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The transition of patients with a chronic rheumatic disease from pediatric to adult care has been characterized by poor medical and patient-centered outcomes due to the lack of comprehensive transition programs and the paucity of evidence to guide practitioners. We describe a multidisciplinary transition program, data assessing patients’ preparedness for transition and perception of care providers, and the association between these outcomes.

Background: Chronic inflammatory diseases, such as juvenile idiopathic arthritis (JIA) and Crohn's disease (CD), are characterized by pro-inflammatory status, which can alter bone metabolism. This predisposes children with JIA and CD to low bone mineral content and higher risk of bone fracture. Exercise is an effective approach to strengthen bone and increase bone accrual in healthy and children with inflammatory conditions. This may be linked to mechanical loading or delayed anti-inflammatory effects of exercise, which can trigger bone turnover. The aim of this study was to utilize an in vitro model to examine the effects of exercise and inflammation on osteoblast proliferation. Methods: Serum samples from 30 youth (JIA n=8,13.36 ± 2.37 years; CD n=9,14.08 ± 2.44 years; and Controls n=13,14.10 ± 2.52 years) that participated in a previous exercise study were analyzed using in vitro experiments. The exercise protocol consisted of two 30-minute bouts of cycling at 50% of their peak mechanical power. Blood samples were collected at rest, immediately post-exercise, and at 1 hour of recovery. Inflammatory status was assessed by measuring cytokines IL-6 and tumor necrosis factor-α (TNF-α) in resting serum using high-sensitivity ELISA kits. Serum samples were also used to incubate MC3T3E1 osteoblasts in vitro for 48-hours. Osteoblast proliferation was measured using an MTS assay. Effects of exercise and inflammation were analyzed using one-way and two-way ANOVA while relationships between osteoblast proliferation and inflammatory status and aerobic fitness were analyzed using Pearson correlation. Results: There was no significant difference in osteoblast proliferation between JIA, CD, and healthy controls at rest (F=0.967, p=0.392). Exercise did not cause any significant effects on osteoblast proliferation between groups (F=0.0377, p=0.578,). Furthermore, osteoblast proliferation was not related to inflammatory status at rest (r = -0.149-0.243, p>0.05) or aerobic fitness (r=-0.164, p=0.412).Discussion: Exercise and chronic disease did not present any significant effects on in vitro osteoblast proliferation. This may be attributed to a delayed osteoblast response, which may be preceded by upstream signaling molecules of osteoblast proliferation, as well as effective disease management in JIA and CD patients, which may have attenuated inflammatory status. Further investigation is required. [ABSTRACT FROM AUTHOR]

Responds to E.J. Duryea's critical comments on a report entitled `Effects of a school-based alcohol education program with a media prevention component,' which appeared in `Psychological Reports.' Methodological concerns that were raised by Duryea; Concerns about the brevity of the intervention; More.

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., (© The Author(s) 2023. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Objective: Adolescents with chronic rheumatic disease must increasingly take on more responsibility for disease management from parents as they transition from pediatric to adult care. Yet, there are limited resources to inform and support parents about transition. Here, we evaluate the impact of a Transition Toolkit, geared towards parents and adolescents, on transition readiness, and explore the potential impact of parent-adolescent communication., Methods: A prospective cohort study of youths aged 14-18 years old and their parents was performed. Participant demographics, disease characteristics, transition readiness scores (Transition-Q, max 100), and parent-adolescent communication scores (PACS, max 100) were collected at enrollment (when the Transition Toolkit was shared with adolescents and their parents. Generalized estimating equation (GEE) analyses determined the influence of the Toolkit on transition readiness and explored the role of parent-adolescent communication quality. Subgroup analyses were conducted by sex., Results: A total of 21 patients were included; 19 completed one post-intervention Transition-Q and 16 completed two. Transition-Q scores increased over time and the rate of increase doubled after the Toolkit was shared (β = 7.8, p < 0.05, and β = 15.5, p < 0.05, respectively)., Conclusion: Transition readiness improved at each follow-up, the greatest increase was seen after the Toolkit was shared. Parent-adolescent communication quality did not appear to impact changes in transition readiness.

Background: The transition from pediatric to adult care is a critical time when adolescent patients and their families face many challenges. This period can be associated with an increase in disease-related morbidity and mortality. The aim of our study is to identify gaps in transition-related care to help guide areas for improvement., Methods: Patients (14-19 years) with juvenile idiopathic arthritis or systemic lupus erythematosus and one of their parents were recruited from the McMaster Rheumatology Transition Clinic. Both were asked to complete the Mind the Gap questionnaire, a validated tool to assess experience and satisfaction with transition care in a clinic setting. The questionnaire, addressing 3 important domains of care: management of the environment, provider characteristics, and process issues, was completed twice-once based on their current clinical experience and again based on their ideal clinical encounter. Positive scores suggest current care is less than ideal; negative scores suggest current care exceeds the ideal experience., Results: Most patients (n = 65, 68% female) had a diagnosis of juvenile idiopathic arthritis (87%). Patients identified mean gap scores between 0.2 and 0.3 for each domain of Mind the Gap, with female patients having higher gap scores compared with male patients. Parents (n = 51) identified gap scores between 0.0 and 0.3. Patients identified process issues as having the largest gap, whereas parents identified management of the environment as having the largest gap., Conclusions: We identified several gaps in transition clinic care relative to what patients and parents identify as ideal. These can be used to improve the rheumatology transition care that is currently being provided., Competing Interests: The authors declare no conflict of interest., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Objective: The COVID-19 pandemic has disrupted healthcare delivery and clinical research worldwide, with data from areas most affected demonstrating an impact on rheumatology care. This study aimed to characterize the impact of the pandemic on the initial presentation of JIA and JIA-related research in Canada., Methods: Data collected from the Canadian Alliance of Pediatric Rheumatology Investigators JIA Registry from the year pre-pandemic (11 March 2019 to 10 March 2020) was compared with data collected during the first year of the pandemic (11 March 2020 to 10 March 2021). Outcomes included time from symptom onset to first assessment, disease severity at presentation and registry recruitment. Proportions and medians were used to describe categorical and continuous variables, respectively., Results: The median time from symptom onset to first assessment was 138 (IQR 64-365) days pre-pandemic vs 146 (IQR 83-359) days during the pandemic. The JIA category frequencies remained overall stable (44% oligoarticular JIA pre-pandemic, 46.8% pandemic), except for systemic JIA (12 cases pre-pandemic, 1 pandemic). Clinical features, disease activity (cJADAS10), disability (CHAQ) and quality of life (JAQQ) scores were similar between the two cohorts. Pre-pandemic, 225 patients were enrolled, compared with 111 in the pandemic year, with the greatest decrease from March to June 2020., Conclusions: We did not observe the anticipated delay in time to presentation or increased severity at presentation, suggesting that, within Canada, care adapted well to provide support to new patient consults without negative impacts. The COVID-19 pandemic was associated with an initial 50% decrease in registry enrolment but has since improved., (© The Author(s) 2021. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Abstract: There is a paucity of information about the epidemiology, pathophysiology, and treatment of patients with a dual diagnosis of inflammatory bowel disease (IBD) and chronic recurrent multifocal osteomyelitis (CRMO). A retrospective chart review was performed of patients at McMaster Children's Hospital with a diagnosis of either IBD or CRMO, to identify those with the dual diagnosis over a 10-year period. A dual diagnosis was identified in seven patients. Most patients (6/7) had a diagnosis of IBD first and were subsequently diagnosed with CRMO. At the time of CRMO diagnosis, IBD treatment regimens included one or more of, sulfasalazine (1/6), infliximab (3/6), adalimumab (1/6), or no treatment (1/6). Although the etiology of the link remains unknown, there does not seem to be an association to a specific IBD subtype, age, or treatment. Our patient population demonstrated a response to biologic agents, specifically tumor necrosis factor-α inhibitors, as treatment for both conditions., Competing Interests: The authors report no conflicts of interest., (Copyright © 2021 by European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition.)

Objective: To create an international consensus treatment recommendation for pediatric NMDA receptor antibody encephalitis (NMDARE)., Methods: After selection of a panel of 27 experts with representation from all continents, a 2-step Delphi method was adopted to develop consensus on relevant treatment regimens and statements, along with key definitions in pediatric NMDARE (disease severity, failure to improve, and relapse). Finally, an online face-to-face meeting was held to reach consensus (defined as ≥75% agreement)., Results: Corticosteroids are recommended in all children with NMDARE (pulsed IV preferred), with additional IV immunoglobulin or plasma exchange in severe patients. Prolonged first-line immunotherapy can be offered for up to 3-12 months (oral corticosteroids or monthly IV corticosteroids/immunoglobulin), dependent on disease severity. Second-line treatments are recommended for cases refractory to first-line therapies (rituximab preferred over cyclophosphamide) and should be considered about 2 weeks after first-line initiation. Further immunotherapies for refractory disease 1-3 months after second-line initiation include another second-line treatment (such as cyclophosphamide) and escalation to tocilizumab. Maintenance immune suppression beyond 6 months (such as rituximab redosing or mycophenolate mofetil) is generally not required, except for patients with a more severe course or prolonged impairments and hospitalization. For patients with relapsing disease, second-line and prolonged maintenance therapy should be considered. The treatment of NMDARE following herpes simplex encephalitis should be similar to idiopathic NMDARE. Broad guidance is provided for the total treatment duration (first line, second line, and maintenance), which is dictated by the severity and clinical course (i.e., median 3, 9 and 18 months in the best, average, and worst responders, respectively). Recommendations on the timing of oncologic searches are provided., Conclusion: These international consensus recommendations for the management of pediatric NMDARE aim to standardize the treatment and provide practical guidance for clinicians, rather than absolute rules. A similar recommendation could be applicable to adult patients., (Copyright © 2021 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.)

Objective: The transition from pediatric to adult rheumatology care represents a particularly vulnerable time for patients with juvenile idiopathic arthritis (JIA) and childhood-onset systemic lupus erythematosus (cSLE). Improving self-management skills is important in optimizing health care transition. The study's objectives were to 1) examine variability in transition readiness of adolescents and young adults within and between different ages, sexes, and disease types; 2) determine the association between age and transition readiness; and 3) identify specific challenges to transition readiness for adolescents., Methods: Over 1 year, patients 14 to 20 years of age with JIA or cSLE were recruited from pediatric transition and young adult clinics at a single academic institution. Participants completed the 14-item Transition-Q at a single time point. Total scores range from 0 to 100; higher scores indicate greater health care self-management skills as a proxy for transition readiness. Descriptive statistics summarized patient characteristics and Transition-Q scores for the population. Regression analyses determined the association between age, sex, and disease type and Transition-Q score., Results: Among 70 participants, 61 had JIA and 9 cSLE (mean disease duration 4.6 years). The mean (SD) total Transition-Q score was 59.8 (14.9). Age was significantly associated with Transition-Q score (standardized β = 0.372l P = 0.002). The most commonly reported challenges were seeing the physician alone (without parents), making one's own appointments, picking up prescriptions, and independent transportation for appointments., Conclusion: Transition readiness appears to increase with patient age. There is significant variability in Transition-Q scores between patients of the same age, suggesting that an individualized approach to improving self-management skills is necessary., (© 2021 The Authors. ACR Open Rheumatology published by Wiley Periodicals LLC on behalf of American College of Rheumatology.)

Background: Juvenile idiopathic arthritis (JIA) is a serious and potentially debilitating pediatric illness. Improved disease self-management may help to improve health outcomes., Objective: This study aimed to evaluate the effectiveness of the Teens Taking Charge Web-based self-management intervention in reducing symptoms and improving health-related quality of life (HRQL) in adolescents with JIA compared with a Web-based education control condition., Methods: Adolescents with JIA aged 12 to 18 years were recruited from 11 Canadian pediatric rheumatology centers. Caregivers were invited to participate along with their child. In addition to standard medical care, participants were randomized to receive either (1) the Teens Taking Charge self-management intervention or (2) a Web-based education control condition for a period of 12 weeks. Adolescents in the intervention group completed website modules addressing cognitive behavioral coping skills, stress management, and other self-management topics, while also receiving monthly telephone calls from a trained health coach. Adolescents in the education control group were instructed to view a series of preselected public JIA educational websites and received monthly calls from a coach who asked about their own best efforts at managing JIA. Caregivers in the intervention group completed website modules related to promoting independence and disease self-management in their child. Caregivers in the education control group were instructed to view a series of preselected public JIA educational websites. Outcome assessment occurred at baseline, 12 weeks (posttreatment), and at 6 and 12 months postrandomization. The primary outcomes were pain intensity, pain interference, and HRQL. Secondary outcomes were emotional symptoms, adherence, coping, knowledge, and self-efficacy., Results: In total, 333 adolescents and 306 caregivers were enrolled. Significant overall reductions in pain intensity (P=.02) and pain interference (P=.007) were observed for intervention group participants compared with those in the education control group, after adjusting for baseline levels. There was a significant overall improvement in HRQL related to problems with pain (P=.02) and problems with daily activities (P=.01). There was also a significant difference in the intervention group over time (P=.008) for HRQL related to treatment problems, with the intervention group participants demonstrating improved HRQL by 12 months compared with education control group participants. Both groups showed nonsignificant improvements compared with baseline in other primary outcomes. There were no significant differences between the groups in any secondary outcomes or caregiver-reported outcomes., Conclusions: The results of this randomized trial suggest that the Teens Taking Charge Web-based intervention is effective at reducing both pain intensity and pain interference, as well as improving HRQL in adolescents with JIA, compared with education control. These effects are sustained for up to 12 months following program completion. The Teens Taking Charge program is now publicly available at no cost., Trial Registration: ClinicalTrials.gov NCT01572896; https://clinicaltrials.gov/ct2/show/NCT01572896., (©Jennifer N Stinson, Chitra Lalloo, Amos S Hundert, Sarah Campillo, Tania Cellucci, Paul Dancey, Ciaran Duffy, Janet Ellsworth, Brian M Feldman, Adam M Huber, Nicole Johnson, Geert't Jong, Kiem Oen, Alan M Rosenberg, Natalie J Shiff, Lynn Spiegel, Shirley M L Tse, Lori Tucker, Joseph Charles Victor. Originally published in the Journal of Medical Internet Research (http://www.jmir.org), 29.07.2020.)

Objective: To identify barriers and facilitators to the uptake of information from research by parents of children with juvenile idiopathic arthritis (JIA)., Methods: Parents of children with JIA participated in focus group and telephone interviews at four Canadian pediatric rheumatology centers. The semistructured interviews focused on perceptions about JIA research, how new information about JIA was obtained and used, and what information was of most interest. Transcripts were analyzed using a general inductive approach., Results: Twenty-eight parents participated in the study. Parents were very interested in research that addresses the outcomes of JIA and side effects of medications. Parents communicated an expectation that information from research be communicated to them by their child's pediatric rheumatologist as part of clinical care. Parents felt that it would be helpful to have information available to them in a variety of formats including written, video, and online. The timing of information delivery is an important factor, with parents being most interested and engaged in learning about new information about JIA at diagnosis and disease flares. We found that parents were overall unaware of new findings from JIA research and therefore may not be optimally utilizing this potentially helpful information in the care of their children., Conclusion: This study has led to an understanding of Canadian parents' perceptions about research and existing gaps in the translation of research knowledge. This information will facilitate the development, implementation, and evaluation of future knowledge translation interventions aimed at improving the uptake of research information in the care of children with JIA., (© 2020 The Authors. ACR Open Rheumatology published by Wiley Periodicals, Inc. on behalf of American College of Rheumatology.)

Objective: Autoimmune encephalitis (AE) is an important and treatable cause of acute encephalitis. Diagnosis of AE in a developing child is challenging because of overlap in clinical presentations with other diseases and complexity of normal behavior changes. Existing diagnostic criteria for adult AE require modification to be applied to children, who differ from adults in their clinical presentations, paraclinical findings, autoantibody profiles, treatment response, and long-term outcomes., Methods: A subcommittee of the Autoimmune Encephalitis International Working Group collaborated through conference calls and email correspondence to consider the pediatric-specific approach to AE. The subcommittee reviewed the literature of relevant AE studies and sought additional input from other expert clinicians and researchers., Results: Existing consensus criteria for adult AE were refined for use in children. Provisional pediatric AE classification criteria and an algorithm to facilitate early diagnosis are proposed. There is also discussion about how to distinguish pediatric AE from conditions within the differential diagnosis., Conclusions: Diagnosing AE is based on the combination of a clinical history consistent with pediatric AE and supportive diagnostic testing, which includes but is not dependent on antibody testing. The proposed criteria and algorithm require validation in prospective pediatric cohorts., (Copyright © 2020 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.)

Objective: This study examined differences in substance use, depression, and academic functioning among ADHD and non-ADHD college students. Participants: Included 1,748 students (ages 18-25; women 68.4%; Caucasian 71.3%) with and without history of ADHD. Methods: We assessed the relationship of ADHD to substance use variables, controlling for depressive symptoms and examined relationships with GPA. Results: ADHD students were more likely to have engaged in frequent alcohol use, binge drinking, regular marijuana use and to have used other drugs in the last year. They reported higher depression symptoms than non-ADHD students, although substance abuse risk remained high even when controlling for depressive symptoms. ADHD students had lower overall GPA than those without ADHD. However, this difference was no longer significant when controlling for depression and marijuana use. Conclusions: College campuses should consider programing aimed at identifying ADHD students at risk for developing substance abuse problems and emotional difficulties.

Objective: To determine barriers and facilitators to the uptake of findings from the Research in Arthritis in Canadian Children emphasizing Outcomes (ReACCh-Out) study into clinical care by pediatric rheumatologists (PR) and allied health professionals (AHP) caring for children with juvenile idiopathic arthritis (JIA) in Canada., Methods: PR and AHP participated in this qualitative study through telephone interviews. Interview guides were developed using the Theoretical Domains Framework and focused on the use of information from the ReACCh-Out study in the practice of counseling patients and families. A directed content analysis approach was used for coding., Results: Nineteen interviews (8 PR and 11 AHP) were completed. All PR had knowledge of the ReACCh-Out study. Three major themes were identified: (1) both groups are motivated to use information from research in clinical care; (2) volume and emotional effect of information on families are barriers; and (3) specific timepoints in care trigger providing this information. AHP had less knowledge of the ReACCh-Out study, did not feel it was their primary role to provide this information, and have a desire for more opportunity to participate in academic forums related to research., Conclusion: We have described a comprehensive overview of the barriers and facilitators perceived by healthcare providers in the translation of knowledge from JIA research into use in clinical practice. These findings provide a foundation for the development of knowledge translation strategies in the care of children with JIA and other rheumatic diseases.

Objective: To develop standardized treatment regimens for chronic nonbacterial osteomyelitis (CNO), also known as chronic recurrent multifocal osteomyelitis (CRMO), to enable comparative effectiveness treatment studies., Methods: Virtual and face-to-face discussions and meetings were held within the CNO/CRMO subgroup of the Childhood Arthritis and Rheumatology Research Alliance (CARRA). A literature search was conducted, and CARRA membership was surveyed to evaluate available treatment data and identify current treatment practices. Nominal group technique was used to achieve consensus on treatment plans for CNO refractory to nonsteroidal antiinflammatory drug (NSAID) monotherapy and/or with active spinal lesions., Results: Three consensus treatment plans (CTPs) were developed for the first 12 months of therapy for CNO patients refractory to NSAID monotherapy and/or with active spinal lesions. The 3 CTPs are methotrexate or sulfasalazine, tumor necrosis factor inhibitors with optional methotrexate, and bisphosphonates. Short courses of glucocorticoids and continuation of NSAIDs are permitted for all regimens. Consensus was achieved on these CTPs among CARRA members. Consensus was also reached on subject eligibility criteria, initial evaluations that should be conducted prior to the initiation of CTPs, and data items to collect to assess treatment response., Conclusion: Three consensus treatment plans were developed for pediatric patients with CNO refractory to NSAIDs and/or with active spinal lesions. Use of these CTPs will provide additional information on efficacy and will generate meaningful data for comparative effectiveness research in CNO., (© 2017, American College of Rheumatology.)

Rare rheumatic diseases present unique challenges to knowledge translation (KT) researchers. There is often an urgent need to transfer knowledge from research findings into clinical practice to facilitate earlier diagnosis and better outcomes. However, existing KT frameworks have not addressed the specific considerations surrounding rare diseases for which gold standard evidence is not available. Several widely adopted models provide guidance for processes and problems associated with KT. However, they do not address issues surrounding creation or synthesis of knowledge for rare diseases. Additional problems relate to lack of awareness or experience in intended knowledge users, low motivation, and potential barriers to changing practice or policy. Strategies to address the challenges of KT for rare rheumatic diseases include considering different levels of evidence available, linking knowledge creation and transfer directly, incorporating patient and physician advocacy efforts to generate awareness of conditions, and selecting strategies to address barriers to practice or policy change.

Encephalitis is a severe inflammatory disorder of the brain with many possible causes and a complex differential diagnosis. Advances in autoimmune encephalitis research in the past 10 years have led to the identification of new syndromes and biomarkers that have transformed the diagnostic approach to these disorders. However, existing criteria for autoimmune encephalitis are too reliant on antibody testing and response to immunotherapy, which might delay the diagnosis. We reviewed the literature and gathered the experience of a team of experts with the aims of developing a practical, syndrome-based diagnostic approach to autoimmune encephalitis and providing guidelines to navigate through the differential diagnosis. Because autoantibody test results and response to therapy are not available at disease onset, we based the initial diagnostic approach on neurological assessment and conventional tests that are accessible to most clinicians. Through logical differential diagnosis, levels of evidence for autoimmune encephalitis (possible, probable, or definite) are achieved, which can lead to prompt immunotherapy., Competing Interests: Declaration of interests FG receives royalties from licensing fees to Euroimmun for the use of IgLON5 as a diagnostic test. MJT has received research funding for consultancy work for MedImmune, and a travel grant for Sun Pharma. CGB has given scientific advice to Eisai and UCB; undertaken industry-funded travel with support from Eisai, UCB, Desitin, and Grifols; obtained honoraria for speaking engagements from Eisai, UCB, Desitin, Diamed, Fresenius Medical Care; and received research support from Astellas Pharma, Octapharma, Diamed, and Fresenius Medical Care. CGB is an employee of Krankenhaus Mara, Bielefeld, Germany, which runs a laboratory for the detection of autoantibodies including those described in this paper; external senders are charged for antibody diagnostics. RCD has received research funding from the Star Scientific Foundation and Pfizer Neuroscience and speaker’s honoraria from Biogen Idec and Bristol-Myers Squibb. JMG has received compensation for medical legal consulting and for consulting on a scientific advisory board for Medimmune and Roche; he has received research funding through the University of California, San Francisco, USA, from Quest Diagnostic for work on a dementia care pathway. MG receives grants from Quest Diagnostics and has received personal fees for consultancy work from MedaCorp, Gerson-Lehman Group, Best Doctors, Advance Medical, Inc, and Optio LLC. JH receives royalties from licensing fees to Athena Diagnostics, Euroimmun, and ravo Diagnostika for a patent for the use of CV2/CRMP5 as diagnostic tests. SRI receives royalties from licensing fees to Euroimmun for patents for the use of LGI1, CASPR2, and contactin-2 as autoantibody tests. EL has received speaker’s honoraria and consultancy fees from Grifols, and consultancy fees from Medimmune. FL has received speaker’s honoraria from Grifols, Teva, and Biogen Idec and is employed by University Medical Center Schleswig-Holstein, Kiel, Germany, which offers commercial antibody testing without any personal reimbursements. MR reports that his employers, the University Hospital and Medical University of Innsbruck, Austria, receive payments for antibody assays (NMDA receptor, AQP4, and other autoantibodies) and for AQP4 antibody validation experiments organised by Euroimmun. MRR receives royalties from licensing fees to Euroimmun for a patent for the use of NMDA receptor as an autoantibody test, and from licensing fees to Athena Diagnostics for a patent for the use of Ma2. AS has received compensation for consulting services and speaker honoraria from Bayer-Schering, Merck-Serono, Biogen Idec, Sanofi-Aventis, Teva, and Novartis. AVe reports personal fees from Medimmune. AVi receives royalties from licensing fees to Euroimmun for the use of LGI1 and CASPR2 as diagnostic tests. PW receives royalties for the use of LGI1 and CASPR2 as autoantibody diagnostic tests; is a named inventor on a patent for the use of GABAA receptor as an autoantibody test; and has received speaker honoraria from Biogen Idec and Euroimmun. JD receives royalties from licensing fees to Athena Diagnostics for a patent for the use of Ma2 as an autoantibody test; licensing fees to Euroimmun for patents for the use of NMDA receptor and GABAB receptor as autoantibody tests; licensing fees for the use of DPPX, GABAA receptor, and IgLON5 antibodies as diagnostic tests; and has received a research grant from Euroimmun. RB, SB, TC, IC, CAG, RH, TI, HP, AR-G, KR, and K-PW declare no competing interests. None of the funding sources had any influence in the preparation of this Position Paper., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Background: Youth with juvenile idiopathic arthritis (JIA) may be at risk of poor cardiovascular health. Circulating endothelial progenitor cells (EPCs) and circulating endothelial cells (CECs) are markers of cardiovascular repair and damage, respectively, and respond to exercise. The objectives of this study were to compare resting levels of EPCs and CECs in JIA and controls, and to assess the effects of distinct types of exercise on EPCs and CECs in JIA and controls., Methods: Seven youth with JIA and six controls completed 3 visits. First, aerobic fitness was assessed. Participants then performed either moderate intensity, continuous exercise (MICE) or high intensity, intermittent exercise (HIIE) on separate days. Blood samples were collected at the beginning (REST), mid-point (MID) and end of exercise (POST) for determination of EPCs (CD31(+)CD34(bright)CD45(dim)CD133(+)) and CECs (CD31(bright)CD34(+)CD45(-)CD133(-)) by flow cytometry. Between group differences in EPCs and CECs were examined using two-way ANOVA, followed by Tukey's HSD post hoc, where appropriate. Statistical significance set at p ≤ 0.05., Results: Both EPCs and CECs were similar between groups at REST (p = 0.18-0.94). During MICE, EPCs remained unchanged in JIA (p = 0.95) but increased significantly at POST in controls (REST: 0.91 ± 0.55 × 10(6) cells/L vs. POST: 1.53 ± 0.36 × 10(6) cells/L, p = 0.04). Compared with controls, lower levels of EPCs were observed in JIA at MID (0.48 ± 0.50 × 10(6) cells/L vs. 1.10 ± 0.39 × 10(6) cells/L, p = 0.01) and POST (0.38 ± 0.34 × 10(6) cells/L vs. 1.53 ± 0.36 × 10(6) cells/L, p < 0.001) during MICE. No changes were detected in CECs with MICE in JIA and controls (p = 0.69). Neither EPCs nor CECs were modified with HIIE (p = 0.28-0.69)., Conclusion: Youth with JIA demonstrated a blunted EPC response to MICE when compared with controls. Future work should examine factors that may increase or normalize EPC mobilization in JIA.

Objective: To report the clinical, radiological, and immunological association of demyelinating disorders with anti–Nmethyl- D-aspartate receptor (NMDAR) encephalitis., Methods: Clinical and radiological analysis was done of a cohort of 691 patients with anti-NMDAR encephalitis. Determination of antibodies to NMDAR, aquaporin-4 (AQP4), and myelin oligodendrocyte glycoprotein (MOG) was performed using brain immunohistochemistry and cell-based assays., Results: Twenty-three of 691 patients with anti-NMDAR encephalitis had prominent magnetic resonance imaging (MRI) and/or clinical features of demyelination. Group 1 included 12 patients in whom anti-NMDAR encephalitis was preceded or followed by independent episodes of neuromyelitis optica (NMO) spectrum disorder (5 cases, 4 anti-AQP4 positive) or brainstem or multifocal demyelinating syndromes (7 cases, all anti-MOG positive). Group 2 included 11 patients in whom anti-NMDAR encephalitis occurred simultaneously with MRI and symptoms compatible with demyelination (5 AQ4 positive, 2 MOG positive). Group 3 (136 controls) included 50 randomly selected patients with typical anti-NMDAR encephalitis, 56 with NMO, and 30 with multiple sclerosis; NMDAR antibodies were detected only in the 50 anti-NMDAR patients, MOG antibodies in 3 of 50 anti-NMDAR and 1 of 56 NMO patients, and AQP4 antibodies in 48 of 56 NMO and 1 of 50 anti-NMDAR patients (p<0.0001 for all comparisons with Groups 1 and 2). Most patients improved with immunotherapy, but compared with anti-NMDAR encephalitis the demyelinating episodes required more intensive therapy and resulted in more residual deficits. Only 1 of 23 NMDAR patients with signs of demyelination had ovarian teratoma compared with 18 of 50 anti-NMDAR controls (p50.011)., Interpretation: Patients with anti-NMDAR encephalitis may develop concurrent or separate episodes of demyelinating disorders, and conversely patients with NMO or demyelinating disorders with atypical symptoms (eg, dyskinesias, psychosis) may have anti-NMDAR encephalitis.

Objective: To identify distinct clusters of children with inflammatory brain diseases based on clinical, laboratory, and imaging features at presentation, to assess which features contribute strongly to the development of clusters, and to compare additional features between the identified clusters., Methods: A single-center cohort study was performed with children who had been diagnosed as having an inflammatory brain disease between June 1, 1989 and December 31, 2010. Demographic, clinical, laboratory, neuroimaging, and histologic data at diagnosis were collected. K-means cluster analysis was performed to identify clusters of patients based on their presenting features. Associations between the clusters and patient variables, such as diagnoses, were determined., Results: A total of 147 children (50% female; median age 8.8 years) were identified: 105 with primary central nervous system (CNS) vasculitis, 11 with secondary CNS vasculitis, 8 with neuronal antibody syndromes, 6 with postinfectious syndromes, and 17 with other inflammatory brain diseases. Three distinct clusters were identified. Paresis and speech deficits were the most common presenting features in cluster 1. Children in cluster 2 were likely to present with behavior changes, cognitive dysfunction, and seizures, while those in cluster 3 experienced ataxia, vision abnormalities, and seizures. Lesions seen on T2/fluid-attenuated inversion recovery sequences of magnetic resonance imaging were common in all clusters, but unilateral ischemic lesions were more prominent in cluster 1. The clusters were associated with specific diagnoses and diagnostic test results., Conclusion: Children with inflammatory brain diseases presented with distinct phenotypical patterns that are associated with specific diagnoses. This information may inform the development of a diagnostic classification of childhood inflammatory brain diseases and suggest that specific pathways of diagnostic evaluation are warranted., (Copyright © 2014 by the American College of Rheumatology.)

Background: Increasing evidence suggests that seizures and status epilepticus can be immune-mediated. We aimed to describe the clinical features of a new epileptic disorder, and to establish the target antigen and the effects of patients' antibodies on neuronal cultures., Methods: In this observational study, we selected serum and CSF samples for antigen characterisation from 140 patients with encephalitis, seizures or status epilepticus, and antibodies to unknown neuropil antigens. The samples were obtained from worldwide referrals of patients with disorders suspected to be autoimmune between April 28, 2006, and April 25, 2013. We used samples from 75 healthy individuals and 416 patients with a range of neurological diseases as controls. We assessed the samples using immunoprecipitation, mass spectrometry, cell-based assay, and analysis of antibody effects in cultured rat hippocampal neurons with confocal microscopy., Findings: Neuronal cell-membrane immunoprecipitation with serum of two index patients revealed GABAA receptor sequences. Cell-based assay with HEK293 expressing α1/β3 subunits of the GABAA receptor showed high titre serum antibodies (>1:160) and CSF antibodies in six patients. All six patients (age 3-63 years, median 22 years; five male patients) developed refractory status epilepticus or epilepsia partialis continua along with extensive cortical-subcortical MRI abnormalities; four patients needed pharmacologically induced coma. 12 of 416 control patients with other diseases, but none of the healthy controls, had low-titre GABAA receptor antibodies detectable in only serum samples, five of them also had GAD-65 antibodies. These 12 patients (age 2-74 years, median 26.5 years; seven male patients) developed a broader spectrum of symptoms probably indicative of coexisting autoimmune disorders: six had encephalitis with seizures (one with status epilepticus needing pharmacologically induced coma; one with epilepsia partialis continua), four had stiff-person syndrome (one with seizures and limbic involvement), and two had opsoclonus-myoclonus. Overall, 12 of 15 patients for whom treatment and outcome were assessable had full (three patients) or partial (nine patients) response to immunotherapy or symptomatic treatment, and three died. Patients' antibodies caused a selective reduction of GABAA receptor clusters at synapses, but not along dendrites, without altering NMDA receptors and gephyrin (a protein that anchors the GABAA receptor)., Interpretation: High titres of serum and CSF GABAA receptor antibodies are associated with a severe form of encephalitis with seizures, refractory status epilepticus, or both. The antibodies cause a selective reduction of synaptic GABAA receptors. The disorder often occurs with GABAergic and other coexisting autoimmune disorders and is potentially treatable., Funding: The National Institutes of Health, the McKnight Neuroscience of Brain Disorders, the Fondo de Investigaciones Sanitarias, Fundació la Marató de TV3, the Netherlands Organisation for Scientific Research (Veni-incentive), the Dutch Epilepsy Foundation., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Objective: To compare clinical, laboratory, and imaging characteristics of childhood primary angiitis of the central nervous system (PACNS) subtypes at diagnosis and during followup; to characterize disease activity trajectories in childhood PACNS subtypes; and to identify early risk factors for higher disease activity., Methods: We performed a single-center cohort study of consecutive children diagnosed as having childhood PACNS. Demographic, clinical, laboratory, and imaging data were collected at diagnosis and during standardized clinic visits. Outcome measures included disease activity measured by physician's global assessment. Descriptive statistics were used to assess characteristics of the study cohort, and longitudinal data were analyzed using linear mixed-effects regression., Results: The study cohort consisted of 45 patients with childhood PACNS; 26 had angiography-negative childhood PACNS and 19 had angiography-positive childhood PACNS. There were 24 females, the median age at diagnosis was 9.8 years, and the median followup period was 1.8 years. Patients with angiography-negative childhood PACNS were more likely to be female and to present with seizures, cognitive dysfunction, vision abnormalities, high levels of inflammatory markers, and bilateral findings on magnetic resonance imaging (MRI). Motor deficits and ischemic MRI lesions were more common in angiography-positive disease. Disease activity decreased significantly after treatment in all patients. Distinct trajectories of disease activity over time were identified for both childhood PACNS subtypes. Patients with angiography-negative childhood PACNS had persistently higher disease activity. Seizures at presentation also predicted higher disease activity over time., Conclusion: Distinct subtypes of childhood PACNS have unique disease activity trajectories. Patients with angiography-negative disease and seizures at presentation experience higher disease activity. Early recognition of this high-risk cohort may enable the treating physician to initiate targeted therapies and prevent long-term brain injury., (Copyright © 2012 by the American College of Rheumatology.)

Incarcerated women have high rates of substance abuse problems and trauma. A variety of variables may influence whether these women seek help or are referred for substance abuse problems. This study reports an exploratory project on service utilization among incarcerated substance-dependent women (N = 40) in southeastern Idaho. Using self-report and interview tools, most participants reported some substance abuse treatment history, although extent and types of treatment varied. Most of the women also reported some type of childhood abuse. Age, income, and consequences of alcohol and other drug use related positively to substance abuse treatment. However, severity of childhood sexual abuse and current trauma symptoms were negatively correlated with substance abuse treatment episodes. These women may use substances to cope with childhood trauma or may not perceive the substance abuse system as responsive to their co-occurring trauma symptoms., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Purpose of Review: To review the current literature of childhood central nervous system vasculitis, and to discuss a tailored approach to diagnosis and treatment based on recent evidence., Recent Findings: Primary angiitis of the central nervous system in children (cPACNS) is an increasingly recognized inflammatory brain disease with potentially devastating neurological consequences. The diagnostic approach should be tailored to the clinical presentation of the child with suspected cPACNS and should address the expanding spectrum of inflammatory and noninflammatory brain diseases with overlapping clinical features. New evidence has confirmed that elective brain biopsies in children have a higher diagnostic yield than in adults and improve our ability to diagnose angiography-negative cPACNS. Finally, observational studies have shown that early diagnosis and aggressive treatment lead to improved neurological outcomes and lower mortality rates in patients with cPACNS., Summary: This review summarizes the recent data on diagnosis, classification, treatment, and outcomes in cPACNS. Our improved understanding of cPACNS facilitates a tailored diagnostic approach that results in earlier diagnosis and initiation of therapy for this potentially reversible condition.

Objectives: To describe Salmonella infections in children presenting to the Children's Hospital (London Health Sciences Centre, London, Ontario), to assess risk factors for infection and to examine whether younger children, particularly infants younger than 12 weeks of age, experience higher morbidity than older children., Methods: A 10-year retrospective review of children with Salmonella infections at the Children's Hospital was conducted. Patient demographics, risk factors for infection, clinical characteristics, bacteriology and outcome were collected from the hospital charts and laboratory records. Data were separated into groups based on age and recent use of antibiotics to analyze differences in outcomes., Results: Sixty-six children with Salmonella infections presented to the Children's Hospital over a 10-year period. Common risk factors for Salmonella infection included having sick contacts, living in a rural area, recent travel, contact with pets (especially reptiles) and exposure to local water. Younger age was associated with an increased likelihood of admission to hospital, treatment with antibiotics and a longer course of antibiotic therapy. This was true when comparing older infants with those younger than 12 weeks of age. Patients recently treated with antibiotics and those with significant underlying medical conditions were more likely to be admitted., Conclusions: A wider knowledge of the epidemiological risk factors for Salmonella infection may improve diagnosis. Higher admission rates were expected in children younger than 12 weeks of age, those recently treated with antibiotics and those who had a significant underlying medical condition. A prospective, multicentre study is needed to further address questions regarding increased illness severity and appropriate management of Salmonella infections in children younger than 12 weeks of age.

There is increasing interest regarding the role of maladaptive cognition in Borderline Personality Disorder (BPD). The current study examined the relationship between early maladaptive schema (EMS) domains and BPD symptoms as well as whether schema domains account for the relationship between childhood maltreatment and BPD severity. Incarcerated women (N=105) were assessed for BPD symptoms via semi-structured diagnostic interview. Disconnection/Rejection and Impaired Limits were associated with BPD pathology although these domains shared variance with depression and antisocial personality disorder pathology, respectively. In addition, the relationship between childhood abuse and BPD severity was non-significant after controlling for schema domains. Related findings and the implications for cognitive treatment of BPD are discussed.

The number of university students requesting services based on the Americans with Disabilities Act for learning disabilities and ADHD-related difficulties has increased, although there are limited reports in the literature describing these evaluations. The current study describes a sample of 140 individuals (59% women) who presented for psycho-educational evaluation at the university psychology clinic. The students were individually administered self-report, cognitive, academic, and attention measures as indicated, and diagnosed according to the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV). Difficulties with mathematics, attention, and reading concerns were the most frequent presenting complaints. 46 students met criteria for one or more learning disorders and 20 students met criteria for a diagnosis of ADHD. Test scores are summarized and findings compared with the literature.

This study examined the association of borderline personality disorder (BPD) and antisocial personality disorder (ASPD) with substance dependence among incarcerated females (N=105) as well as the influence of the co-occurrence of BPD and ASPD on psychosocial functioning in substance-dependent participants. The severity of BPD and ASPD both were associated with drug dependence, but BPD was not associated with alcohol dependence. After controlling for ASPD severity, BPD severity was no longer associated with drug dependence. The ASPD features of criminal activity and recklessness were most uniquely associated with drug and alcohol dependence (respectively). None of the BPD features was uniquely associated with alcohol or drug dependence after controlling for ASPD. A co-occurring BPD diagnosis was associated with mood disturbance and experiential avoidance among substance-dependent participants. An ASPD diagnosis was associated with an earlier age at first arrest, along with greater childhood abuse and severity of alcohol dependence. These findings have important implications for further understanding and developing ways to help substance-dependent incarcerated females.