Depression And Anxiety In Patients With Juvenile Idiopathic Arthritis: Current Insights And Impact On Quality Of Life, A Systematic Review

Depression and anxiety are prevalent in children with rheumatologic diseases, including juvenile idiopathic arthritis (JIA). However, prevalence rates and the relationship with disease outcomes, including quality of life are conflicting in the early literature. To review the current literature, determine gaps in our knowledge, and identify areas in need of further investigation, we conducted a systematic review of studies examining depression and anxiety symptoms among children with JIA and the impact these symptoms may have on disease outcomes and quality of life. Six electronic databases were searched up until January 2019. Of 799 potential articles, 60 articles were included with the main focus on 28 articles from 2009 to 2019, to concentrate on the most current evidence. We found that JIA patients experience symptoms of depression and anxiety similar to other childhood chronic diseases and at higher rates than in healthy children. Patients who experience these symptoms have worse quality of life, with some evidence pointing to depression and anxiety symptoms having a greater impact on quality of life than other disease features, such as active joint count. Family members of JIA patients experience high rates of anxiety and depression symptoms which may impact their child’s mental health and pain symptoms related to JIA. Conflicting reports of associations between depression/anxiety symptoms and disease features/disease outcomes and a paucity of longitudinal studies investigating the impact of treatment on mental health symptoms indicate areas in need of further research to effectively identify patients at greatest risk of depression and anxiety and to better understand how to treat and prevent these symptoms in youth with JIA. Family mental health should also be considered in investigations concerning mental health and disease outcomes of children with JIA

Deep Sequencing of Mixed Total DNA without Barcodes Allows Efficient Assembly of Highly Plastic Ascidian Mitochondrial Genomes

Ascidians or sea squirts form a diverse group within chordates, which includes a few thousand members of marine sessile filter-feeding animals. Their mitochondrial genomes are characterized by particularly high evolutionary rates and rampant gene rearrangements. This extreme variability complicates standard polymerase chain reaction (PCR) based techniques for molecular characterization studies, and consequently only a few complete Ascidian mitochondrial genome sequences are available. Using the standard PCR and Sanger sequencing approach, we produced the mitochondrial genome of Ascidiella aspersa only after a great effort. In contrast, we produced five additional mitogenomes (Botrylloides aff. leachii, Halocynthia spinosa, Polycarpa mytiligera, Pyura gangelion, and Rhodosoma turcicum) with a novel strategy, consisting in sequencing the pooled total DNA samples of these five species using one Illumina HiSeq 2000 flow cell lane. Each mitogenome was efficiently assembled in a single contig using de novo transcriptome assembly, as de novo genome assembly generally performed poorly for this task. Each of the new six mitogenomes presents a different and novel gene order, showing that no syntenic block has been conserved at the ordinal level (in Stolidobranchia and in Phlebobranchia). Phylogenetic analyses support the paraphyly of both Ascidiacea and Phlebobranchia, with Thaliacea nested inside Phlebobranchia, although the deepest nodes of the Phlebobranchia–Thaliacea clade are not well resolved. The strategy described here thus provides a cost-effective approach to obtain complete mitogenomes characterized by a highly plastic gene order and a fast nucleotide/amino acid substitution rate

Delays to Care in Pediatric Lupus Patients: Data From the Childhood Arthritis and Rheumatology Research Alliance Legacy Registry.

OBJECTIVE: Prompt treatment for lupus is important to prevent morbidity. A potential barrier to early treatment of pediatric lupus is delayed presentation to a pediatric rheumatologist. To better understand factors contributing to delayed presentation among pediatric lupus patients, we examined differences in demographic and clinical characteristics of lupus patients within the Childhood Arthritis and Rheumatology Research Alliance (CARRA) Legacy Registry with regard to time between symptom onset and presentation to a pediatric rheumatologist. METHODS: We analyzed data from 598 CARRA Legacy Registry participants for differences between those who presented early (withinonset), between 1-3 months (typical presentation), with moderate delays (3-12 months), and with severe delays (≥1 year). Factors associated with early presentation, moderate delay, and severe delay were determined by multinomial logistic regression. RESULTS: Forty-four percent of patients presented early, while 23% had moderate delays and 9% had severe delays. Family history of lupus, absence of discoid rash, and location in a state with a higher density of pediatric rheumatologists were associated with earlier presentation. Younger age, low household income ( CONCLUSION: Delays to care ≥1 year exist in a notable minority of pediatric lupus patients from the CARRA Legacy Registry. In this large and diverse sample of patients, access to care and family resources played an important role in predicting time to presentation to a pediatric rheumatologist

Urinary TWEAK as a biomarker of lupus nephritis: a multicenter cohort study

Introduction: TNF-like weak inducer of apoptosis (TWEAK) has been implicated as a mediator of chronic inflammatory processes via prolonged activation of the NF-κB pathway in several tissues, including the kidney. Evidence for the importance of TWEAK in the pathogenesis of lupus nephritis (LN) has been recently introduced. Thus, TWEAK levels may serve as an indication of LN presence and activity. Methods: Multicenter cohorts of systemic lupus erythematosus (SLE) patients and controls were recruited for cross-sectional and longitudinal analysis of urinary TWEAK (uTWEAK) and/or serum TWEAK (sTWEAK) levels as potential biomarkers of LN. The performance of TWEAK as a biomarker for nephritis was compared with routinely used laboratory tests in lupus patients, including anti-double stranded DNA antibodies and levels of C3 and C4. Results: uTWEAK levels were significantly higher in LN patients than in non-LN SLE patients and other disease control groups (P = 0.039). Furthermore, uTWEAK was better at distinguishing between LN and non-LN SLE patients than anti-DNA antibodies and complement levels, while high uTWEAK levels predicted LN in SLE patients with an odds ratio of 7.36 (95% confidence interval = 2.25 to 24.07; P = 0.001). uTWEAK levels peaked during LN flares, and were significantly higher during the flare than at 4 and 6 months prior to or following the flare event. A linear mixed-effects model showed a significant association between uTWEAK levels in SLE patients and their disease activity over time (P = 0.008). sTWEAK levels, however, were not found to correlate with the presence of LN or the degree of nephritis activity. Conclusions: High uTWEAK levels are indicative of LN, as opposed to non-LN SLE and other healthy and disease control populations, and reflect renal disease activity in longitudinal follow-up. Thus, our study further supports a role for TWEAK in the pathogenesis of LN, and provides strong evidence for uTWEAK as a candidate clinical biomarker for LN

The case for open science: rare diseases.

The premise of Open Science is that research and medical management will progress faster if data and knowledge are openly shared. The value of Open Science is nowhere more important and appreciated than in the rare disease (RD) community. Research into RDs has been limited by insufficient patient data and resources, a paucity of trained disease experts, and lack of therapeutics, leading to long delays in diagnosis and treatment. These issues can be ameliorated by following the principles and practices of sharing that are intrinsic to Open Science. Here, we describe how the RD community has adopted the core pillars of Open Science, adding new initiatives to promote care and research for RD patients and, ultimately, for all of medicine. We also present recommendations that can advance Open Science more globally

Prioritized Agenda for Mental Health Research in Pediatric Rheumatology from the Childhood Arthritis and Rheumatology Research Alliance Mental Health Workgroup

Objective Mental health problems are prevalent in youth with rheumatologic disease. Gaps in knowledge exist regarding their effect, as well as strategies for detection and effective treatment. To address these gaps, the Childhood Arthritis and Rheumatology Research Alliance (CARRA) Mental Health Workgroup developed and prioritized an agenda of research topics. Methods We systematically reviewed the literature and identified 5 major research domains in further need of study: (A) mental health burden and relationship to pediatric rheumatologic disease, (B) effect of mental health disorders on outcomes, (C) mental health awareness and education, (D) mental health screening, and (E) mental health treatment. Research topics within these areas were developed by workgroup leaders and refined by the workgroup. Members were surveyed to prioritize the topics by importance, feasibility of study, and actionability. Results Fifty-nine members (57%) completed the survey. Among the proposed research topics, 31/33 were rated as highly important and 4/33 were rated highly for importance, feasibility, and actionability. Topics rated most important related to (A) mental health burden and relationship to rheumatologic disease, and (B) the effect of mental health on outcomes. Topics rated most feasible and actionable were related to (D) mental health screening. Conclusion Addressing gaps in knowledge regarding mental health in youth with rheumatologic disease is essential for improving care. We have identified high priority research topics regarding mental health of pediatric rheumatology patients in need of further investigation that are feasible to study and believed to lead to actionable results in patient care

Mental health care for youth with rheumatologic diseases – bridging the gap

Abstract Youth with rheumatologic diseases have a high prevalence of comorbid mental health disorders. Individuals with comorbid mental health disorders are at increased risk for adverse outcomes related to mental health as well as their underlying rheumatologic disease. Early identification and treatment of mental health disorders has been shown to improve outcomes, but current systems of care fall short in providing adequate mental health services to those in need. Pediatric rheumatologists are uniquely positioned to provide mental health screening and intervention for youth with rheumatologic diseases due to the frequency of patient encounters and ongoing therapeutic relationship with patients and families. However, additional training is likely required for pediatric rheumatologists to provide effective mental health care, and focusing efforts on providing trainees with mental health education is key to building competency. Potential opportunities for improved mental health education include development of clinical guidelines regarding mental health screening and management within pediatric rheumatology settings and incorporation of mental health didactics, workshops, and interdisciplinary clinic experiences into pediatric rheumatology fellowship curricula. Additional steps include mental health education for patients and families and focus on system change, targeting integration of medical and mental health care. Research is needed to better define the scope of the problem, determine effective strategies for equipping pediatric rheumatologists with skills in mental health intervention, and develop and implement sustainable systems for delivery of optimal mental health care to youth with rheumatologic diseases

An Ecological Approach to Understanding and Addressing Health Inequities of SLE

Systemic Lupus Erythematosus (SLE) is a complex chronic autoimmune disease disproportionally afflicting women and Black, Indigenous, and other People of Color (BIPoC). In North America, these groups of people are also exposed to unique and harmful systemic social stressors (i.e., racism, sexism, economic inequality) that produce, maintain, and worsen negative health outcomes. Negative health outcomes attributable to disenfranchising systemic issues are known as health inequities. Though SLE disproportionately afflicts disenfranchised groups like BIPoC people and women, relatively little literature examines how systems issues confer health inequities among these groups. Therefore, we developed a community-engaged partnership with two cSLE diagnosed women of color to identify relevant system’s issues impacting SLE health outcomes. Then, using Cochrane guidelines, we conducted a rapid review of original research into SLE health outcomes into to these issues. We adapted an ecological model to illustrate the connection between systems issues and SLE outcomes. Finally, we provide recommendations for ways to research and clinically mitigate SLE health inequities