Alan M. Rosenberg

Digital health (DH) technologies have the potential to benefit pediatric patients with rheumatic diseases and their caregivers. Digital health literacy (DHL) refers to the knowledge and skills necessary to use technology and the internet to manage and communicate about health. The aim of this scoping review is to identify facilitators of and barriers to DHL and map them to the Capability, Opportunity, and Motivation Model of Behavior (COM-B Model) for children and adolescents with rheumatic diseases and their primary caregivers. We searched MEDLINE, CINAHL, Embase, Web of Science, and ProQuest for English full-text primary research studies. Facilitators of and barriers to DHL identified were codified and mapped to the COM-B Model. This review adhered to the JBI scoping review framework and conformed to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA)-Scoping Review guidelines. Of the 5789 unique records, 44 met inclusion criteria. All the included studies did not explicitly address the concept and impact of DHL. However, the studies identified promoting and detracting factors that matched the definition of DHL. Thus, these were coded as facilitators of and barriers to DHL. The COM-B Model domain of psychological capability emerged as a major determinant of DHL. The COM-B Model domain of psychological capability emerged as a prominent source of facilitators of and barriers to DHL. The design, function, language, and presentation of DH crafted to meet the developmental and educational needs of the user were essential to improving DHL. Likewise, providers fostering quality communication and answering medical and technical questions arising from DH use fostered DHL in the domain of physical opportunity. Addressing DHL requires consideration across clinical, administrative, design, and research contexts. Recognizing low DHL and enacting educational interventions are essential to empowering digital health users. Trial Registration Open Science Framework ( https://osf.io/g4jbh/ ).

Background/Objectives: Online health information (OHI) is used by adolescents and caregivers to manage pediatric rheumatic diseases (PRDs). Little is known about the lived experiences of this group as they navigate complex, evolving online healthcare information and services. This study aimed to explore the lived experiences and indicators of digital health literacy (DHL) among adolescents with PRD and caregivers of children and adolescents with PRD through their use of OHI to learn about and manage their disease. Methods: Qualitative interviews using Interpretive Description methodology was utilized. Adolescent and caregiver participants were recruited using purposeful sampling from one rheumatology clinic in Saskatchewan, Canada. After completing a pre-interview questionnaire, one-on-one semi-structured telephone interviews were completed, audio-recorded, transcribed verbatim, and analyzed using constant comparative analysis. Results: A total of 10 caregivers and 7 adolescents completed the interviews. Three key themes emerged: (1) OHI offers knowledge without imposing on PRD practitioners. Participants were motivated to use OHI for symptom management, reassurance, and medication administration. (2) Participants had difficulty finding OHI, resulting from their search strategies, desire for answers to complex problems, lack of information for novel biologic medications, the absence of adolescent-focused OHI, and confusion around pediatric to adult disease names. (3) Although aware of misinformation, participants discussed and demonstrated inadequate appraisal of OHI. Conclusions: Participants relied on inappropriate indicators of medical accuracy and misplaced trust in OHI sources, leading to exposure to misinformation. Proactively addressing these concerns, including OHI prescriptions, fostering independent OHI appraisal, and development of age-appropriate OHI, may improve DHL and aid PRD management.

Juvenile idiopathic arthritis (JIA), the most common class of pediatric rheumatic diseases, can lead to joint damage and extra-articular features including uveitis. Early treatment can improve functional outcomes; but many patients do not respond to first-line treatments. We present a JIA Immunochip-based association analysis of rheumatoid factor-negative polyarticular JIA and oligoarticular JIA. This study spans 3,939 cases and 14,412 controls, including 1,123 cases and 1,356 controls not previously analyzed. We identify 41 (14 novel) JIA risk regions and report a JIA polygenic risk score that also associates with age of onset. Functional mechanisms presented include: a novel interaction between HLA-A*02:01 and ERAP2 , cluster-based approach for functional amino acid discovery within HLA-DRB1, and sequence-dependent DNA topology for variant prioritization. We present a comprehensive list of curated gene-drug/small molecule interactions for clinically focused studies. These findings provide a deepened understanding of the genetics of JIA and potential mechanisms to inform precision medicine.

Gene sets are collections of genes that share a common biological function, process, or component and are widely used to interpret genomic data. Databases containing these gene sets support many analytical methods, including gene set analysis and phenotype-based gene prioritization, whose results depend on gene set quality. Despite extensive literature and genetic data, existing resources often lack sufficient biological context. Current curation relies on labour‑intensive expert review and automated methods that are not context‑aware, leaving an opportunity to use publicly available literature to construct more precise gene sets. With advances in natural language processing, particularly large language models (LLMs), this task can be performed more efficiently. In this work, we systematically evaluate open‑source LLMs (Llama 3.1, DeepSeek-R1, and Qwen 3) for reconstructing gene sets from PubMed abstracts. Our approach consists of two pipelines. One verifies the inclusion of genes in a gene set by requiring evidence in abstracts for the gene-phenotype association, and the other scans abstracts to identify genes not already included for potential addition. We compare direct prompting with retrieval‑augmented processing, evaluate the three individual models, and examine a majority‑vote consensus. Using the Human Phenotype Ontology (HPO) as a reference, we compute per‑phenotype precision, recall, and F1‑score for each construction. We further assess the biological validity of newly added genes through targeted literature review and analyze lost HPO genes to distinguish likely noisy annotations from retrieval or reasoning failures. Our results show that the best open‑source configurations achieve high precision while recovering a substantial fraction of HPO genes, and that many newly added genes show strong phenotype‑specific support in the literature. Together, these findings suggest that open‑source LLMs, combined with retrieval and voting, offer a practical and transparent way to curate context-rich phenotype-gene sets.

Objective: To assess changes in juvenile idiopathic arthritis (JIA) treatments and outcomes in Canada, comparing 2005–2010 and 2017–2021 inception cohorts. Methods: Patients enrolled within three months of diagnosis in the Research in Arthritis in Canadian Children Emphasizing Outcomes (ReACCh-Out) and the Canadian Alliance of Pediatric Rheumatology Investigators Registry (CAPRI) cohorts were included. Cumulative incidences of drug starts and outcome attainment within 70 weeks of diagnosis were compared with Kaplan–Meier survival analysis and multivariable Cox regression. Results: The 2005–2010 and 2017–2021 cohorts included 1128 and 721 patients, respectively. JIA category distribution and baseline clinical juvenile idiopathic arthritis disease activity (cJADAS10) scores at enrolment were comparable. By 70 weeks, 6% of patients (95% CI 5, 7) in the 2005–2010 and 26% (23, 30) in the 2017–2021 cohort had started a biologic DMARD (bDMARD), and 43% (40, 47) and 60% (56, 64) had started a conventional DMARD (cDMARD), respectively. Outcome attainment was 64% (61, 67) and 83% (80, 86) for inactive disease (Wallace criteria), 69% (66, 72) and 84% (81, 87) for minimally active disease (cJADAS10 criteria), 57% (54, 61) and 63% (59, 68) for pain control (<1/10), and 52% (47, 56) and 54% (48, 60) for good health-related quality of life (≥9/10). Conclusion: Although baseline disease characteristics were comparable in the 2005–2010 and 2017–2021 cohorts, cDMARD and bDMARD use increased with a concurrent increase in minimally active and inactive disease. Improvements in parent and patient-reported outcomes were smaller than improvements in disease activity.

Chronic asymptomatic and acute symptomatic anterior uveitis are forms of ocular inflammation associated with juvenile idiopathic arthritis (JIA) Chronic JIA-associated uveitis is characterized by young age of onset, female predilection, oligoarthritis, and antinuclear antibody (ANA) positivity. Acute JIA-associated uveitis predominantly affects older male juveniles who also develop enthesitis. A type I collagen-derived peptide (melanin-associated antigen [MAA]) induces anterior uveitis in rodents. In this study, we evaluated MAA-induced uveitis in rats as a potential model for JIA-uveitis. We characterized MAA-induced uveitis by assessing its relationship to age and sex; tracking the occurrence of arthritis, enthesitis, and ANA positivity; and measuring vitreous fluid inflammatory biomarkers. Juvenile and adult and male and female Lewis rats (Rattus norvegicus) were inoculated with MAA. Slit-lamp biomicroscopy, indirect ophthalmoscopy, and joint examinations were performed 3 times weekly. Rats were euthanized at 4 wk after MAA inoculation, and plasma ANA testing, vitreous inflammatory biomarker assays, and globe histopathology assessments were conducted. Uveitis, arthritis, ANA status, levels of inflammatory biomarkers, histopathology, and joint tomographic images were assessed in relation to age and sex and compared with nonuveitic controls. All MAA-immunized rats developed uveitis characterized by anterior chamber fibrin, iridal vessel dilation, and miosis, and uveal and choroidal lymphocytic infiltration. Levels of the vitreous fluid biomarker CCL5 were higher in uveitic rats compared with control rats. Time to uveitis onset, clinical uveitis scores, and biomarker levels did not differ based on age or sex. None of the MAA-exposed rats had arthritis, enthesitis, or ANA. None of the rats inoculated with MAA that had been treated with matrix metallopeptidase 1 had clinical, histologic, or immunohistochemical evidence of ocular inflammation. In contrast to JIA-associated uveitis in humans, MAA-induced uveitis in rats is not associated with age or sex predilections and MAA is not arthritogenic.

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 EtD tables, survey responses, and virtual meeting discussion. Results The survey identified that 7 of the nineteen 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 non-biologic 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 utilizing lenses for cost, equity, and access.

Background: Physical activity (PA) patterns in children with juvenile idiopathic arthritis (JIA) over time are not well described. The aim of this study was to describe associations of physical activity (PA) with disease activity, function, pain, and psychosocial stress in the 2 years following diagnosis in an inception cohort of children with juvenile idiopathic arthritis (JIA). Methods: In 82 children with newly diagnosed JIA, PA levels, prospectively determined at enrollment, 12 and 24 months using the Physical Activity Questionnaire for Children (PAQ-C) and Adolescents (PAQ-A) raw scores, were evaluated in relation to disease activity as reflected by arthritis activity (Juvenile Arthritis Disease Activity Score (JADAS-71)), function, pain, and psychosocial stresses using a linear mixed model approach. Results in the JIA cohort were compared to normative Pediatric Bone Mineral Accrual Study data derived from healthy children using z-scores. Results: At enrollment, PA z-score levels of study participants were lower than those in the normative population (median z-score − 0.356; p = 0.005). At enrollment, PA raw scores were negatively associated with the psychosocial domain of the Juvenile Arthritis Quality of Life Questionnaire (r = − 0.251; p = 0.023). There was a significant decline in PAQ-C/A raw scores from baseline (median and IQR: 2.6, 1.4–3.1) to 24 months (median and IQR: 2.1, 1.4–2.7; p = 0.003). The linear mixed-effect model showed that PAQ-C/A raw scores in children with JIA decreased as age, disease duration, and ESR increased. The PAQ-C/A raw scores of the participants was also negatively influenced by an increase in disease activity as measured by the JADAS-71 (p < 0.001). Conclusion: Canadian children with newly diagnosed JIA have lower PA levels than healthy children. The decline in PA levels over time was associated with disease activity and higher disease-specific psychosocial stress.