Treating juvenile idiopathic arthritis to target: What is the optimal target definition to reach all goals?

In 2018, an international Task Force formulated recommendations for treating Juvenile Idiopathic Arthritis (JIA) to target. The Task Force has not yet resolved three issues. The first issue is the lack of a single "best" target. The Task Force decided not to recommend the use of a specific instrument to assess inactive disease or remission. Recent studies underscore the use of a broad target definition. The second issue is the basic assumption that a treatment aggressively aimed at the target will have 'domino effects' on other treatment goals as well. Thus far, this assumption was not confirmed for pain, fatigue and stiffness. The third issue is shared decision-making, and the role of individual patient targets. Nowadays, patients and parents should have a more active role in choosing targets and their personal treatment goals. In our department the electronic medical records have been restructured in such a way that the patient's personal treatment goals with a target date appears on the front page. The visualization of their specific personal goals helps us to have meaningful discussions on the individualized treatment strategy and to share decisions. In conclusion, a joint treat to target (T2T) strategy is a promising approach for JIA. The Task Force formulated valuable overarching principles and a first version of recommendations. However, implementation of T2T needs to capture more than just inactive disease. Patients and parents should have an active role in choosing personal targets as well

Feasibility of quantitative sensory testing in juvenile idiopathic arthritis

OBJECTIVE: Juvenile Idiopathic Arthritis (JIA) is a childhood-rheumatic disease with pain as a major early complaint, and in 10-17% pain remains a major symptom. Very few data exist on sensory threshold changes at the knee in JIA, a location in which inflammation often manifests. We determined whether JIA is associated with sensory threshold changes at the knee by using Quantitative Sensory Testing (QST) and established reference values at the knee of children. METHODS: Sixteen patients with JIA aged 9-18 years with one affected knee and a patient-reported pain by Visual Analog Scale (VAS) > 10 on a 0-100 scale, and 16 healthy controls completed the study and were included for the analysis. QST was assessed in compliance with the German Research Network on Neuropathic Pain (DFNS) standard. Disease severity was determined using Juvenile Disease Activity Score (JADAS. Perceived pain was assessed with a visual analogue scale(0-100). Feasibility of QST was tested in patients aged 6-9. RESULTS: Under the age of 9, QST testing showed not to be feasible in 3 out of 5 JIA patients. Patients with JIA aged 9 and older reported an average VAS pain score of 54.3. QST identified a significant reduction in pressure pain threshold (PPT) and increase in cold detection threshold (CDT) compared to healthy controls. PPT is reduced in both the affected and the unaffected knee, CDT is reduced in the unaffected knee, not the affected knee. CONCLUSION: In a Dutch cohort of Patients with JIA, QST is only feasible from 9 years and up. Also, sensory threshold changes at the knee are restricted to pressure pain and cold detection thresholds in Patients with JIA. PERSPECTIVE: This article shows that in a Dutch population, the extensive QST protocol is only feasible in the age group from 9 years and older, and a reduced set of QST tests containing at least pressure pain thresholds and cold detection thresholds could prove to be better suited to the pediatric setting with arthritis

Growth curves for mandibular range of motion and maximum voluntary bite force in healthy children

Mandibular range of motion and bite force are indispensable variables for the evaluation of mandibular function. There are a variety of medical and dental conditions that can negatively affect mandibular function. Values for mandibular range of motion (i.e., active and passive maximum interincisal mouth opening, protrusion, and laterotrusion) and anterior maximum voluntary bite force (AMVBF) in healthy children and adolescents can help in recognizing temporomandibular dysfunction. In this longitudinal study, 169 healthy children aged 6–18 years were included. They were examined at four time points over 1 year. Mixed model analysis was performed to produce growth curves of mandibular range of motion and AMVBF. Average active maximum interincisal mouth opening was significantly higher in boys with 50.0 mm compared to 47.8 mm in girls. Boys also had a significantly higher AMVBF than girls with an average of 169.0 N versus 140.0 N, respectively. Growth curves of active and passive maximum interincisal mouth opening showed an increase with age, albeit levelling off through puberty. The growth curves of AMVBF in girls reach a plateau phase at ages 12–14 years, after which the curve descends; in boys, the AMVBF tended to increase up to 18 years of age, although a slow-down after 14 years of age was noted

Pharmacological conditioning for juvenile idiopathic arthritis:a potential solution to reduce methotrexate intolerance

Background: Methotrexate (MTX) therapy has proven to be a successful and safe treatment for Juvenile Idiopathic Arthritis (JIA). Despite the high efficacy rates of MTX, treatment outcomes are often complicated by burdensome gastro-intestinal side effects. Intolerance rates for MTX in children are high (approximately 50%) and thus far no conclusive effective treatment strategies to control for side effects have been found. To address this need, this article proposes an innovative research approach based on pharmacological conditioning, to reduce MTX intolerance. Presentation of the hypothesis: A collaboration between medical psychologists, pediatric rheumatologists, pharmacologists and patient groups was set up to develop an innovative research design that may be implemented to study potential improved control of side effects in JIA, by making use of the psychobiological principles of pharmacological conditioning. In pharmacological conditioning designs, learned positive associations from drug therapies (conditioning effects) are integrated in regular treatment regimens to maximize treatment outcomes. Medication regimens with immunosuppressant drugs that made use of pharmacological conditioning principles have been shown to lead to optimized therapeutic effects with reduced drug dosing, which might ultimately cause a reduction in side effects. Testing the hypothesis: This research design is tailored to serve the needs of the JIA patient group. We developed a research design in collaboration with an interdisciplinary research group consisting of patient representatives, pediatric rheumatologists, pharmacologists, and medical psychologists. Implications of the hypothesis: Based on previous experimental and clinical findings of pharmacological conditioning with immune responses, we propose that the JIA patient group is particularly suited to benefit from a pharmacological conditioning design. Moreover, findings from this study may potentially also be promising for other patient groups that endure long-lasting drug therapies

Genomic Health Literacy Interventions in Pediatrics:Scoping Review

BACKGROUND: The emergence of genetic and genomic sequencing approaches for pediatric patients has raised questions about the genomic health literacy levels, attitudes toward receiving genomic information, and use of this information to inform treatment decisions by pediatric patients and their parents. However, the methods to educate pediatric patients and their parents about genomic concepts through digital health interventions have not been well-established. OBJECTIVE: The primary objective of this scoping review is to investigate the current levels of genomic health literacy and the attitudes toward receiving genomic information among pediatric patients and their parents. The secondary aim is to investigate patient education interventions that aim to measure and increase genomic health literacy among pediatric patients and their parents. The findings from this review will be used to inform future digital health interventions for patient education. METHODS: A scoping review using PRISMA-ScR (Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews) guidelines and protocols was completed using the following databases: MEDLINE, Embase, CINAHL, and Scopus. Our search strategy included genomic information inclusive of all genetic and genomic terms, pediatrics, and patient education. Inclusion criteria included the following: the study included genetic, genomic, or a combination of genetic and genomic information; the study population was pediatric (children and adolescents <18 years) and parents of patients with pediatric illnesses or only parents of patients with pediatric illnesses; the study included an assessment of the knowledge, attitudes, and intervention regarding genomic information; the study was conducted in the last 12 years between 2008 and 2020; and the study was in the English language. Descriptive data regarding study design, methodology, disease population, and key findings were extracted. All the findings were collated, categorized, and reported thematically. RESULTS: Of the 4618 studies, 14 studies (n=6, 43% qualitative, n=6, 43% mixed methods, and n=2, 14% quantitative) were included. Key findings were based on the following 6 themes: knowledge of genomic concepts, use of the internet and social media for genomic information, use of genomic information for decision-making, hopes and attitudes toward receiving genomic information, experiences with genetic counseling, and interventions to improve genomic knowledge. CONCLUSIONS: This review identified that older age is related to the capacity of understanding genomic concepts, increased genomic health literacy levels, and the perceived ability to participate in decision-making related to genomic information. In addition, internet-searching plays a major role in obtaining genomic information and filling gaps in communication with health care providers. However, little is known about the capacity of pediatric patients and their parents to understand genomic information and make informed decisions based on the genomic information obtained. More research is required to inform digital health interventions and to leverage the leading best practices to educate these genomic concepts

Cross-Cultural Adaptation and Validation of the Methotrexate Intolerance Severity Score Questionnaire in Portuguese (Brazil) for Children and Adolescents with Juvenile Idiopathic Arthritis

The Methotrexate (MTX) Intolerance Severity Score (MISS) questionnaire has been developed to identify MTX adverse events in juvenile idiopathic arthritis (JIA). The objective of this study was to translate and validate MISS into Brazilian Portuguese for children and adolescents. The MISS was translated into Portuguese following the standardized guidelines. We analyzed the following psychometric properties: acceptability, internal consistency, test–retest reproducibility, relative–child reliability, and external criterion and discriminant validity. We included 138 JIA patients (age: 8–18 years) and 108 relatives who took less than 5 min to answer MISS. Reproducibility tested after 15 days was good, with a kappa > 0.76. We observed good internal consistency (Cronbach’s coefficient 0.75–0.87 (patients) and 0.75–0.79 (relatives)). Reliability between patients and relatives was good except for stomachache and restlessness. Cut-off points of 5 and 6 had good sensitivity (84 and 71, respectively) and specificity (80 and 87, respectively). Using a cut-off value of 6, we observed 86 (62.3%) MTX-intolerant patients. In conclusion, MISS is a viable and practical tool for routine clinical care to identify MTX intolerance in JIA. Parents do not easily identify stomachache and restlessness as adverse MTX events

A diagnostic prediction model for separating juvenile idiopathic arthritis and chronic musculoskeletal pain syndrome

Objective: To develop and validate a diagnostic prediction model that can distinguish between juvenile idiopathic arthritis (JIA) and chronic musculoskeletal pain syndrome (CMPS) based on patient-reported outcomes. Study design: This retrospective cohort study evaluated whether the Juvenile Arthritis Multidimensional Assessment Report (JAMAR) performs well in distinguishing JIA from CMPS. We analyzed JAMARs completed by 287 patients at their first visit to the pediatric rheumatology department of Wilhelmina Children's Hospital in Utrecht, The Netherlands. Relevant JAMAR items for predicting a diagnosis of JIA were selected in a penalized multivariable model suitable for clinical application. The model was subsequently validated with new data from the same center. Results: A total of 196 JAMARs (97 JIA, 99 CMPS) were collected in the model development data, and 91 JAMARs (48 JIA, 43 CMPS) were collected in the validation data. Variables in the prediction model that were strongest associated with a diagnosis of JIA instead of CMPS were asymmetric pain/swelling in the shoulder (OR, 2.34), difficulty with self-care (OR, 2.41), skin rash (OR, 2.07), and asymmetric/pain swelling in the knee (OR, 2.29). Calibration and discrimination (area under the receiver operating characteristic curve, 0.83; 95% CI, 0.74-0.92) of the model in the validation data were good. Conclusions: Several items from the JAMAR questionnaire can potentially distinguish JIA from CMPS in patients with corresponding symptoms. We present an easy-to-use, adjusted, and validated model to separate these 2 diagnoses early at presentation based on patient-reported outcomes to facilitate proper referral and treatment