it may serve as a benchmark for assessing value added by future laboratory/imaging biomarkers.

Lipopolysaccharides modulate allergen-specific immune regulation in a murine model of mucosal tolerance induction.

BACKGROUND: Farming has been widely reported to be associated with decreased risk of developing atopic disorders, but underlying immunomodulatory mechanisms are still not fully defined. We delineated T-cell functions after induction of mucosal tolerance in the context of intranasally delivered organic dust compounds, lipopolysaccharides (LPS). METHODS: BALB/c mice were pretreated intranasally with ovalbumin (OVA) with or without LPS (Escherichia coli) three times (days -21, -14, -7) prior to systemic OVA sensitization (days 1 and 14) and airway allergen challenges (days 28-30). CD4+ spleen T cells from pretreated and sensitized donors were characterized for cytokine function, and transferred into naive recipients prior to subsequent OVA sensitization and challenges. RESULTS: Intranasal OVA pretreatment suppressed Th2-mediated immune and inflammatory responses and enhanced frequency of regulatory T cells in OVA-sensitized and -challenged mice. Addition of LPS to OVA, but not LPS alone, inhibited development of allergen-induced sensitization and eosinophilic airway infiltration, and markedly enhanced allergen-specific IgG1 serum levels and frequencies of IL-10- and IFN-gamma-producing CD4+ T cells. Transfer of CD4+ spleen T cells from OVA-pretreated animals protected naive recipients against subsequent allergen sensitization and airway disease, whereas transfer from LPS/OVA-pretreated animals only protected against allergen sensitization. CONCLUSION: Microbial LPS modulated mucosal tolerance by inducing allergen-specific IgG1 production and distinct effector CD4+ T cells with a mixed regulatory/Th1 phenotype. Organic dust components such as LPS might therefore be important immune modulators in naturally occurring or preventive allergen-specific tolerance induction.

Primary prevention of allergic diseases: current concepts and mechanisms.

: Atopic diseases, the new "epidemic of the twenty-first century" and a central health problem of industrial nations, call for the development of innovative primary prevention strategies. The present review provides an overview of current experimental and immunomodulatory procedures and their underlying mechanisms.