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Clinical Ophthalmology (Auckland, N.Z.) 2024Understanding sociodemographic factors associated with poor visual outcomes in children with juvenile idiopathic arthritis-associated uveitis may help inform practice...
PURPOSE
Understanding sociodemographic factors associated with poor visual outcomes in children with juvenile idiopathic arthritis-associated uveitis may help inform practice patterns.
PATIENTS AND METHODS
Retrospective cohort study on patients <18 years old who were diagnosed with both juvenile idiopathic arthritis and uveitis based on International Classification of Diseases tenth edition codes in the Intelligent Research in Sight Registry through December 2020. Surgical history was extracted using current procedural terminology codes. The primary outcome was incidence of blindness (20/200 or worse) in at least one eye in association with sociodemographic factors. Secondary outcomes included cataract and glaucoma surgery following uveitis diagnosis. Hazard ratios were calculated using multivariable-adjusted Cox proportional hazards models.
RESULTS
Median age of juvenile idiopathic arthritis-associated uveitis diagnosis was 11 (Interquartile Range: 8 to 15). In the Cox models adjusting for sociodemographic and insurance factors, the hazard ratios of best corrected visual acuity 20/200 or worse were higher in males compared to females (HR 2.15; 95% CI: 1.45-3.18), in Black or African American patients compared to White patients (2.54; 1.44-4.48), and in Medicaid-insured patients compared to commercially-insured patients (2.23; 1.48-3.37).
CONCLUSION
Sociodemographic factors and insurance coverage were associated with varying levels of risk for poor visual outcomes in children with juvenile idiopathic arthritis-associated uveitis.
PubMed: 38741584
DOI: 10.2147/OPTH.S456252 -
Pediatric Rheumatology Online Journal Mar 2024Juvenile idiopathic arthritis (JIA) is a type of chronic childhood arthritis with complex pathogenesis. Immunological studies have shown that JIA is an acquired...
BACKGROUND
Juvenile idiopathic arthritis (JIA) is a type of chronic childhood arthritis with complex pathogenesis. Immunological studies have shown that JIA is an acquired self-inflammatory disease, involving a variety of immune cells, and it is also affected by genetic and environmental susceptibility. However, the precise causative relationship between the phenotype of immune cells and JIA remains unclear to date. The objective of our study is to approach this inquiry from a genetic perspective, employing a method of genetic association analysis to ascertain the causal relationship between immune phenotypes and the onset of JIA.
METHODS
In this study, a two-sample Mendelian randomization (MR) analysis was used to select single nucleotide polymorphisms (SNPs) significantly associated with immune cells as instrumental variables to analyze the bidirectional causal relationship between 731 immune cells and JIA. There were four types of immune features (median fluorescence intensity (MFI), relative cellular (RC), absolute cellular (AC), and morphological parameters (MP)). Finally, the heterogeneity and horizontal reproducibility of the results were verified by sensitivity analysis, which ensured more robust results.
RESULTS
We found that CD3 on CM CD8br was causally associated with JIA at the level of 0.05 significant difference (95% CI = 0.630 ~ 0.847, P = 3.33 × 10, P = 0.024). At the significance level of 0.20, two immunophenotypes were causally associated with JIA, namely: HLA DR on CD14+ CD16- monocyte (95% CI = 0.633 ~ 0.884, P = 6.83 × 10 P = 0.16) and HLA DR on CD14+ monocyte (95% CI = 0.627 ~ 0.882, P = 6.9 × 10, P = 0.16).
CONCLUSION
Our study assessed the causal effect of immune cells on JIA from a genetic perspective. These findings emphasize the complex and important role of immune cells in the pathogenesis of JIA and lay a foundation for further study of the pathogenesis of JIA.
Topics: Humans; Child; Arthritis, Juvenile; Genotype; Genetic Predisposition to Disease; Reproducibility of Results; HLA-DR Antigens; Polymorphism, Single Nucleotide; Genome-Wide Association Study
PubMed: 38459548
DOI: 10.1186/s12969-024-00970-8 -
Scientific Reports Jan 2024Several observational studies have revealed an association between autoimmune diseases (AIDs) and colorectal cancer (CRC), although their causal association remained...
Several observational studies have revealed an association between autoimmune diseases (AIDs) and colorectal cancer (CRC), although their causal association remained controversial. Therefore, our study used a two-sample Mendelian randomization (MR) analysis to verify the causal association between AIDs and CRC. We employed three common MR approaches, including inverse variance weighted (IVW), weighted median, and MR-Egger methods, to assess the causal association between type 1 diabetes (T1D), systemic lupus erythematosus, rheumatoid arthritis, psoriasis, multiple sclerosis, juvenile idiopathic arthritis, celiac disease, and primary sclerosing cholangitis (PSC) and CRC. The reverse MR analysis was performed to assess the possibility of reverse causation. To evaluate the validity of the analysis, we also performed sensitivity analysis, such as the heterogeneity test, the horizontal pleiotropy test, and the leave-one-out sensitivity analysis, and validated the results in the validation cohort. Our results showed that genetically predicted T1D was nominally associated with a lower risk of CRC (IVW OR = 0.965, 95% CI = 0.939-0.992, P = 0.012). However, genetic susceptibility to psoriasis nominally increased the risk of CRC (IVW OR = 1.026, 95% CI = 1.002-1.050, P = 0.037). Genetically predicted PSC had a significant causal effect on the increasing risk of CRC (IVW OR = 1.038, 95% CI = 1.016-1.060, P = 5.85 × 10). Furthermore, the MR analysis between PSC and the CRC validation cohort indicated consistent results. We found no causal association between genetically predicted other five AIDs and CRC (P > 0.05). The results of reverse MR analysis showed that genetically predicted CRC had no causal effect on T1D, psoriasis, and PSC (P > 0.05). The sensitivity analysis demonstrated that the results of the MR analysis were reliable. Our findings help to understand the causal association between AIDs and CRC, which deserves further investigation.
Topics: Humans; Diabetes Mellitus, Type 1; Mendelian Randomization Analysis; Arthritis, Juvenile; Psoriasis; Colorectal Neoplasms
PubMed: 38238429
DOI: 10.1038/s41598-024-51903-0 -
Pediatric Rheumatology Online Journal Nov 2023Juvenile Idiopathic Arthritis (JIA) is the most common form of childhood inflammatory arthritis. The disease burden of JIA is substantial as patients require specialized... (Review)
Review
Reporting of determinants of health inequities and participant characteristics in randomized controlled trials of juvenile idiopathic arthritis in Canada: a scoping review.
BACKGROUND
Juvenile Idiopathic Arthritis (JIA) is the most common form of childhood inflammatory arthritis. The disease burden of JIA is substantial as patients require specialized medical practitioners for diagnosis and chronic treatments that are both costly and time intensive. Discrepancies in access to care due to health inequities such as socioeconomic status or geographic location may lead to vastly different health outcomes. As research informs advances in care, is important to consider inclusion and diversity in JIA research.
METHODS
We reviewed and synthesized randomized controlled trials for juvenile idiopathic arthritis, the most common type of arthritis among children and adolescents, in Canada with the aim of characterizing participants and identifying how determinants of health inequities are reported. To do so, we searched Medline (1990 to July 2022), Embase (1990 to July 2022), and CENTRAL (inception to July 2022) for articles meeting all of the following criteria: Canadian randomized controlled trials evaluating pharmacological or non-pharmacological interventions on juvenile idiopathic arthritis populations. Data extraction was guided by the Campbell and Cochrane Equity Methods Group's PROGRESS-Plus framework on determinants that lead to health inequities (e.g., Place of residence; Race; Occupation; Gender/Sex; Religion; Education; Socioeconomic status; and Social capital).
RESULTS
Of 4,074 unique records, 5 were deemed eligible for inclusion. From these determinants of health inequities, Gender/Sex and Age were the only that were reported in all studies with most participants being female and 12.6 years old on average. In addition, Race, Socioeconomic status, Education and Features of relationships were each reported once in three different studies. Lastly, Place of residence, Occupation, Religion, Social Capital and Time-dependent relationships were not reported at all.
CONCLUSIONS
This scoping review suggests limited reporting on determinants of health inequities in randomized controlled trials for JIA in Canada and a need for a reporting framework that reflects typical characteristics of juvenile patient populations.
Topics: Child; Adolescent; Humans; Female; Male; Arthritis, Juvenile; Canada; Randomized Controlled Trials as Topic; Health Inequities
PubMed: 37932754
DOI: 10.1186/s12969-023-00917-5 -
Rheumatology International Aug 2023Depression is a serious disorder disproportionately affecting people with chronic diseases, yet, to date is rarely recognized comorbidity in pediatric rheumatology...
Depression is a serious disorder disproportionately affecting people with chronic diseases, yet, to date is rarely recognized comorbidity in pediatric rheumatology clinical routine care. The aim of this study was to investigate the prevalence of depressive symptoms and depression in children with Juvenile idiopathic arthritis (JIA) and to identify associations to risk factors. Depressive symptoms were assessed using the Beck's Depression Inventory (BDI)-Fast Screen Questionnaire validated for ages 13 and older and confirmed by the BDI or Hamilton Depression Scale. A cross-sectional analysis of 148 patients attending the rheumatology outpatient clinic of the Asklepios Children's Hospital Sankt Augustin between January 2018 and May 2019 was performed. Possible associations between routinely assessed parameters of disease activity and treatment were analysed. 148 JIA patients (71.5% female), median age 14.7 years, were included. The prevalence for depressive symptoms was 13% and for depression 9.5%, of which 71.4% were newly identified with depression. Significant associations with depressive symptoms included rheumatoid factor negative polyarthritis, higher pain scores, functional limitations, higher disease activity, decreased general well-being, higher number of medications taken and not being in remission. In addition, poor treatment response (persistent pain despite therapy) and failure to achieve minimal activity/remission of disease despite intensified therapy with biologics correlated significantly with depressive symptoms. Depressive symptoms are an important comorbidity in JIA. Early recognition and treatment of psychological distress is essential to prevent deterioration in quality of life and long-term prognosis. Consequently, treat-to-target principles should include mental health as a therapeutic goal.
Topics: Humans; Child; Female; Adolescent; Male; Arthritis, Juvenile; Depression; Quality of Life; Prevalence; Cross-Sectional Studies; Risk Factors; Pain
PubMed: 37039854
DOI: 10.1007/s00296-023-05323-4 -
Journal of Health Economics and... 2023Juvenile idiopathic arthritis (JIA) is the most frequent chronic rheumatic disease in children. If inflammation is not adequately treated, joint damage, long-term...
Juvenile idiopathic arthritis (JIA) is the most frequent chronic rheumatic disease in children. If inflammation is not adequately treated, joint damage, long-term disability, and active disease during adulthood can occur. Identifying and implementing early and adequate therapy are critical for improving clinical outcomes. The burden of JIA on affected children, their families, and the healthcare system in Spain has not been adequately assessed. The greatest contribution to direct costs is medication, but other expenses contribute to the consumption of resources, negatively impacting healthcare cost and the economic conditions of affected families. To assess the direct healthcare, indirect resource utilization, and associated cost of moderate-to-severe JIA in children in routine clinical practice in Spain. Children were enrolled in this 24-month observational, multicentric, cross-sectional, retrospective study (N = 107) if they had been treated with biologic disease-modifying anti-rheumatic drugs (bDMARDs), had participated in a previous study (ITACA), and continued to be followed up at pediatric rheumatology units at 3 tertiary Spanish hospitals. Direct costs included medication, specialist and primary care visits, hospitalizations, emergency visits or consultations, surgeries, physiotherapy, and tests. Indirect costs included hospital travel expenses and loss of caregiver working hours. Unitary costs were obtained from official sources (€, 2020). Overall, children had inactive disease/low disease activity according to JADAS-71 score and very low functional disability as measured by Childhood Health Assessment Questionnaire score. Up to 94.4% of children received treatment, mainly with bDMARDs as monotherapy (84.5%). Among anti-TNFα treatments, adalimumab (47.4%) and etanercept (40.2%) were used in similar proportions. Annual mean (SD) total JIA cost was €7516.40 (€5627.30). Average cost of pharmacological treatment was €3021.80 (€3956.20), mainly due to biologic therapy €2789.00 (€3399.80). Direct annual cost (excluding treatments) was €3654.60 (€3899.00). Indirect JIA cost per family was €747.20 (€1452.80). JIA causes significant costs to the Spanish healthcare system and affected families. Public costs are partly due to the high cost of biologic treatments, which nevertheless remain an effective long-term treatment, maintaining inactive disease/low disease activity state; a very low functional disability score; and a good quality of life.
PubMed: 38145114
DOI: 10.36469/001c.85088 -
BMJ Open Dec 2023External control arms (ECAs) provide useful comparisons in clinical trials when randomised control arms are limited or not feasible. We conducted a systematic review to...
OBJECTIVES
External control arms (ECAs) provide useful comparisons in clinical trials when randomised control arms are limited or not feasible. We conducted a systematic review to summarise applications of ECAs in trials of immune-mediated inflammatory diseases (IMIDs).
DESIGN
Systematic review with an appraisal of ECA source quality rated across five domains (data collection, study populations, outcome definitions, reliability and comprehensiveness of the dataset, and other potential limitations) as high, low or unclear quality.
DATA SOURCES
Embase, Medline and Cochrane Central Register of Controlled Trial were searched through to 12 September 2023.
ELIGIBILITY CRITERIA
Eligible studies were single-arm or randomised controlled trials (RCTs) of inflammatory bowel disease, pouchitis, rheumatoid arthritis, juvenile idiopathic arthritis, ankylosing spondylitis, psoriatic arthritis, psoriasis and atopic dermatitis in which an ECA was used as the comparator.
DATA EXTRACTION AND SYNTHESIS
Two authors independently screened the search results in duplicate. The characteristics of included studies, external data source(s), outcomes and statistical methods were recorded, and the quality of the ECA data source was assessed by two independent authors.
RESULTS
Forty-three studies met the inclusion criteria (inflammatory bowel disease: 16, pouchitis: 1, rheumatoid arthritis: 12, juvenile idiopathic arthritis: 1, ankylosing spondylitis: 5, psoriasis: 3, multiple indications: 4). The majority of these trials were single-arm (33/43) and enrolled adult patients (34/43). All included studies used a historical control rather than a contemporaneous ECA. In RCTs, ECAs were most often derived from the placebo arm of another RCT (6/10). In single-arm trials, historical case series were the most common ECA source (19/33). Most studies (31/43) did not employ a statistical approach to generate the ECA from historical data.
CONCLUSIONS
Standardised ECA methodology and reporting conventions are lacking for IMIDs trials. The establishment of ECA reporting guidelines may enhance the rigour and transparency of future research.
Topics: Adult; Humans; Spondylitis, Ankylosing; Pouchitis; Arthritis, Rheumatoid; Psoriasis; Inflammatory Bowel Diseases; Immunomodulating Agents
PubMed: 38070932
DOI: 10.1136/bmjopen-2023-076677 -
Current Rheumatology Reports Dec 2023This review aims to critically evaluate the potential benefit of either oral or subcutaneous administration of methotrexate (MTX) in various immune-mediated inflammatory... (Review)
Review
PURPOSE
This review aims to critically evaluate the potential benefit of either oral or subcutaneous administration of methotrexate (MTX) in various immune-mediated inflammatory disorders (IMIDs) through analysis of efficacy, toxicity, pharmacokinetics and pharmacodynamics of both administration routes.
RECENT FINDINGS
Recent studies comparing the efficacy of oral versus subcutaneous MTX administration in IMIDs have revealed contradicting results. Some reported higher efficacy with subcutaneous administration, while others found no significant difference. Regarding toxicity, some studies have challenged the notion that subcutaneous administration is better tolerated than oral administration, while others have supported this. Pharmacokinetic studies suggest higher plasma bioavailability and increased accumulation of MTX-polyglutamates (MTX-PGs) in red blood cells (RBCs) with subcutaneous administration during the initial treatment phase. However, after several months, similar intracellular drug levels are observed with both administration routes. There is no conclusive evidence supporting the superiority of either oral or subcutaneous MTX administration in terms of efficacy and adverse events in IMIDs. Subcutaneous administration leads to higher plasma bioavailability and initial accumulation of MTX-PGs in RBCs, but the difference seems to disappear over time. Given the variable findings, the choice of administration route may be based on shared decision-making, offering patients the option of either oral or subcutaneous administration of MTX based on individual preferences and tolerability. Further research is needed to better understand the impact of MTX-PGs in various blood cells and TDM on treatment response and adherence to MTX therapy.
Topics: Humans; Methotrexate; Antirheumatic Agents; Injections, Subcutaneous; Administration, Oral; Immunomodulating Agents
PubMed: 37768405
DOI: 10.1007/s11926-023-01116-7 -
Cureus Aug 2023Juvenile idiopathic arthritis (JIA) is a common form of arthritis that occurs in children, typically with an onset before the age of 16 years. It can affect joints in...
Juvenile idiopathic arthritis (JIA) is a common form of arthritis that occurs in children, typically with an onset before the age of 16 years. It can affect joints in any part of the body. As per the International League of Rheumatology, JIA is classified into systemic arthritis, oligoarthritis, extended oligoarthritis, polyarthritis (rheumatoid factor positive), polyarthritis (rheumatoid factor negative), enthesitis-related arthritis (ERA), juvenile psoriatic arthritis (JPsA), and . JIA is treated with disease-modifying antirheumatic medications (DMARDs), which include both nonbiologic agents like methotrexate (MTX) and biologic agents like inhibitors of tumor necrosis factor-alpha, interleukin-1 (IL-1), IL-6, and T-cell co-stimulation modulators. As per recent studies, in December 2021, Secukinumab, an IL-17A inhibitor, is one of the most recent biologic agents approved for active ERA and JPsA. A few reports have suggested Secukinumab is related to new-onset inflammatory bowel diseases (IBDs). We present a case of a 20-year-old female who was being treated with Secukinumab for JIA, and six months into therapy, she developed symptoms suggestive of Crohn's disease (CD). The diagnosis was confirmed with colonoscopy, histopathology, and radiology results. Her symptoms completely resolved four weeks after discontinuing Secukinumab and oral steroid therapy. The efficacy and side effects of Secukinumab have been studied mainly on middle-aged populations who were being treated for psoriasis and ankylosing spondylitis (AS); however, there is limited literature on younger populations. With this case report, we would like to highlight the possible relationship between the development of IBD and Secukinumab therapy in the adolescent population and emphasize the importance of regular screening for IBD in this population.
PubMed: 37736437
DOI: 10.7759/cureus.43825