345 results on '"Laxer RM"'
Search Results
2. A missense mutation in the MLKL brace region promotes lethal neonatal inflammation and hematopoietic dysfunction
- Author
-
Hildebrand, JM, Kauppi, M, Majewski, IJ, Liu, Z, Cox, AJ, Miyake, S, Petrie, EJ, Silk, MA, Li, Z, Tanzer, MC, Brumatti, G, Young, SN, Hall, C, Garnish, SE, Corbin, J, Stutz, MD, Di Rago, L, Gangatirkar, P, Josefsson, EC, Rigbye, K, Anderton, H, Rickard, JA, Tripaydonis, A, Sheridan, J, Scerri, TS, Jackson, VE, Czabotar, PE, Zhang, J-G, Varghese, L, Allison, CC, Pellegrini, M, Tannahill, GM, Hatchell, EC, Willson, TA, Stockwell, D, de Graaf, CA, Collinge, J, Hilton, A, Silke, N, Spall, SK, Chau, D, Athanasopoulos, V, Metcalf, D, Laxer, RM, Bassuk, AG, Darbro, BW, Singh, MAF, Vlahovich, N, Hughes, D, Kozlovskaia, M, Ascher, DB, Warnatz, K, Venhoff, N, Thiel, J, Biben, C, Blum, S, Reveille, J, Hildebrand, MS, Vinuesa, CG, McCombe, P, Brown, MA, Kile, BT, McLean, C, Bahlo, M, Masters, SL, Nakano, H, Ferguson, PJ, Murphy, JM, Alexander, WS, Silke, J, Hildebrand, JM, Kauppi, M, Majewski, IJ, Liu, Z, Cox, AJ, Miyake, S, Petrie, EJ, Silk, MA, Li, Z, Tanzer, MC, Brumatti, G, Young, SN, Hall, C, Garnish, SE, Corbin, J, Stutz, MD, Di Rago, L, Gangatirkar, P, Josefsson, EC, Rigbye, K, Anderton, H, Rickard, JA, Tripaydonis, A, Sheridan, J, Scerri, TS, Jackson, VE, Czabotar, PE, Zhang, J-G, Varghese, L, Allison, CC, Pellegrini, M, Tannahill, GM, Hatchell, EC, Willson, TA, Stockwell, D, de Graaf, CA, Collinge, J, Hilton, A, Silke, N, Spall, SK, Chau, D, Athanasopoulos, V, Metcalf, D, Laxer, RM, Bassuk, AG, Darbro, BW, Singh, MAF, Vlahovich, N, Hughes, D, Kozlovskaia, M, Ascher, DB, Warnatz, K, Venhoff, N, Thiel, J, Biben, C, Blum, S, Reveille, J, Hildebrand, MS, Vinuesa, CG, McCombe, P, Brown, MA, Kile, BT, McLean, C, Bahlo, M, Masters, SL, Nakano, H, Ferguson, PJ, Murphy, JM, Alexander, WS, and Silke, J
- Abstract
MLKL is the essential effector of necroptosis, a form of programmed lytic cell death. We have isolated a mouse strain with a single missense mutation, MlklD139V, that alters the two-helix 'brace' that connects the killer four-helix bundle and regulatory pseudokinase domains. This confers constitutive, RIPK3 independent killing activity to MLKL. Homozygous mutant mice develop lethal postnatal inflammation of the salivary glands and mediastinum. The normal embryonic development of MlklD139V homozygotes until birth, and the absence of any overt phenotype in heterozygotes provides important in vivo precedent for the capacity of cells to clear activated MLKL. These observations offer an important insight into the potential disease-modulating roles of three common human MLKL polymorphisms that encode amino acid substitutions within or adjacent to the brace region. Compound heterozygosity of these variants is found at up to 12-fold the expected frequency in patients that suffer from a pediatric autoinflammatory disease, chronic recurrent multifocal osteomyelitis (CRMO).
- Published
- 2020
3. In silico validation of the autoinflammatory disease damage index
- Author
-
ter Haar, Nm, van Delft, Alj, Annink, Kv, van Stel, H, Al-Mayouf, Sm, Amaryan, G, Anton, J, Barron, K, Benseler, S, Brogan, Pa, Cantarini, L, Cattalini, M, Cochino, Av, De Benedetti, F, Dedeoglu, F, de Jesus, Aa, Demirkaya, E, Dolezalova, P, Durrant, Kl, Fabio, G, Gallizzi, R, Goldbach-Mansky, R, Hachulla, E, Hentgen, V, Herlin, T, Hofer, M, Hoffman, Hm, Insalaco, A, Jansson, Af, Kallinich, T, Koné-Paut, I, Kozlova, A, Kuemmerle-Deschner, Jb, Lachmann, Hj, Laxer, Rm, Martini, A, Nielsen, S, Nikishina, I, Ombrello, Ak, Özen, S, Papadopoulou-Alataki, E, Quartier, P, Rigante, Donato, Russo, R, Simon, A, Trachana, M, Uziel, Y, Ravelli, A, Schulert, G, Gattorno, M, Frenkel, J, Rigante D (ORCID:0000-0001-7032-7779), ter Haar, Nm, van Delft, Alj, Annink, Kv, van Stel, H, Al-Mayouf, Sm, Amaryan, G, Anton, J, Barron, K, Benseler, S, Brogan, Pa, Cantarini, L, Cattalini, M, Cochino, Av, De Benedetti, F, Dedeoglu, F, de Jesus, Aa, Demirkaya, E, Dolezalova, P, Durrant, Kl, Fabio, G, Gallizzi, R, Goldbach-Mansky, R, Hachulla, E, Hentgen, V, Herlin, T, Hofer, M, Hoffman, Hm, Insalaco, A, Jansson, Af, Kallinich, T, Koné-Paut, I, Kozlova, A, Kuemmerle-Deschner, Jb, Lachmann, Hj, Laxer, Rm, Martini, A, Nielsen, S, Nikishina, I, Ombrello, Ak, Özen, S, Papadopoulou-Alataki, E, Quartier, P, Rigante, Donato, Russo, R, Simon, A, Trachana, M, Uziel, Y, Ravelli, A, Schulert, G, Gattorno, M, Frenkel, J, and Rigante D (ORCID:0000-0001-7032-7779)
- Abstract
INTRODUCTION: Autoinflammatory diseases can cause irreversible tissue damage due to systemic inflammation. Recently, the Autoinflammatory Disease Damage Index (ADDI) was developed. The ADDI is the first instrument to quantify damage in familial Mediterranean fever, cryopyrin-associated periodic syndromes, mevalonate kinase deficiency and tumour necrosis factor receptor-associated periodic syndrome. The aim of this study was to validate this tool for its intended use in a clinical/research setting. METHODS: The ADDI was scored on paper clinical cases by at least three physicians per case, independently of each other. Face and content validity were assessed by requesting comments on the ADDI. Reliability was tested by calculating the intraclass correlation coefficient (ICC) using an 'observer-nested-within-subject' design. Construct validity was determined by correlating the ADDI score to the Physician Global Assessment (PGA) of damage and disease activity. Redundancy of individual items was determined with Cronbach's alpha. RESULTS: The ADDI was validated on a total of 110 paper clinical cases by 37 experts in autoinflammatory diseases. This yielded an ICC of 0.84 (95% CI 0.78 to 0.89). The ADDI score correlated strongly with PGA-damage (r=0.92, 95% CI 0.88 to 0.95) and was not strongly influenced by disease activity (r=0.395, 95% CI 0.21 to 0.55). After comments from disease experts, some item definitions were refined. The interitem correlation in all different categories was lower than 0.7, indicating that there was no redundancy between individual damage items. CONCLUSION: The ADDI is a reliable and valid instrument to quantify damage in individual patients and can be used to compare disease outcomes in clinical studies.
- Published
- 2018
4. The pediatric rheumatology European Society American College of Rheumatology European league against rheumatism provisional classification criteria for juvenile systemic sclerosis
- Author
-
Zulian, Francesco, Woo, P, Athreya, Bh, Laxer, Rm, Medsger, Ta, Lehman, Tja, Cerinic, Mm, Martini, G, Ravelli, A, Russo, R, Cuttica, R, DE OLIVEIRA SKF, Denton, Cp, Cozzi, Franco, Foeldvari, I, and Ruperto, N.
- Published
- 2007
5. Sleep, fatigue and quality of life in juvenile idiopathic arthritis (JIA) and Juvenile Dermatomyositis (JDM)
- Author
-
Avie, Y Butbul, primary, Stremler, R, additional, Stinson, J, additional, Schneider, R, additional, Laxer, RM, additional, Spiegel, L, additional, Cameron, B, additional, Silverman, ED, additional, and Feldman, BM, additional
- Published
- 2008
- Full Text
- View/download PDF
6. Infliximab Therapie der refraktären systemischen Polyarteritis nodosa
- Author
-
Benseler, SM, primary, Parker, S, additional, Whitney Mahoney, K, additional, and Laxer, RM, additional
- Published
- 2003
- Full Text
- View/download PDF
7. The Current Status of the ‘Morbidity and Mortality Conference’ in University Affiliated Pediatric Departments in Canada
- Author
-
Friedman, JN, primary, Pinard, MS, additional, and Laxer, RM, additional
- Published
- 2003
- Full Text
- View/download PDF
8. New advances in juvenile spondyloarthritis.
- Author
-
Tse SM, Laxer RM, Tse, Shirley M L, and Laxer, Ronald M
- Abstract
Juvenile spondyloarthritis (SpA) is a distinct disease to adult SpA, and usually manifests as peripheral arthritis and enthesitis. Importantly, many patients with juvenile SpA continue to be at risk of developing ankylosing spondylitis during their disease course. In this Review, the classification and diagnostic criteria, clinical manifestations and treatment guidelines for juvenile SpA will be discussed. Advances in the diagnosis of and management strategies for juvenile SpA will lead to earlier recognition, appropriate treatment and improved rates of inactive disease, which should lead to improved patient outcomes and quality of life. [ABSTRACT FROM AUTHOR]
- Published
- 2012
- Full Text
- View/download PDF
9. En coup de sabre scleroderma and Parry-Romberg syndrome in adolescents: surgical options and patient-related outcomes [corrected] [published erratum appears in J RHEUMATOL 2010 Nov;37(11):2444].
- Author
-
Palmero MLH, Uziel Y, Laxer RM, Forrest CR, and Pope E
- Published
- 2010
- Full Text
- View/download PDF
10. Neurologic manifestations of localized scleroderma: a case report and literature review.
- Author
-
Kister I, Inglese M, Laxer RM, Herbert J, Kister, Ilya, Inglese, Matilde, Laxer, Ronald M, and Herbert, Joseph
- Published
- 2008
- Full Text
- View/download PDF
11. Early-onset osteoarthritis due to otospondylomegaepiphyseal dysplasia in a family with a novel splicing mutation of the COL11A2 gene.
- Author
-
Avcin T, Makitie O, Susic M, Miller S, Thorne C, Tenenbaum J, Laxer RM, Cole WG, Avcin, Tadej, Makitie, Outi, Susic, Miki, Miller, Stephen, Thorne, Carter, Tenenbaum, Jerry, Laxer, Ronald M, and Cole, William G
- Published
- 2008
12. The effects of vigorous exercise training on physical function in children with arthritis: a randomized, controlled, single-blinded trial.
- Author
-
Singh-Grewal D, Schneiderman-Walker J, Wright V, Bar-Or O, Beyene J, Selvadurai H, Cameron B, Laxer RM, Schneider R, Silverman ED, Spiegel L, Tse S, Leblanc C, Wong J, Stephens S, and Feldman BM
- Published
- 2007
13. Pamidronate treatment of chronic noninfectious inflammatory lesions of the mandible in children.
- Author
-
Compeyrot-Lacassagne S, Rosenberg AM, Babyn P, Laxer RM, Compeyrot-Lacassagne, Sandrine, Rosenberg, Alan M, Babyn, Paul, and Laxer, Ronald M
- Published
- 2007
14. Clinical features and outcome of pediatric Wegener's granulomatosis.
- Author
-
Akikusa JD, Schneider R, Harvey EA, Hebert D, Thorner PS, Laxer RM, and Silverman ED
- Published
- 2007
15. Epidemiology of juvenile idiopathic arthritis in a multiethnic cohort: ethnicity as a risk factor.
- Author
-
Saurenmann RK, Rose JB, Tyrrell P, Feldman BM, Laxer RM, Schneider R, and Silverman ED
- Abstract
OBJECTIVE: To study the influence of ethnicity on the risk of developing juvenile idiopathic arthritis (JIA) in a multiethnic community of patients with unrestricted access to health care. METHODS: A questionnaire on ethnicity was distributed to all patients with JIA being followed up at the Hospital for Sick Children in Toronto, Ontario, Canada. Of 1,082 patients, 859 (79.4%) responded to the questionnaire. To calculate the relative risk (RR) of developing JIA in this study cohort, the results were compared with data from the age-matched general population of the Toronto metropolitan area (TMA) as provided in the 2001 census from Statistics Canada. RESULTS: European descent was reported by 69.7% of the patients with JIA compared with a frequency of 54.7% in the TMA general population, whereas a statistically significantly lower than expected percentage of the patients with JIA reported having black, Asian, or Indian subcontinent origin. Children of European origin had a higher RR for developing any of the JIA subtypes except polyarticular rheumatoid factor (RF)-positive JIA, and were particularly more likely to develop the extended oligoarticular and psoriatic subtypes. A higher frequency of enthesitis-related JIA was observed among patients of Asian origin, while those of black origin or native North American origin were more likely to develop polyarticular RF-positive JIA. CONCLUSION: In this multiethnic cohort, European descent was associated with a significantly increased risk of developing JIA, and the distribution of JIA subtypes differed significantly across ethnic groups. [ABSTRACT FROM AUTHOR]
- Published
- 2007
- Full Text
- View/download PDF
16. The Pediatric Rheumatology European Society/American College of Rheumatology/European League against Rheumatism provisional classification criteria for juvenile systemic sclerosis.
- Author
-
Zulian F, Woo P, Athreya BH, Laxer RM, Medsger TA Jr., Lehman TJA, Cerinic MM, Martini G, Ravelli A, Russo R, Cuttica R, de Oliveira SKF, Denton CP, Cozzi F, Foeldvari I, Ruperto N, Pediatric Rheumatology European Society, American College of Rheumatology, and European League Against Rheumatism Ad Hoc on Classification Criteria for Juvenile Systemic Sclerosis
- Published
- 2007
17. Prevalence, risk factors, and outcome of uveitis in juvenile idiopathic arthritis: a long-term followup study.
- Author
-
Saurenmann RK, Levin AV, Feldman BM, Rose JB, Laxer RM, Schneider R, and Silverman ED
- Abstract
OBJECTIVE: To assess the prevalence, risk factors, and long-term outcome of uveitis in patients with juvenile idiopathic arthritis (JIA). METHODS: An inception cohort of all 1,081 patients diagnosed as having JIA at a single tertiary care center was established. A questionnaire and followup telephone calls were used to confirm the diagnosis of uveitis. Ophthalmologists' records of patients with uveitis were collected. Kaplan-Meier and Cox regression analyses were used to assess risk factors for developing uveitis and for complications of uveitis. RESULTS: After a mean followup time of 6.9 years, 142 of 1,081 patients (13.1%) had developed uveitis. Risk factors were young age at diagnosis, female sex, antinuclear antibody positivity, and the subtype of JIA. The relative contribution of these risk factors was different for the different subtypes of JIA. Until the end of the study, uveitis complications had developed in 53 of 142 patients with uveitis (37.3%; 4.9% of the total cohort). Only 16 of 175 involved eyes (9.1%) in 14 of 108 patients (13%; 1.3% of the total cohort) for whom ophthalmology reports were available had best corrected visual acuity less than 20/40 (mean followup time for uveitis of 6.3 years). Abnormal vision was associated with synechiae or cataract. CONCLUSION: Risk factors for developing uveitis were different among subtypes of JIA. The long-term outcome of JIA-associated uveitis in our cohort was excellent despite the high rate of complications. [ABSTRACT FROM AUTHOR]
- Published
- 2007
- Full Text
- View/download PDF
18. Risk of new-onset uveitis in patients with juvenile idiopathic arthritis treated with anti-TNFalpha agents.
- Author
-
Saurenmann RK, Levin AV, Feldman BM, Laxer RM, Schneider R, and Silverman ED
- Published
- 2006
- Full Text
- View/download PDF
19. Localized scleroderma.
- Author
-
Laxer RM and Zulian F
- Published
- 2006
- Full Text
- View/download PDF
20. Approach to acute limb pain in childhood.
- Author
-
Tse SML, Laxer RM, Tse, Shirley M L, and Laxer, Ronald M
- Published
- 2006
- Full Text
- View/download PDF
21. Angiography-negative primary central nervous system vasculitis in children: a newly recognized inflammatory central nervous system disease.
- Author
-
Benseler SM, deVeber G, Hawkins C, Schneider R, Tyrrell PN, Aviv RI, Armstrong D, Laxer RM, and Silverman ED
- Abstract
Inflammatory central nervous system (CNS) diseases in childhood comprise a wide spectrum of heterogeneous conditions. We studied 4 children with primary CNS vasculitis in whom results of magnetic resonance imaging studies were abnormal but results of conventional angiography were normal. We determined that angiography-negative, biopsy-confirmed primary small-vessel CNS vasculitis is a previously unrecognized distinct disease entity in children. The diagnosis must be considered in a child with a progressive, acquired diffuse or focal neurologic deficit, even if the results of conventional angiography are normal. A lesional brain biopsy is required to confirm the diagnosis. Use of immunosuppressive therapy plus aspirin leads to an excellent neurologic outcome. [ABSTRACT FROM AUTHOR]
- Published
- 2005
- Full Text
- View/download PDF
22. Anti-tumor necrosis factor alpha blockade in the treatment of juvenile spondylarthropathy.
- Author
-
Tse SML, Burgos-Vargas R, and Laxer RM
- Abstract
OBJECTIVE: Persistent inflammation refractory to standard antirheumatic therapy in children with juvenile spondylarthropathy (SpA) leads to morbidity and reduced quality of life. Tumor necrosis factor alpha (TNFalpha) plays an important role in the pathogenesis of synovitis and enthesitis. This study was undertaken to examine the impact of anti-TNFalpha agents on juvenile SpA that is refractory to nonsteroidal antiinflammatory drugs (NSAIDs), disease-modifying antirheumatic drugs, and corticosteroids. METHODS: Ten juvenile SpA patients with a mean +/- SEM age of 15.0 +/- 0.7 years and disease duration of 4.4 +/- 0.8 years, all of whom were HLA-B27 positive, were followed up for 1 year after initiation of either infliximab (n = 8) or etanercept (n = 2). Outcomes examined were within-subject differences in the tender entheseal count (TEC) and active joint count (AJC), markers of inflammation, functional assessments (Childhood Health Assessment Questionnaire [C-HAQ] score), and requirements for antirheumatic drugs. RESULTS: At baseline, all patients exhibited active arthritis and enthesitis that were resistant to NSAIDs (n = 10), methotrexate (n = 6), sulfasalazine (n = 8), corticosteroids (oral n = 6, intravenous pulse n = 3, and intraarticular n = 6), and bisphosphonates (n = 2). In 2 patients, sulfasalazine (n = 2), corticosteroids (n = 1), and bisphosphonates (n = 1) were stopped after initiation of the anti-TNFalpha agent. In all patients, the arthritis and enthesitis significantly improved as evidenced by remission of the TEC and AJC by 6 months that was sustained during the 1-year followup, markers of inflammation and C-HAQ scores normalized, and there was a reduction in requirements for antirheumatic drugs (reduced dosage or discontinuation of NSAIDs n = 10, methotrexate n = 5, sulfasalazine n = 6, corticosteroids n = 4, and bisphosphonates n = 1). CONCLUSION: Anti-TNFalpha therapy is a potential novel treatment for refractory juvenile SpA. Further prospective studies are required to examine the effectiveness and long-term outcomes of anti-TNFalpha therapy in this cohort. [ABSTRACT FROM AUTHOR]
- Published
- 2005
- Full Text
- View/download PDF
23. Increased anticardiolipin antibody IgG titers do not predict recurrent stroke or TIA in children.
- Author
-
Lanthier S, Kirkham FJ, Mitchell LG, Laxer RM, Atenafu E, Male C, Prengler M, Domi T, Chan AKC, Liesner R, deVeber G, Lanthier, S, Kirkham, F J, Mitchell, L G, Laxer, R M, Atenafu, E, Male, C, Prengler, M, Domi, T, and Chan, A K C
- Published
- 2004
- Full Text
- View/download PDF
24. The physical therapy practitioner (PTP) in pediatric rheumatology: high level of patient and parent satisfaction with services.
- Author
-
Campos AA, Graveline C, Ferguson JM, Lundon K, Feldman BM, Schneider R, and Laxer RM
- Published
- 2002
25. The physical therapy practitioner: an expanded role for physical therapy in pediatric rheumatology.
- Author
-
Campos AA, Graveline C, Ferguson JM, Lundon K, Schneider R, and Laxer RM
- Published
- 2001
26. Paediatric rheumatology workshop/series editor: P Woo. Long-term toxicity of immune suppression in juvenile rheumatic diseases.
- Author
-
Laxer, RM
- Published
- 1999
- Full Text
- View/download PDF
27. Lipoatrophy resulting from steroid injection into the temporomandibular joint.
- Author
-
Hugle B and Laxer RM
- Published
- 2009
- Full Text
- View/download PDF
28. Intestinal pseudoobstruction in Kawasaki disease.
- Author
-
Akikusa JD, Laxer RM, and Friedman JN
- Abstract
Intestinal pseudoobstruction is an uncommon but important manifestation of Kawasaki disease. Its occurrence at the onset or during the course of the disease may confuse the clinical picture and cause delay in diagnosis and treatment. This delay may be responsible for the high rate of coronary artery abnormalities that have been reported in patients with this complication. We suggest that Kawasaki disease be considered in the differential diagnosis of any child presenting with intestinal pseudoobstruction and fever without definable cause. [ABSTRACT FROM AUTHOR]
- Published
- 2004
- Full Text
- View/download PDF
29. Retrospective Review of Morphea in Paediatric Patients with Skin of Colour.
- Author
-
Mohsen ST, Park M, Pope E, Laxer RM, and Sibbald CJ
- Abstract
Competing Interests: Declaration of Conflicting InterestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.
- Published
- 2024
- Full Text
- View/download PDF
30. Interleukin-1-mediated hyperinflammation in XIAP deficiency is associated with defective autophagy.
- Author
-
Dissanayake D, Firouzabady A, Massumi M, de Paz Linares GA, Marshall C, Freeman SA, Laxer RM, and Yeung RSM
- Subjects
- Humans, Lymphohistiocytosis, Hemophagocytic genetics, Lymphohistiocytosis, Hemophagocytic pathology, Lymphohistiocytosis, Hemophagocytic metabolism, Inflammation metabolism, Inflammation pathology, Inflammation genetics, Inflammasomes metabolism, Male, Macrophages metabolism, Macrophages pathology, NLR Family, Pyrin Domain-Containing 3 Protein metabolism, NLR Family, Pyrin Domain-Containing 3 Protein genetics, NLR Family, Pyrin Domain-Containing 3 Protein deficiency, Female, X-Linked Inhibitor of Apoptosis Protein genetics, X-Linked Inhibitor of Apoptosis Protein deficiency, X-Linked Inhibitor of Apoptosis Protein metabolism, Autophagy, Interleukin-1beta metabolism
- Abstract
Abstract: Deficiency of X-linked inhibitor of apoptosis protein (XIAP) is a rare genetic condition that can present with recurrent episodes of hemophagocytic lymphohistiocytosis (HLH), though the exact mechanisms leading to this hyperinflammatory disorder are unclear. Understanding its biology is critical to developing targeted therapies for this potentially fatal disease. Here, we report on a novel multiexonic intragenic duplication leading to XIAP deficiency with recurrent HLH that demonstrated complete response to interleukin (IL)-1β blockade. We further demonstrate using both primary patient cells and genetically modified THP-1 monocyte cell lines that, contrary to what has previously been shown in mouse cells, XIAP-deficient human macrophages do not produce excess IL-1β when stimulated under standard conditions. Instead, nucleotide-binding oligomerization domain-like receptor family pyrin domain containing 3 (NLRP3) inflammasome-mediated hyperproduction of IL-1β is observed only when the XIAP-deficient cells are stimulated under autophagy-promoting conditions and this correlates with defective autophagic flux as measured by decreased accumulation of the early autophagy marker LC3-II. This work, therefore, highlights IL-1β blockade as a therapeutic option for patients with XIAP deficiency experiencing recurrent HLH and identifies a critical role for XIAP in promoting autophagy as a means of limiting IL-1β-mediated hyperinflammation during periods of cellular stress., (© 2024 American Society of Hematology. Published by Elsevier Inc. All rights are reserved, including those for text and data mining, AI training, and similar technologies.)
- Published
- 2024
- Full Text
- View/download PDF
31. A decade of progress in juvenile idiopathic arthritis treatments and outcomes in Canada: results from ReACCh-Out and the CAPRI registry.
- Author
-
Nguyen K, Barsalou J, Basodan D, Batthish M, Benseler SM, Berard RA, Blanchette N, Boire G, Bolaria R, Bruns A, Cabral DA, Cameron B, Campillo S, Cellucci T, Chan M, Chédeville G, Chetaille AL, Chhabra A, Couture J, Dancey P, De Bruycker JJ, Demirkaya E, Dhalla M, Duffy CM, Feldman BM, Feldman DE, Gerschman T, Haddad E, Heale L, Herrington J, Houghton K, Huber AM, Human A, Johnson N, Jurencak R, Lang B, Larché M, Laxer RM, LeBlanc CM, Lee JJY, Levy DM, Lim L, Lim LSH, Luca N, McGrath T, McMillan T, Miettunen PM, Morishita KA, Ng HY, Oen K, Park J, Petty RE, Proulx-Gauthier JP, Ramsey S, Roth J, Rosenberg AM, Rozenblyum E, Rumsey DG, Schmeling H, Schneider R, Scuccimarri R, Shiff NJ, Silverman E, Soon G, Spiegel L, Stringer E, Tam H, Tse SM, Tucker LB, Turvey S, Twilt M, Duffy KW, Yeung RSM, and Guzman J
- Subjects
- Humans, Canada epidemiology, Male, Female, Child, Treatment Outcome, Adolescent, Child, Preschool, Biological Products therapeutic use, Severity of Illness Index, Arthritis, Juvenile drug therapy, Registries, Antirheumatic Agents therapeutic use
- Abstract
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.)
- Published
- 2024
- Full Text
- View/download PDF
32. Autoinflammatory Diseases: A Review.
- Author
-
An J, Marwaha A, and Laxer RM
- Subjects
- Humans, Inflammation, Autoimmune Diseases genetics, Hereditary Autoinflammatory Diseases genetics, Hereditary Autoinflammatory Diseases immunology, Hereditary Autoinflammatory Diseases diagnosis
- Abstract
Autoinflammatory disease (AID) is a vast spectrum of disorders characterized by recurrent attacks of sterile inflammation. Since the first cloning of the familial Mediterranean fever gene in 1997, there has been a rapid rate of discovery of new AIDs. As of 2022, there have been 485 inborn errors of immunity documented by the International Union of Immunological Societies, for which many display aspects of autoinflammation. The pathophysiology of AIDs is complex. Although many are caused by rare mutations in genes that govern innate immunity, others are polygenic, where disease expression is thought to be triggered by environmental factors in genetically predisposed hosts. AIDs range in prevalence from common entities like gout to ultrarare monogenic diseases. Whereas AIDs were initially studied in pediatric populations, it is now apparent that they can present in adulthood and even in the elderly. AIDs can be clinically challenging given their rarity, as well as the heterogeneity in presentation and underlying etiology. Although the care of AIDs can span medical disciplines, the rheumatologist often plays a central role given the inflammatory nature of these illnesses. In this review, we explore the current understanding of the pathophysiology of these complex conditions and propose a classification system for AIDs. We place an emphasis on AIDs that present to the adult rheumatologist and discuss important AIDs that can mimic more classic rheumatic diseases such as systemic lupus erythematosus and inflammatory arthritis. Finally, we offer an approach to the clinical assessment, diagnosis, and management of AIDs., (Copyright © 2024 by the Journal of Rheumatology.)
- Published
- 2024
- Full Text
- View/download PDF
33. Using a collaborative learning health system approach to improve disease activity outcomes in children with juvenile idiopathic arthritis in the Pediatric Rheumatology Care and Outcomes Improvement Network.
- Author
-
Harris JG, Bingham CA, Vora SS, Yildirim-Toruner C, Batthish M, Bullock DR, Burnham JM, Fair DC, Ferraro K, Ganguli S, Gilbert M, Gottlieb BS, Halyabar O, Hazen MM, Laxer RM, Lee TC, Liu A, Lovell DJ, Mannion ML, Oberle EJ, Pan N, Shishov M, Weiss JE, and Morgan EM
- Abstract
Introduction: The Pediatric Rheumatology Care and Outcomes Improvement Network (PR-COIN) is a North American learning health network focused on improving outcomes of children with juvenile idiopathic arthritis (JIA). JIA is a chronic autoimmune disease that can lead to morbidity related to persistent joint and ocular inflammation. PR-COIN has a shared patient registry that tracks twenty quality measures including ten outcome measures of which six are related to disease activity. The network's global aim, set in 2021, was to increase the percent of patients with oligoarticular or polyarticular JIA that had an inactive or low disease activity state from 76% to 80% by the end of 2023., Methods: Twenty-three hospitals participate in PR-COIN, with over 7,200 active patients with JIA. The disease activity outcome measures include active joint count, physician global assessment of disease activity, and measures related to validated composite disease activity scoring systems including inactive or low disease activity by the 10-joint clinical Juvenile Arthritis Disease Activity Score (cJADAS10), inactive or low disease activity by cJADAS10 at 6 months post-diagnosis, mean cJADAS10 score, and the American College of Rheumatology (ACR) provisional criteria for clinical inactive disease. Data is collated to measure network performance, which is displayed on run and control charts. Network-wide interventions have included pre-visit planning, shared decision making, self-management support, population health management, and utilizing a Treat to Target approach to care., Results: Five outcome measures related to disease activity have demonstrated significant improvement over time. The percent of patients with inactive or low disease activity by cJADAS10 surpassed our goal with current network performance at 81%. Clinical inactive disease by ACR provisional criteria improved from 46% to 60%. The mean cJADAS10 score decreased from 4.3 to 2.6, and the mean active joint count declined from 1.5 to 0.7. Mean physician global assessment of disease activity significantly improved from 1 to 0.6., Conclusions: PR-COIN has shown significant improvement in disease activity metrics for patients with JIA. The network will continue to work on both site-specific and collaborative efforts to improve outcomes for children with JIA with attention to health equity, severity adjustment, and data quality., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2024 Harris, Bingham, Vora, Yildirim-Toruner, Batthish, Bullock, Burnham, Fair, Ferraro, Ganguli, Gilbert, Gottlieb, Halyabar, Hazen, Laxer, Lee, Liu, Lovell, Mannion, Oberle, Pan, Shishov, Weiss and Morgan.)
- Published
- 2024
- Full Text
- View/download PDF
34. Classification Criteria for Axial Disease in Youth with Juvenile Spondyloarthritis.
- Author
-
Weiss PF, Brandon TG, Aggarwal A, Burgos-Vargas R, Colbert RA, Horneff G, Laxer RM, Minden K, Ravelli A, Ruperto N, Smith JA, Stoll ML, Tse SM, Van den Bosch F, Maksymowych WP, Lambert RG, Biko DM, Chauvin NA, Francavilla ML, Jaremko JL, Herregods N, Kasapcopur O, Yildiz M, Srinivasalu H, Lovell DJ, Nigrovic PA, Foeldvari I, Klein-Gitelman MS, Ozen S, Naden R, Hendry AM, and Joos R
- Abstract
Objectives: To develop and validate classification criteria for axial disease in youth with juvenile spondyloarthritis (SpA; AxJSpA)., Methods: This international initiative consisted of four phases: 1) Item generation; 2) Item reduction; 3) Criteria development; and 4) Validation of the AxJSpA criteria by an independent team of experts in an internationally representative Validation cohort., Results: These criteria are intended to be used on youth with a physician diagnosis of juvenile SpA and for whom axial disease is suspected. Item generation consisted of a systematic literature review and a free-listing exercise using input from international physicians and collectively resulted in 108 items. After the item reduction exercise and expert panel input, 37 items remained for further consideration. The final AxJSpA criteria domains included: imaging: active inflammation, imaging: structural lesions, pain chronicity, pain pattern, pain location, stiffness, and genetics. The most heavily weighted domains were active inflammation and structural lesions on imaging. Imaging typical of sacroiliitis was deemed necessary, but not sufficient, to classify a youth with AxJSpA. The threshold for classification of AxJSpA was a score of ≥55 (out of 100). When tested in the validation data set, the final criteria had a specificity of 97.5% (95% CI: 91.4-99.7), sensitivity of 64.3% (95% CI: 54.9-73.1) and Area Under the Receiver Operating Characteristic (AUROC) curve of 0.81 (95% CI: 0.76-0.86)., Conclusions: The new AxJSpA classification criteria require an entry criterion, physician diagnosis of juvenile SpA, and include seven weighted domains. The AxJSpA classification criteria are validated and designed to identify participants for research studies., (This article is protected by copyright. All rights reserved.)
- Published
- 2024
- Full Text
- View/download PDF
35. Capturing the Range of Disease Involvement in Localized Scleroderma: The Localized Scleroderma Total Severity Scale.
- Author
-
Li SC, Rabinovich CE, Becker ML, Torok KS, Ferguson PJ, Dedeoglu F, Hong S, Sivaraman V, Laxer RM, Stewart K, Ibarra MF, Mason T 2nd, Higgins G, Pope E, Li X, Lozy T, and Fuhlbrigge RC
- Subjects
- Humans, Female, Male, Child, Reproducibility of Results, Adolescent, Feasibility Studies, Prospective Studies, Consensus, Observer Variation, Scleroderma, Localized diagnosis, Scleroderma, Localized physiopathology, Scleroderma, Localized complications, Severity of Illness Index, Scleroderma, Systemic
- Abstract
Objective: Juvenile localized scleroderma (jLS) is a chronic autoimmune disease commonly associated with poor outcomes, including contractures, hemiatrophy, uveitis, and seizures. Despite improvements in treatment, >25% of patients with jLS have functional impairment. To improve patient evaluation, our workgroup developed the Localized scleroderma Total Severity Scale (LoTSS), an overall disease severity measure., Methods: LoTSS was developed as a weighted measure by a consensus process involving literature review, surveys, case vignettes, and multicriteria decision analysis. Feasibility was assessed in larger Childhood Arthritis and Rheumatology Research Alliance groups. Construct validity with physician assessment and inter-rater reliability was assessed using case vignettes. Additional evaluation was performed in a prospective patient cohort initiating treatment., Results: LoTSS severity items were organized into modules that reflect jLS disease patterns, with modules for skin, extracutaneous, and craniofacial manifestations. Construct validity of LoTSS was supported by a strong positive correlation with the Physician Global Assessment (PGA) of severity and damage and weak positive correlation with PGA-Activity, as expected. LoTSS was responsive, with a small effect size identified. Moderate-to-excellent inter-rater reliability was demonstrated. LoTSS was able to discriminate between patient subsets, with higher scores identified in those with greater disease burden and functional limitation., Conclusion: We developed a new LS measure for assessing cutaneous and extracutaneous severity and have shown it to be reliable, valid, and responsive. LoTSS is the first measure that assesses and scores all the major extracutaneous manifestations in LS. Our findings suggest LoTSS could aid assessment and management of patients and facilitate outcome evaluation in treatment studies., (© 2023 American College of Rheumatology.)
- Published
- 2024
- Full Text
- View/download PDF
36. Systematic Review of Health-Related Quality of Life Impact in Juvenile Localized Scleroderma.
- Author
-
Sanchez-Espino LF, Luca N, Pope E, Laxer RM, Knight AM, and Sibbald C
- Subjects
- Humans, Child, Adolescent, Male, Female, Child, Preschool, Self Concept, Scleroderma, Systemic, Quality of Life, Scleroderma, Localized psychology
- Abstract
Objective: The prevalence and types of psychosocial complications of juvenile localized scleroderma (JLS), also known as morphea, an inflammatory and sclerosing disease involving the skin, fascia, muscle, and bone, are poorly understood., Methods: We performed a systematic review of literature published between 2000 and 2020 in PubMed, EMBASE, the Cochrane Skin Group Specialized Register, the Cochrane Central Register of Controlled Trials, and the Cumulative Index to Nursing and Allied Health Literature using the search terms "scleroderma, localized," "Morphea," "anxiety," "depression," "resilience," "social stigma," "quality of life," "mood," or "stress" and limited the search to pediatric patients and English language. Patient demographics, characteristics of JLS, and comorbidities were extracted. The outcomes included measures of health-related quality of life (HRQoL), psychosocial functioning, evaluation of self-perception, and the treatment burden of the study population. The protocol was registered with PROSPERO (CRD42021257124). Thematic synthesis generated descriptive analysis., Results: Thirteen studies fulfilled the inclusion criteria: three retrospective cohort studies, two prospective cohort studies, and eight cross-sectional studies. A total of 690 pediatric patients with JLS were included (n = 484 with linear scleroderma). Six studies used the Children's Dermatology Life Quality Index, reporting little to no effect on HRQoL. One study used the Health-Related Quality of Life in Children and Adolescents Questionnaire and did not find differences between children with JLS or atopic dermatitis and healthy controls. One study used a self-perception questionnaire that showed normal self-worth of patients with JLS. Two studies used focus groups, both reporting elevated levels of stress, decreased self-worth, "feeling different," and bullying/teasing in patients with JLS. These emotions were associated with skin symptoms (pain, itch, and tightness), physical limitations, and treatment burden., Conclusion: Overall, quantitative studies did not report a statistically significant impairment in HRQoL in JLS. However, qualitative studies (focus groups) reported significant psychosocial impacts related to JLS. There is a need to develop a JLS-specific tool for the HRQoL evaluation of this population., (© 2023 The Authors. Arthritis Care & Research published by Wiley Periodicals LLC on behalf of American College of Rheumatology.)
- Published
- 2024
- Full Text
- View/download PDF
37. Organizational Learning in the Morbidity and Mortality Conference.
- Author
-
Batthish M, Kuper A, Fine C, Laxer RM, and Baker GR
- Subjects
- Humans, Prospective Studies, Patient Safety, Morbidity, Safety Management, Quality Improvement
- Abstract
Introduction: The focus of morbidity and mortality conferences (M&MCs) has shifted to emphasize quality improvement and systems-level care. However, quality improvement initiatives targeting systems-level errors are challenged by learning in M&MCs, which occurs at the individual attendee level and not at the organizational level. Here, we aimed to describe how organizational learning in M&MCs is optimized by particular organizational and team cultures., Methods: A prospective, multiple-case study design was used. Using purposive sampling, three cases covering different medical/surgical specialties in North America were chosen. Data collection included direct observations of the M&MC, semistructured interviews with key M&MC members, and documentary information., Results: The role of the M&MC in all cases integrated two key concepts: recognition of system-wide trends and learning from error, at an organizational and team level. All cases provided evidence of double-loop learning and used organizational memory strategies to ensure knowledge was retained within the organization. A patient safety culture was linked to the promotion of open communication, fostering learning from adverse events., Conclusion: This study describes three cases of systems-oriented M&MCs that reflected elements of organizational learning theory. The M&MC can therefore provide a context for organizational learning, allowing optimal learning from adverse events., Competing Interests: The authors have no conflicts of interest to declare., (Copyright © 2023 National Association for Healthcare Quality.)
- Published
- 2024
- Full Text
- View/download PDF
38. Characteristics and onset of presentation of pediatric stiff skin syndrome: A retrospective cohort study of 11 patients in a tertiary care center.
- Author
-
Sanchez-Espino LF, Sibbald C, Stimec J, Laxer RM, and Pope E
- Subjects
- Humans, Child, Retrospective Studies, Cohort Studies, Tertiary Care Centers, Skin Diseases, Genetic, Contracture
- Abstract
Background/objective: Stiff skin syndrome (SSS) is a rare disorder characterized by "rock hard" indurated skin affecting different body parts. The localized variant poses a diagnostic challenge, as it is frequently mistaken for other inflammatory connective tissue disorders. The aim of this study is to provide insightful clinical, radiologic and diagnostic data that might prove useful for the evaluation, management and treatment of pediatric patients with segmental SS., Methods: This single-center cohort study included patients ≤18 years diagnosed with localized SSS from 1988 to 2021 in a quaternary pediatric healthcare center in Toronto, Canada. Data included demographics, clinical, histopathologic and radiologic features, treatments, and clinical course. Data were summarized with descriptive statistics (mean, standard deviation, medians, interquartile ranges [IQRs]) and frequencies., Results: A total of 11 patients were included. The sclerotic changes were measured clinically and radiologically, by a total of 16 imaging studies: 13 magnetic resonance imaging (MRI) and 3 ultrasound. MRI readings showed abnormal high signal intensity of the affected tissue correlating with the anatomical site of involvement in all cases, specifically, in the shoulder/pelvic girdle with limb extension. Shear wave ultrasound elastography (SWE) demonstrated higher values within the dermis compared to the control site., Conclusion: The presence of segmental sclerotic changes that affects the pelvic/shoulder girdle with extension to the extremities, in the absence of inflammation on biopsy and abnormal signaling intensity on imaging is suggestive of SSS. Skin SWE is a feasible, noninvasive, and objective instrument to evaluate and monitor sclerotic changes overtime, it could be potentially extrapolated to other pediatric skin sclerotic conditions., (© 2023 Wiley Periodicals LLC.)
- Published
- 2024
- Full Text
- View/download PDF
39. Reactive Arthritis in Children: Case Report, Narrative Review and Proposed Therapy.
- Author
-
Alshaya M, Almutairi N, Alrasheed A, Albanaqi I, Laxer RM, and Alhammad A
- Subjects
- Humans, Child, Adolescent, Male, Female, Algorithms, Child, Preschool, Arthritis, Reactive drug therapy, Arthritis, Reactive diagnosis
- Abstract
Reactive arthritis is an acute inflammatory aseptic arthritis that is preceded by an infectious process in genetically predisposed individuals. It has been associated with gastrointestinal or genitourinary infection. Reactive arthritis is rare in children. In this review, we present two index cases that need biologic treatment followed by a thorough review of reactive arthritis in children and adolescents with proposed treatment algorithm., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)
- Published
- 2024
- Full Text
- View/download PDF
40. Pediatric Rheumatology Care and Outcomes Improvement Network's Quality Measure Set to Improve Care of Children With Juvenile Idiopathic Arthritis.
- Author
-
Bingham CA, Harris JG, Qiu T, Gilbert M, Vora SS, Yildirim-Toruner C, Ferraro K, Lovell DJ, Taylor J, Mannion ML, Weiss JE, Laxer RM, Shishov M, Oberle EJ, Gottlieb BS, Lee TC, Pan N, Burnham JM, Fair DC, Batthish M, Hazen MM, Spencer CH, and Morgan EM
- Subjects
- Humans, Child, Quality Indicators, Health Care, Outcome Assessment, Health Care, Arthritis, Juvenile therapy, Arthritis, Juvenile drug therapy, Rheumatology methods, Antirheumatic Agents therapeutic use
- Abstract
Objective: To describe the selection, development, and implementation of quality measures (QMs) for juvenile idiopathic arthritis (JIA) by the Pediatric Rheumatology Care and Outcomes Improvement Network (PR-COIN), a multihospital learning health network using quality improvement methods and leveraging QMs to drive improved outcomes across a JIA population since 2011., Methods: An American College of Rheumatology-endorsed multistakeholder process previously selected initial process QMs. Clinicians in PR-COIN and parents of children with JIA collaboratively selected outcome QMs. A committee of rheumatologists and data analysts developed operational definitions. QMs were programmed and validated using patient data. Measures are populated by registry data, and performance is displayed on automated statistical process control charts. PR-COIN centers use rapid-cycle quality improvement approaches to improve performance metrics. The QMs are revised for usefulness, to reflect best practices, and to support network initiatives., Results: The initial QM set included 13 process measures concerning standardized measurement of disease activity, collection of patient-reported outcome assessments, and clinical performance measures. Initial outcome measures were clinical inactive disease, low pain score, and optimal physical functioning. The revised QM set has 20 measures and includes additional measures of disease activity, data quality, and a balancing measure., Conclusion: PR-COIN has developed and tested JIA QMs to assess clinical performance and patient outcomes. The implementation of robust QMs is important to improve quality of care. PR-COIN's set of JIA QMs is the first comprehensive set of QMs used at the point-of-care for a large cohort of JIA patients in a variety of pediatric rheumatology practice settings., (© 2023 The Authors. Arthritis Care & Research published by Wiley Periodicals LLC on behalf of American College of Rheumatology.)
- Published
- 2023
- Full Text
- View/download PDF
41. Paediatric inflammatory multisystem syndrome in Canada: population-based surveillance and role of SARS-CoV-2 linkage.
- Author
-
El Tal T, Morin MP, Morris SK, Farrar DS, Berard RA, Kakkar F, Moore Hepburn C, Baerg K, Beaufils C, Bennett TL, Benseler SM, Beaudoin-Bussières G, Chan K, Cyr C, Dahdah N, Donner EJ, Drouin O, Edjoc R, Eljaouhari M, Embree JE, Farrell C, Finzi A, Forgie S, Giroux R, Kang KT, King M, Laffin Thibodeau M, Lang B, Laxer RM, Luu TM, McCrindle BW, Orkin J, Papenburg J, Pound CM, Price VE, Proulx-Gauthier JP, Purewal R, Sadarangani M, Salvadori MI, Thibeault R, Top KA, Viel-Thériault I, Haddad E, Scuccimarri R, and Yeung RSM
- Subjects
- Humans, Male, Child, Child, Preschool, Female, Canada epidemiology, Systemic Inflammatory Response Syndrome diagnosis, Systemic Inflammatory Response Syndrome epidemiology, SARS-CoV-2, COVID-19 epidemiology, COVID-19 therapy
- Abstract
Background: Paediatric inflammatory multisystem syndrome (PIMS) is a rare condition temporally associated with SARS-CoV-2 infection. Using national surveillance data, we compare presenting features and outcomes among children hospitalized with PIMS by SARS-CoV-2 linkage, and identify risk factors for intensive care (ICU)., Methods: Cases were reported to the Canadian Paediatric Surveillance Program by a network of >2800 pediatricians between March 2020 and May 2021. Patients with positive versus negative SARS-CoV-2 linkages were compared, with positive linkage defined as any positive molecular or serologic test or close contact with confirmed COVID-19. ICU risk factors were identified with multivariable modified Poisson regression., Results: We identified 406 children hospitalized with PIMS, including 49.8% with positive SARS-CoV-2 linkages, 26.1% with negative linkages, and 24.1% with unknown linkages. The median age was 5.4 years (IQR 2.5-9.8), 60% were male, and 83% had no comorbidities. Compared to cases with negative linkages, children with positive linkages experienced more cardiac involvement (58.8% vs. 37.4%; p < 0.001), gastrointestinal symptoms (88.6% vs. 63.2%; p < 0.001), and shock (60.9% vs. 16.0%; p < 0.001). Children aged ≥6 years and those with positive linkages were more likely to require ICU., Conclusions: Although rare, 30% of PIMS hospitalizations required ICU or respiratory/hemodynamic support, particularly those with positive SARS-CoV-2 linkages., Impact: We describe 406 children hospitalized with paediatric inflammatory multisystem syndrome (PIMS) using nationwide surveillance data, the largest study of PIMS in Canada to date. Our surveillance case definition of PIMS did not require a history of SARS-CoV-2 exposure, and we therefore describe associations of SARS-CoV-2 linkages on clinical features and outcomes of children with PIMS. Children with positive SARS-CoV-2 linkages were older, had more gastrointestinal and cardiac involvement, and hyperinflammatory laboratory picture. Although PIMS is rare, one-third required admission to intensive care, with the greatest risk amongst those aged ≥6 years and those with a SARS-CoV-2 linkage., (© 2023. The Author(s), under exclusive licence to the International Pediatric Research Foundation, Inc.)
- Published
- 2023
- Full Text
- View/download PDF
42. The Journal of Rheumatology : A Strong Supporter of Pediatric Rheumatology.
- Author
-
Laxer RM
- Published
- 2023
- Full Text
- View/download PDF
43. Lengthening sleep reduces pain in childhood arthritis: a crossover randomised controlled trial.
- Author
-
Clairman H, Dover S, Tomlinson G, Beebe D, Cameron B, Laxer RM, Levy D, Narang I, Paetkau S, Schneider R, Spiegel L, Stephens S, Stinson J, Tse S, Weiss S, Whitney K, and Feldman BM
- Subjects
- Adolescent, Child, Humans, Bayes Theorem, Chronic Disease, Health Status, Sleep, Cross-Over Studies, Arthritis, Juvenile complications, Chronic Pain
- Abstract
Objectives: Juvenile idiopathic arthritis (JIA) is a common chronic childhood disease and chronic pain is a debilitating feature. A strong link has been shown between poor sleep and pain in JIA. However, the causal direction is unknown. This study's aim was to determine if, in adolescents with JIA, a recommended healthful sleep duration leads to reductions in pain when compared with the restricted sleep (RS) duration that is commonly seen., Methods: Patients with JIA (12-18 years old; pain score of ≥1 on a visual analogue scale) participated in a randomised, crossover sleep manipulation protocol. The 3-week protocol comprised a baseline week (BL), a week with healthy sleep duration (HSD; 9.5 hours in bed/night) and a RS week (RS; 6.5 hours in bed/night). After BL, participants were randomly assigned to either HSD or RS, and then crossed over to the other condition. Pain was self-assessed using the iCanCope with Pain app. We used Bayesian hierarchical models to estimate the effect of sleep duration on pain., Results: Participants (n=31; mean age=15.0±1.8 years) averaged 1.4 (95% credible interval (CrI) 1.2-1.6) more hours of sleep per night during HSD relative to RS. Compared with RS, HSD resulted in a favourable effect on pain scores (OR 0.61, 95% CrI 0.39-0.95)., Conclusion: It is possible to have adolescents with childhood arthritis get a healthier sleep duration, and this longer sleep results in reduced pain. These findings complement prior correlational studies and confirm a causal relationship between reduced sleep duration and increased pain., Trial Registration Number: NCT04133662., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)
- Published
- 2023
- Full Text
- View/download PDF
44. Feasibility of Conducting Comparative Effectiveness Research and Validation of a Clinical Disease Activity Score for Chronic Nonbacterial Osteomyelitis.
- Author
-
Wu EY, Oliver M, Scheck J, Lapidus S, Akca UK, Yasin S, Stern SM, Insalaco A, Pardeo M, Simonini G, Marrani E, Wang X, Huang B, Kovalick LK, Rosenwasser N, Casselman G, Liau A, Shao Y, Yang C, Mosa DM, Tucker L, Girschick H, Laxer RM, Akikusa JD, Hedrich CM, Onel K, Dedeoglu F, Twilt M, Ferguson PJ, Ozen S, and Zhao Y
- Subjects
- Child, Young Adult, Humans, Feasibility Studies, Prospective Studies, Chronic Disease, Comparative Effectiveness Research, Osteomyelitis drug therapy, Osteomyelitis pathology
- Abstract
Objective: Prospective comparative effectiveness research (CER) in chronic nonbacterial osteomyelitis (CNO) is lacking. Our objectives were to (1) determine the use and safety of each consensus treatment plan (CTP) regimen for CNO, (2) assess the feasibility of using the Chronic Nonbacterial Osteomyelitis International Registry (CHOIR) data for CER, and (3) develop and validate a CNO clinical disease activity score (CDAS) using CHOIR., Methods: Consenting children or young adults with CNO were enrolled into CHOIR. Demographic, clinical, and imaging data were prospectively collected. The CNO CDAS was developed through a Delphi survey and nominal group technique. External validation surveys were administered to CHOIR participants., Results: One hundred forty (78.2%) CHOIR participants enrolled between August 2018 and September 2020 received at least 1 CTP regimen. Baseline characteristics from different CTP groups were well matched. Patient pain, patient global assessment, and clinical CNO lesion count were key variables included in the CNO CDAS. The CDAS showed a strong correlation with patient/parent report of difficulty using a limb, back, or jaw and patient/parent report of disease severity, but a weak correlation with patient/parent report of fatigue, sadness, and worry. The change in CDAS was significant in patients reporting disease worsening or improvement ( P < 0.001). The CDAS significantly decreased after initiating second-line treatments from median 12.0 (IQR 8.0-15.5) to 5.0 (IQR 3.0-12.0; P = 0.002). Although second-line treatments were well tolerated, psoriasis was the most common adverse event., Conclusion: The CNO CDAS was developed and validated for disease monitoring and assessment of treatment effectiveness. CHOIR provided a comprehensive framework for future CER., (Copyright © 2023 by the Journal of Rheumatology.)
- Published
- 2023
- Full Text
- View/download PDF
45. SARS-CoV-2 infection in technology-dependent children: a multicenter case series.
- Author
-
Robinson J, Dewan T, Morris SK, Bitnun A, Gill P, Tal TE, Laxer RM, Yeh EA, Yea C, Ulloa-Gutierrez R, Brenes-Chacon H, Yock-Corrales A, Ivankovich-Escoto G, Soriano-Fallas A, Mezerville MH, Papenburg J, Lefebvre MA, Nateghian A, Aski BH, Manafi A, Dwilow R, Bullard J, Cooke S, Restivo L, Lopez A, Sadarangani M, Roberts A, Le Saux N, Bowes J, Purewal R, Lautermilch J, Wong JK, Piche D, Top KA, Foo C, Panetta L, Merckx J, and Barton M
- Subjects
- Humans, Child, SARS-CoV-2, Canada, Disease Progression, Oxygen, COVID-19
- Abstract
Purpose: The objective of this study was to describe the clinical course and outcomes in children with technology dependence (TD) hospitalized with SARS-CoV-2 infection., Methods: Seventeen pediatric hospitals (15 Canadian and one each in Iran and Costa Rica) included children up to 17 years of age admitted February 1, 2020, through May 31, 2021, with detection of SARS-CoV-2. For those with TD, data were collected on demographics, clinical course and outcome., Results: Of 691 children entered in the database, 42 (6%) had TD of which 22 had feeding tube dependence only, 9 were on supplemental oxygen only, 3 had feeding tube dependence and were on supplemental oxygen, 2 had a tracheostomy but were not ventilated, 4 were on non-invasive ventilation, and 2 were on mechanical ventilation prior to admission. Three of 42 had incidental SARS-CoV-2 infection. Two with end-stage underlying conditions were transitioned to comfort care and died. Sixteen (43%) of the remaining 37 cases required increased respiratory support from baseline due to COVID-19 while 21 (57%) did not. All survivors were discharged home., Conclusion: Children with TD appear to have an increased risk of COVID-19 hospitalization. However, in the absence of end-stage chronic conditions, all survived to discharge., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany.)
- Published
- 2023
- Full Text
- View/download PDF
46. Gathering expert consensus to inform a proposed trial in chronic nonbacterial osteomyelitis (CNO).
- Author
-
Hedrich CM, Beresford MW, Dedeoglu F, Hahn G, Hofmann SR, Jansson AF, Laxer RM, Miettunen P, Morbach H, Pain CE, Ramanan AV, Roberts E, Schnabel A, Theos A, Whitty L, Zhao Y, Ferguson PJ, and Girschick HJ
- Subjects
- Child, Adolescent, Humans, Consensus, Cytokines, Pain complications, Pain drug therapy, Chronic Disease, Antirheumatic Agents therapeutic use, Osteomyelitis drug therapy
- Abstract
Chronic nonbacterial osteomyelitis (CNO) is an autoinflammatory bone disease that primarily affects children and adolescents. CNO is associated with pain, bone swelling, deformity, and fractures. Its pathophysiology is characterized by increased inflammasome assembly and imbalanced expression of cytokines. Treatment is currently based on personal experience, case series and resulting expert recommendations. Randomized controlled trials (RCTs) have not been initiated because of the rarity of CNO, expired patent protection of some medications, and the absence of agreed outcome measures. An international group of fourteen CNO experts and two patient/parent representatives was assembled to generate consensus to inform and conduct future RCTs. The exercise delivered consensus inclusion and exclusion criteria, patent protected (excludes TNF inhibitors) treatments of immediate interest (biological DMARDs targeting IL-1 and IL-17), primary (improvement of pain; physician global assessment) and secondary endpoints (improved MRI; improved PedCNO score which includes physician and patient global scores) for future RCTs in CNO., Competing Interests: Declaration of Competing Interest In the past, CMH received research funding from Novartis for research in psoriasis (secukinumab programme, 2017–2019). In the past 5 years, CMH received speaker's honoraria from Roche, and was involved in advisory boards hosted by Novartis and Cancer Research UK (CRUK). CMH, PJF, HJG, and YZ participated in advisory boards on the use of canakinumab in inflammatory bone disease hosted by Novartis. RML is a consultant to Novartis and SOBI., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)
- Published
- 2023
- Full Text
- View/download PDF
47. Finding a Quorum in Deficiency of Adenosine Deaminase 2 Management.
- Author
-
Tsoukas P and Laxer RM
- Subjects
- Humans, Erythrocytes, Adenosine Deaminase genetics, Intercellular Signaling Peptides and Proteins
- Published
- 2023
- Full Text
- View/download PDF
48. Case report: Novel variants in RELA associated with familial Behcet's-like disease.
- Author
-
An JW, Pimpale-Chavan P, Stone DL, Bandeira M, Dedeoglu F, Lo J, Bohnsack J, Rosenzweig S, Schnappauf O, Dissanayake D, Hiraki LT, Kastner DL, Pelajo C, Laxer RM, and Aksentijevich I
- Subjects
- Humans, Genetic Testing, Inflammation genetics, Signal Transduction genetics, Transcription Factor RelA genetics, Transcription Factor RelA metabolism, NF-kappa B metabolism, Behcet Syndrome drug therapy, Behcet Syndrome genetics
- Abstract
RELA haploinsufficiency is a recently described autoinflammatory condition presenting with intermittent fevers and mucocutaneous ulcerations. The RELA gene encodes the p65 protein, one of five NF-κB family transcription factors. As RELA is an essential regulator of mucosal homeostasis, haploinsufficiency leads to decreased NF-κB signaling which promotes TNF-driven mucosal apoptosis with impaired epithelial recovery. Thus far, only eight cases have been reported in the literature. Here, we report four families with three novel and one previously described pathogenic variant in RELA. These four families included 23 affected individuals for which genetic testing was available in 16. Almost half of these patients had been previously diagnosed with more common rheumatologic entities (such as Behcet's Disease; BD) prior to the discovery of their pathogenic RELA variants. The most common clinical features were orogenital ulcers, rash, joint inflammation, and fever. The least common were conjunctivitis and recurrent infections. Clinical variability was remarkable even among familial cases, and incomplete penetrance was observed. Patients in our series were treated with a variety of medications, and benefit was observed with glucocorticoids, colchicine, and TNF inhibitors. Altogether, our work adds to the current literature and doubles the number of reported cases with RELA-Associated Inflammatory Disease (RAID). It reaffirms the central importance of the NF-κB pathway in immunity and inflammation, as well as the important regulatory role of RELA in mucosal homeostasis. RELA associated inflammatory disease should be considered in all patients with BD, particularly those with early onset and/or with a strong family history., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 An, Pimpale-Chavan, Stone, Bandeira, Dedeoglu, Lo, Bohnsack, Rosenzweig, Schnappauf, Dissanayake, Hiraki, Kastner, Pelajo, Laxer and Aksentijevich.)
- Published
- 2023
- Full Text
- View/download PDF
49. Evaluation of Methotrexate Intolerance in Children With Morphea.
- Author
-
McColl J, Laxer RM, Pope E, and Sibbald C
- Abstract
Objective: Methotrexate is an immunosuppressant commonly used in dermatology. The prevalence of intolerance using the Methotrexate Intolerance Severity Score (MISS) in pediatric juvenile idiopathic arthritis (JIA) ranges from 25% to 75%, but studies in morphea patients are lacking. We sought to determine the prevalence and predictors of methotrexate intolerance in children with morphea compared with children with inflammatory skin diseases and JIA/uveitis., Methods: Eligible patients were ages 2 to 18 years and were taking methotrexate for at least 3 months to treat morphea, inflammatory skin disease, or uveitis/JIA. Methotrexate intolerance was calculated using the MISS. A 1-way analysis of variance compared absolute intolerance scores. Multivariate regression analysis was used to compare MISS across diseases and covariates., Results: Of 48 participants (mean ± SD age, 11.3 ± 4.1 years, 70.8% female), 15 had morphea, 16 had JIA/uveitis, and 17 had inflammatory skin diseases. The overall prevalence of intolerance was 20.8%. Age, sex, duration, and dose did not correlate with overall MISS. The MISS mean ± SD total for oral dosing was 2.5 ± 3.4, compared with 6.78 ± 6.8 for subcutaneous dosing. Patients with JIA/uveitis had the highest prevalence of intolerance (37.5%, n = 6), followed by morphea patients (20%, n = 3) and inflammatory skin disease patients (5.9%, n = 1). The OR of intolerance according to route of administration was 11.2 (95% CI, 2.03-61.89)., Conclusions: Methotrexate intolerance was highest among patients with JIA/uveitis. The only predictor for risk of intolerance was subcutaneous route of administration. Future work could examine disease activity correlations and interventions designed to minimize intolerance., Competing Interests: Disclosures. The authors declare no conflict or financial interest in any product or service mentioned in the manuscript including grants, equipment, medications, employment, gifts, and honoraria. The authors had full access to all the data in the study and take responsibility for the integrity of the data and accuracy of the data analysis., (Copyright. Pediatric Pharmacy Association. All rights reserved. For permissions, email: membership@pediatricpharmacy.org.)
- Published
- 2023
- Full Text
- View/download PDF
50. The 2021 EULAR/American College of Rheumatology Points to Consider for Diagnosis, Management and Monitoring of the Interleukin-1 Mediated Autoinflammatory Diseases: Cryopyrin-Associated Periodic Syndromes, Tumour Necrosis Factor Receptor-Associated Periodic Syndrome, Mevalonate Kinase Deficiency, and Deficiency of the Interleukin-1 Receptor Antagonist.
- Author
-
Romano M, Arici ZS, Piskin D, Alehashemi S, Aletaha D, Barron K, Benseler S, Berard RA, Broderick L, Dedeoglu F, Diebold M, Durrant K, Ferguson P, Foell D, Hausmann JS, Jones OY, Kastner D, Lachmann HJ, Laxer RM, Rivera D, Ruperto N, Simon A, Twilt M, Frenkel J, Hoffman HM, de Jesus AA, Kuemmerle-Deschner JB, Ozen S, Gattorno M, Goldbach-Mansky R, and Demirkaya E
- Subjects
- Child, Preschool, Fever, Humans, Interleukin 1 Receptor Antagonist Protein therapeutic use, Interleukin-1, Quality of Life, Receptors, Interleukin-1, United States, Cryopyrin-Associated Periodic Syndromes diagnosis, Cryopyrin-Associated Periodic Syndromes drug therapy, Hereditary Autoinflammatory Diseases diagnosis, Hereditary Autoinflammatory Diseases drug therapy, Hereditary Autoinflammatory Diseases genetics, Mevalonate Kinase Deficiency diagnosis, Mevalonate Kinase Deficiency drug therapy, Rheumatology
- Abstract
Background: The interleukin-1 (IL-1) mediated systemic autoinflammatory diseases, including the cryopyrin- associated periodic syndromes (CAPS), tumour necrosis factor receptor-associated periodic syndrome (TRAPS), mevalonate kinase deficiency (MKD) and deficiency of the IL-1 receptor antagonist (DIRA), belong to a group of rare immunodysregulatory diseases that primarily present in early childhood with variable multiorgan involvement. When untreated, patients with severe clinical phenotypes have a poor prognosis, and diagnosis and management of these patients can be challenging. However, approved treatments targeting the proinflammatory cytokine IL-1 have been life changing and have significantly improved patient outcomes., Objective: To establish evidence-based recommendations for diagnosis, treatment and monitoring of patients with IL-1 mediated autoinflammatory diseases to standardise their management., Methods: A multinational, multidisciplinary task force consisting of physician experts, including rheumatologists, patients or caregivers and allied healthcare professionals, was established. Evidence synthesis, including systematic literature review and expert consensus (Delphi) via surveys, was conducted. Consensus methodology was used to formulate and vote on statements to guide optimal patient care., Results: The task force devised five overarching principles, 14 statements related to diagnosis, 10 on therapy, and nine focused on long-term monitoring that were evidence and/or consensus-based for patients with IL-1 mediated diseases. An outline was developed for disease-specific monitoring of inflammation-induced organ damage progression and reported treatments of CAPS, TRAPS, MKD and DIRA., Conclusion: The 2021 EULAR/American College of Rheumatology points to consider represent state-of-the-art knowledge based on published data and expert opinion to guide diagnostic evaluation, treatment and monitoring of patients with CAPS, TRAPS, MKD and DIRA, and to standardise and improve care, quality of life and disease outcomes., (© 2022 American College of Rheumatology. This article has been contributed to by U.S. Government employees and their work is in the public domain in the USA.)
- Published
- 2022
- Full Text
- View/download PDF
Catalog
Discovery Service for Jio Institute Digital Library
For full access to our library's resources, please sign in.