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Background:The cardiovascular (CV) safety of non-steroidal anti-inflammatory drugs (NSAIDs) and selective cyclooxygenase-2 inhibitors has been the subject of considerable debate.Objective:The objective of this study was to determine the risk of CV events with lumiracoxib by meta-analysis of all completed, randomized controlled trials (RCTs) of >/=1 week and up to 1 year in duration of patients with osteoarthritis and rheumatoid arthritis.Methods:The Novartis Lumiracoxib Clinical Trial Database, which includes all clinical studies conducted to date with lumiracoxib, was reviewed. Data were extracted from RCTs of >/=1 week and up to 1 year in duration, the maximum study duration; 34,668 patients were included in standard and cumulative meta-analyses. Twenty-two RCTs of lumiracoxib 100 to 1200 mg daily were identified; 22,781 patients were included in 1-year trials. Mean age of the patients was 61.5 years and 74% were female. More than 50% of the patients in these studies had hypertension at baseline and 6% had diabetes. Parameters analyzed were the Antiplatelet Trialists' Collaboration (APTC) composite CV end point of myocardial infarction (MI), stroke (ischemic and hemorrhagic), and CV death; MI alone; and stroke alone. Twenty-one of the 22 RCTs have been published.Results:For all 3 parameters, relative risk (RR) was calculated versus non-naproxen NSAIDs, naproxen, and placebo. The results were as follows: for the APTC end point versus non-naproxen NSAIDs: RR 0.83, 95% CI, 0.46-1.51; versus naproxen: RR 1.49, 95% CI, 0.94-2.36; versus placebo: RR 1.08, 95% CI, 0.41-2.86; for MI alone versus non-naproxen NSAIDs: RR 0.80, 95% CI, 0.28-2.25; versus naproxen: RR 1.69, 95% CI, 0.82-3.48; versus placebo: RR 1.27, 95% CI, 0.25-6.56; and for stroke alone versus non-naproxen NSAIDs: RR 0.91, 95% CI, 0.35-2.35; versus naproxen: RR 1.42, 95% CI, 0.70-2.91; versus placebo: RR 0.59, 95% CI, 0.13-2.74. Cumulative meta-analyses of lumiracoxib versus all comparators (placebo, diclofenac, ibuprofen, celecoxib, rofecoxib, and naproxen) did not find any significant differences in APTC, MI alone, or stroke alone.Conclusion:This meta-analysis of 34,668 patients receiving >/=1 week and up to 1 year of treatment found no evidence that lumiracoxib was associated with a significant increase in CV risk compared with naproxen, placebo, or all comparators (placebo, diclofenac, ibuprofen, celecoxib, rofecoxib, and naproxen). [ABSTRACT FROM AUTHOR]

BACKGROUND: Lumiracoxib is a cyclooxygenase-2-selective inhibitor developed for the treatment of osteoarthritis (OA), rheumatoid arthritis, and acute pain. OBJECTIVES: This study assessed the efficacy and tolerability of lumiracoxib 100 mg QD compared with celecoxib and placebo in patients with OA of the knee. METHODS: In this 13-week, double-blind, double-dummy,placebo-controlled, parallel-group study, patients with primary OA of the knee and pain intensity in the target knee a 40 mm on a 100-mm visual analog scale after a 3- to 7-day washout of nonsteroidal anti-inflammatory drugs were randomized to receive lumiracoxib 100 mg QD, lumiracoxib 100 mg QD with a loading dose of lumiracoxib 200 mg QD for the first 2 weeks, celecoxib 200 mg QD, or placebo. Three primary efficacy variables were assessed at the end of the study: pain intensity in the target knee, the patient's global assessment of disease activity, and functional status (Western Ontario and McMaster Universities Osteoarthritis Index total score). In addition, the treatment response was assessed using the Outcome Measures in Clinical Trials-Osteoarthritis Research Society International (OMERACT OARSI) criteria. The safety profile and tolerability of all treatments were also examined. RESULTS: The study enrolled 1551 patients (primarily white; 62% female; mean age, 60.5 years): 391 were randomized to receive lumiracoxib 100 mg QD, 385 lumiracoxib 100 mg QD with a loading dose, 393 celecoxib 200 mg QD, and 382 placebo. Treatment groups were closely balanced at baseline with respect to demographic and disease characteristics. Lumiracoxib was superior to placebo (P < 0.001) and similar to celecoxib on all primary efficacy variables. Reductions in pain intensity in the target knee were similar in the 2 lumiracoxib groups at week 13 (estimated least square mean difference vs placebo: -6.7 and -8.1 mm for lumiracoxib 100 mg QD and lumiracoxib 100 mg QD with loading dose, respectively; both, P < 0.001); with celecoxib, the estimated least square mean difference was -5.7 mm (P < 0.001). Significant differences compared with placebo were seen in all variables starting at week 2 for all active treatments (all, P < 0.001). No significant differences were seen between the lumiracoxib groups at any time point. Based on OMERACT OARSI criteria, all active treatments were superior to placebo (all, P < 0.001). Lumiracoxib and celecoxib were well tolerated, with an incidence of adverse events similar to that with placebo (64.7% lumiracoxib 100 mg QD, 67.0% lumiracoxib 100 mg QD with loading dose, 58.8% celecoxib, 58.4% placebo). CONCLUSION: In this population of patients with OA of the knee, lumiracoxib 100 mg QD was of similar efficacy to celecoxib 200 mg QD and had similar tolerability to placebo. [ABSTRACT FROM AUTHOR]

Mrs. Ellis (a pseudonym) is a 57-year-old woman with a 10-year history of rheumatoid arthritis (RA) and a previous episode of transverse myelitis with residual pain and weakness.After the patient's insufficient response to methotrexate (MTX) and upon realizing that tumor necrosis factor inhibitors are relatively contraindicated in demyelinating disease, I wrote a prescription for abatacept (ABA), which could conceivably help both her RA and her transverse myelitis.

Objective: To describe patients' use of opioids in the year preceding and year following new diagnosis of ankylosing spondylitis (AS), psoriatic arthritis (PsA), or rheumatoid arthritis (RA), compared with patients without the/se diseases., Methods: This study used US IBM ® MarketScan ® Commercial Claims and Encounters (CCAE) and Medicaid data and included three cohorts, comprised of incident cases of AS, PsA, or RA (2010-2017). Three matched comparator patients (without the incident disease) were selected for each patient within the disease cohort. Opioid use and appropriate treatment exposure (as defined by US guideline recommendations) in the 12-month baseline and follow-up periods were evaluated using descriptive analyses., Results: Prevalence of claims for opioids was higher for disease cohorts vs. comparators in CCAE; 36.4% of patients with AS, 29.5% with PsA, and 44.4% with RA did not have any claim for guideline-appropriate therapy in follow-up. Prevalence of claims for opioids was also higher for disease cohorts vs. comparators in Medicaid; 30.6% of patients with AS, 36.6% with PsA, and 65.4% with RA did not have any claim for guideline-appropriate therapy in follow-up., Conclusions: In patients with AS, PsA, or RA, there was high reliance on opioids at and around the time of diagnosis. Significant proportions of patients were not on appropriate treatment as defined by professional society post-diagnosis guidelines; this discordance between actual patient therapies and treatment recommendations may suggest a need for better awareness of appropriate pain management and treatment strategies in rheumatic diseases. Key Points • This study analysed opioid use among patients with ankylosing spondylitis (AS), psoriatic arthritis (PsA), or rheumatoid arthritis (RA), and adds to current knowledge by expanding beyond assessment of opioid use at diagnosis, to the year before and after diagnosis. • Opioid use was found to be highly prevalent in AS, PsA, and RA in the year prior to diagnosis and, interestingly, was still seen during the year after diagnosis. • Opioids are neither disease modifying, nor a targeted/recommended treatment for chronic autoimmune diseases. In addition to their association with significant economic costs, opioids are potentially hazardous and are not better than alternative treatments with superior safety profiles. • The reasons behind opioid prescribing patterns should be explored further to support movement to targeted therapies., (© 2024. The Author(s).)

Objective: To gain consensus on the definitions and descriptions of the domains of the Outcome Measures in Rheumatology (OMERACT) core domain set for rheumatology trials evaluating shared decision making (SDM) interventions., Methods: Following the OMERACT Handbook methods, our Working Group (WG), comprised of 90 members, including 17 patient research partners (PRPs) and 73 clinicians and researchers, had six virtual meetings in addition to email exchanges to develop draft definitions and descriptions. The WG then conducted an international survey of its members to gain consensus on the definitions and descriptions. Finally, the WG members had virtual meetings and e-mail exchanges to review survey results and finalize names, definitions and descriptions of the domains., Results: WG members contributed to developing the definitions. Fifty-two members representing four continents and 13 countries completed the survey, including 15 PRPs, 33 clinicians and 37 researchers. PRPs and clinicians/researchers agreed with all definitions and descriptions with agreements ranging from 87% to 100%. Respondents suggested wording changes to the names, definitions and descriptions to better reflect the domains. Discussions led to further simplification and clarification to address common questions/concerns about the domains., Conclusion: Our WG reached consensus on the definitions and descriptions of the domains of the core domain set for rheumatology trials of SDM interventions. This step is crucial to understand each domain and provides the foundation to identify instruments to measure each domain for inclusion in the Core Outcome Measurement Set., Clinical Significance: The current study provides consensus-based definitions and descriptions for the domains of the OMERACT core domain set for shared decision making interventions from patients/caregivers, clinicians and researchers. This is a crucial step to understand each domain and provides the foundation to identify instruments to measure each domain for inclusion in the Core Outcome Measurement Set for trials of SDM interventions., Competing Interests: Declaration of competing interest Karine Toupin-April, Simon Décary, Maarten de Wit, Florian Naye, Alexa Meara, Jennifer L. Barton, Liana Fraenkel, Linda C. Li, Peter Brooks, Beverley Shea, Dawn Stacey, Cathie Hofstetter, Marieke Voshaar, Maria E. Suarez-Almazor, Tanya Meade, Janet Elizabeth Jull, Willemina Campbell, Rieke Alten, Esi M. Morgan, Ayano Kelly, Lara J. Maxwell, Francis Guillemin, Dorcas Beaton, Yasser El-Miedany, Shikha Mittoo, Tiffany Westrich Robertson, Susan J. Bartlett, Melissa Mannion, Samah Ismail Nasef, Adewale Adebajo, Laurent Arnaud, Tiffany K. Gill, Ellen Moholt, Jennifer Burt, Aruni Jayatilleke, Ihsane Hmamouchi, David Carrott, Kate Mather, Ajesh Maharaj, Saurab Sharma, Francesco Caso, Christopher Fong, Allyson Jones, Regina Greer-Smith, Akpabio Akpabio, Valerie Umaefulam, Sara Monti, Grayson Schultz, Rebecca R. Lee, Glen Stewart Hazlewood, Claire E.H. Barber, Dorthe B. Berthelsen, Laure Gossec, Sabrina May Nielsen, Sabrina Cavallo, Sonam Kiwalkar, Hemalatha Srinivasalu, Deb Constien, Vicki Evans and Peter Tugwell have nothing to disclose. Anne Boel is employed by UCB Pharma, B.V. Netherlands. Simon Stones is employed by Envision Pharma Group, Wilmslow, UK. Robin Christensen reports other potential COI from Lecture: Research Methods (Pfizer, DK; 2017), other from Lecture: GRADE Lecture (Celgene, DK; 2017), other from Ad Board Lecture: CAM (Orkla Health, DK; 2017), other from Project Grant: "GreenWhistle" (Mundipharma, 2019), other from Lecture: Diet in RMD (Novartis, DK; 2019), other from Consultancy Report: Network MA's (Biogen, DK; 2017), other from Ad Board Lecture: GRADE (Lilly, DK; 2017), other from Consultancy Report: GRADE (Celgene, 2018), other from Lecture: Network MA's (LEO; 2020), outside the submitted work; and Musculoskeletal Statistics Unit, The Parker Institute is grateful for the financial support received from public and private foundations, companies and private individuals over the years. The Parker Institute is supported by a core grant from the Oak Foundation; The Oak Foundation is a group of philanthropic organizations that, since its establishment in 1983, has given grants to not-for-profit organizations around the world. Annelies Boonen reports grants from Abbvie, grants from Celgene, other from UCB, other from Galapagos, other from Eli Lilly, outside the submitted work. Lyn March reports personal fees from Pfizer Australia, personal fees from Abbvie Australia, grants from Janssen Australia, outside the submitted work; Dr March is a member of OMERACT executive that receives arms-length funding from 9 companies. Willemina Campbell received OMERACT funded travel to a conference to attend meetings in regard to this paper. Jasvinder Singh reports personal fees from Crealta/Horizon, Medisys, Fidia, UBM LLC, Trio health, Medscape, WebMD, Adept Field Solutions, Clinical Care options, Clearview healthcare partners, Putnam associates, Focus forward, Navigant consulting, Spherix, Practice Point communications, the National Institutes of Health and the American College of Rheumatology, personal fees from Simply Speaking, other from Vaxart pharmaceuticals and Charlotte's Web Holdings (current); Amarin, Viking, and Moderna (previously owned), non-financial support from FDA Arthritis Advisory Committee, non-financial support from Steering committee of OMERACT, an international organization that develops measures for clinical trials and receives arms’ length funding from 12 pharmaceutical companies, non-financial support from Veterans Affairs Rheumatology Field Advisory Committee, non-financial support from Editor and the Director of the UAB Cochrane Musculoskeletal Group Satellite Center on Network Meta-analysis, outside the submitted work. Francisco J. Blanco reports grants from Gedeon Richter Plc., Bristol-Myers Squibb International Corporation (BMSIC), Sun Pharma Global FZE, Celgene Corporation, Janssen Cilag International N.V, Janssen Research & Development, Viela Bio, Inc., Astrazeneca AB, UCB BIOSCIENCES GMBH, UCB BIOPHARMA SPRL, AbbVie Deutschland GmbH & Co.KG, Merck KGaA, Amgen, Inc., Novartis Farmacéutica, S.A., Boehringer Ingelheim España, S.A, CSL Behring, LLC, Glaxosmithkline Research & Development Limited, Pfizer Inc, Lilly S.A., Corbus Pharmaceuticals Inc., Biohope Scientific Solutions for Human Health S.L., Centrexion Therapeutics Corp., Sanofi, MEIJI FARMA S.A., Kiniksa Pharmaceuticals, Ltd. Grunenthal, Asofarma Mexico, Gebro Pharma, Roche, Galapagos, Regeneron; outside the submitted work. Anthony P. Fernandez reports personal fees and other from AbbVie, grants, personal fees and other from Novartis, grants, personal fees and other from Mallinkrodt, other from Corbus, other from Pfizer, outside the submitted work. Sarah Mackie reports: Consultancy on behalf of her institution for Roche/Chugai, Sanofi, AbbVie, AstraZeneca, Pfizer; Investigator on clinical trials for Sanofi, GSK, Sparrow; speaking/lecturing on behalf of her institution for Roche/Chugai, Vifor, Pfizer, UCB, Novartis and AbbVie; chief investigator on STERLING-PMR trial, funded by NIHR; patron of the charity PMRGCAuk. No personal remuneration was received for any of the above activities. Support from Roche/Chugai to attend EULAR2019 in person and from Pfizer to attend ACR Convergence 2021 virtually. She is supported in part by the NIHR Leeds Biomedical Research Centre. The views expressed in this article are those of the authors and not necessarily those of the NIHR, the NIHR Leeds Biomedical Research Centre, the National Health Service or the UK Department of Health and Social Care. Elena Nikiphorou reports personal fees and other from AbbVie, personal fees and other from Eli-Lilly, personal fees and other from Gilead, personal fees and other from Celltrion, personal fees and other from Pfizer, other from Sanofi, outside the submitted work. Victor S. Sloan reports and paid consultant to various pharmaceutical companies and healthcare consultancies providing advice on clinical research and advisory committee preparation outside the scope of the submitted work. He is a shareholder in UCB Pharma. He is in the Peace Corps. This is his personal work, and does not reflect the opinion of the Peace Corps or the United States Government. Vibeke Strand reports consulting fees from AbbVie, Amgen, Arena, AstraZeneca, BMS, Boehringer Ingelheim, Celltrion, CORRONA, Crescendo/Myriad, Equillium, Genentech/Roche, GSK, Horizon, Inmedix, Janssen, Eli Lilly, Novartis, Pfizer, Regeneron Pharmaceuticals Inc., Samsung, Sandoz, Sanofi, TwoXAR and UCB, outside the submitted work. Esi M. Morgan reports grant support from Agency for Healthcare Research and Quality and Pfizer., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Objectives: Shared decision making (SDM) is a central tenet in rheumatic and musculoskeletal care. The lack of standardization regarding SDM instruments and outcomes in clinical trials threatens the comparative effectiveness of interventions. The Outcome Measures in Rheumatology (OMERACT) SDM Working Group is developing a Core Outcome Set for trials of SDM interventions in rheumatology and musculoskeletal health. The working group reached consensus on a Core Outcome Domain Set in 2020. The next step is to develop a Core Outcome Measurement Set through the OMERACT Filter 2.2., Methods: We conducted a scoping review (PRISMA-ScR) to identify candidate instruments for the OMERACT Filter 2.2 We systematically reviewed five databases (Ovid MEDLINE®, Embase, Cochrane Library, CINAHL and Web of Science). An information specialist designed search strategies to identify all measurement instruments used in SDM studies in adults or children living with rheumatic or musculoskeletal diseases or their important others. Paired reviewers independently screened titles, abstracts, and full text articles. We extracted characteristics of all candidate instruments (e.g., measured construct, measurement properties). We classified candidate instruments and summarized evidence gaps with an adapted version of the Summary of Measurement Properties (SOMP) table., Results: We found 14,464 citations, read 239 full text articles, and included 99 eligible studies. We identified 220 potential candidate instruments. The five most used measurement instruments were the Decisional Conflict Scale (traditional and low literacy versions) (n=38), the Hip/Knee-Decision Quality Instrument (n=20), the Decision Regret Scale (n=9), the Preparation for Decision Making Scale (n=8), and the CollaboRATE (n=8). Only 44 candidate instruments (20%) had any measurement properties reported by the included studies. Of these instruments, only 57% matched with at least one of the 7-criteria adapted SOMP table., Conclusion: We identified 220 candidate instruments used in the SDM literature amongst people with rheumatic and musculoskeletal diseases. Our classification of instruments showed evidence gaps and inconsistent reporting of measurement properties. The next steps for the OMERACT SDM Working Group are to match candidate instruments with Core Domains, assess feasibility and review validation studies of measurement instruments in rheumatic diseases or other conditions. Development and validation of new instruments may be required for some Core Domains., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Anthony P. Fernandez, MD, PhD: Past 36 months: Grants or contracts from any entity: Mallinckrodt, Novartis, Pfizer. Payments to institution and (partial) to me. Consulting fees: AbbVie, Biogen, UCB, BMS, Alexion: Payments to me. Payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events: AbbVie, BMS, Kyowa Kirin, Mallinckrodt: Payments to me. Leadership or fiduciary role in other board, society, committee or advocacy group, paid or unpaid: Board of Directors, American Society of Dermatopathology; Associate Editor, Journal of the American Academy of Dermatology. Arundathi Jayatilleke: Pas 36 months: Leadership or fiduciary role in other board, society, committee or advocacy group, paid or unpaid: Pennsylvania Rheumatology Society, board member: unpaid. Claire Barber: Pas 36 months: Grants or contracts from any entity: CIHR – 3: Peer reviewed national funding unrelated to current project. CIORA (Canadian Rheumatology Association): Peer reviewed national funding unrelated to current project. Cumming school of medicine Seed Grant: Local university funding, peer reviewed, unrelated to current project. Leadership or fiduciary role in other board, society, committee or advocacy group, paid or unpaid: Past chair Human Resource Committee, Canadian Rheumatology Association: Unrelated to current project. Dorcas Beaton: Past 36 months: Support for attending meetings and/or travel: OMERACT Management Team: OMERACT covers travel costs for members of management team to attend conferences on behalf of OMERACT. Leadership or fiduciary role in other board, society, committee or advocacy group, paid or unpaid: Member of Management team of OMERACT, chair of methodology at OMERACT: I help make decisions on the methods that will be used to come to a decision about core outcome sets at OMERACT. This would have informed methods used in this paper. Dorthe B Berthelsen: Past 36 months: Grants or contracts from any entity: Have received PhD Scholarships from Odense University Hospital and from the Faculty of Health Sciences, University of Southern Denmark. Support for attending meetings and/or travel: Have received a grant from the Erna Hamilton Foundation to cover meeting registration fee and travel costs for OMERACT 2023. Dawn Stacey: Past 36 months: Grants or contracts from any entity: Canadian Institutes of Health Research. Support for attending meetings and/or travel: Beijing University of Chinese Medicine – August 2023. Leadership or fiduciary role in other board, society, committee or advocacy group, paid or unpaid: Co-Chair International Patient Decision Aid Standards Collaboration (unpaid). Karine Toupin-April: Past 36 months: Support for attending meetings and/or travel: OMERACT travel award given to the Shared decision making group to help attend the OMERACT 2023 meeting. Lyn MARCH: Past 36 months: Grants or contracts from any entity: Commonwealth Government of Australia Medical Research Future Fund: RCT for biological tapering in RA and PsA (Utilising shared decision making): Payment to institution. Leadership or fiduciary role in other board, society, committee or advocacy group, paid or unpaid: Chair, Australian Rheumatology Association Research Fund Committee: unpaid. Executive, Global Alliance for MSK Health: unpaid. Maria Suarez-Almazor: Past 36 months: Consulting fees: Pfizer: Consultant. Eli Lilly: Consultant. Syneos Health: Consultant. Participation on a Data Safety Monitoring Board or Advisory Board: Celgene: DSMB member. Maarten de Wit: Past 36 months: Consulting fees: UCB: Payment to Stichting Tools, Netherlands. Peter Tugwell: Past 36 months: Consulting fees: Reformulary Group: Providing independent medical consultation professional services to the firms listed in this section. Participation on a Data Safety Monitoring Board or Advisory Board: UCB Biopharma GmbH & SPRL, Parexel International, Prahealth Sciences: An independent Committee Member for clinical trial Data Safety Monitoring Boards for FDA approved trials being conducted by:  - UCB Biopharma GmbH & SPRL, - Parexel International, - Prahealth Sciences. Other financial or non-financial interests: Abbvie, Astra Zeneca, Aurinia, BMS, Centrexion, GSK, Horizon Pharma Inc, Janssen, Novartis, Pfizer & Sparrow: I am [unpaid] Chair of the Management Group of a registered non-profit independent medical research organization, OMERACT, whose goal is to improve and advance the health outcomes for patients suffering from musculoskeletal conditions. OMERACT receives arms-length funding from 11 companies. Rieke Alten: Past 36 months: Consulting fees: Abbvie, BMS, CELLTRION; Eli Lilly; Galapagos, Janssen, Lilly, Novartis, Pfizer, Roche, UCB, Viatris. Payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events: Abbvie, BMS, CELLTRION; Eli Lilly; Galapagos, Janssen, Lilly, Novartis, Pfizer, Roche, UCB, Viatris. Support for attending meetings and/or travel: Abbvie, BMS, CELLTRION; Eli Lilly; Galapagos, Janssen, Lilly, Novartis, Pfizer, Roche, UCB, Viatris. Participation on a Data Safety Monitoring Board or Advisory Board: Abbvie, BMS, CELLTRION; Eli Lilly; Galapagos, Janssen, Lilly, Novartis, Pfizer, Roche, UCB, Viatris. Susan J. Bartlett: Past 36 months: Leadership or fiduciary role in other board, society, committee or advocacy group, paid or unpaid: American Thoracic Society Board of Directors: 2020–2022; unpaid. PROMIS Health Organization – President Elect, Board of Directors: unpaid. American College of Rheumatology Association of Rheumatology Professionals Executive Committee: 2021–2023; unpaid. Simon Stones: Past 36 months: Consulting fees: Future Science Group: Payment for document review. Leadership or fiduciary role in other board, society, committee or advocacy group, paid or unpaid: RAiISE: Director. Stock or stock options: Envision Pharma Group: Related to employment. Other financial or non-financial interests: Envision Pharma Group: Employment. Esi Morgan: Past 36 months: Grants or contracts from any entity: Pfizer, Inc: Educational Program to Optimize Delivery of Care to Families with Juvenile Idiopathic Arthritis Over Telemedicine; Investigator Initiated Grant to Seattle Children's Research Institute, role – co-Investigator. Agency for Healthcare Research and Quality: Informing personalized treatment decision with advanced Bayesian causal inference - A patient-centred evidence-based shared decision making (SDM) digital health technology; Investigator Initiated Grant to Seattle Children's Research Institute, role – PI (multi-PI grant). Payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events: American College of Rheumatology: Honorarium, Education Conference April 2023. Support for attending meetings and/or travel: American College of Rheumatology: Travel Support Education Exchange Conference April 2023. Leadership or fiduciary role in other board, society, committee or advocacy group, paid or unpaid: pediatric Rheumatology Care and Outcomes Improvement Network: Principal Investigator. Francis GUILLEMIN: Past 36 months: Grants or contracts from any entity: Novartis: Payment to my institution. Hemalatha Srinivasalu: Past 36 months: Grants or contracts from any entity: CARRA Registry Associate and NIAMS Intramural program. Janet Jull: Past 36 months: Grants or contracts from any entity: Canadian Institutes of Health Research. Jennifer L. Barton: Past 36 months: Grants or contracts from any entity: US Department of Veterans Affairs. Jasvinder A. Singh: Past 36 months: Consulting fees: Crealta/Horizon, Medisys, Fidia, PK Med, Two labs Inc., Adept Field Solutions, Clinical Care options, Clearview healthcare partners, Putnam associates, Focus forward, Navigant consulting, Spherix, MedIQ, Jupiter Life Science, UBM LLC, Trio Health, Medscape, WebMD, and Practice Point communications; and the National Institutes of Health and the American College of Rheumatology: Consultant fees paid to me for each entity. Payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events: JAS is on the speaker's bureau of Simply Speaking: Consultant fees paid to me. Support for attending meetings and/or travel: Past steering committee member of OMERACT: I previously received support from the organization to attend their meeting every 2 years. Participation on a Data Safety Monitoring Board or Advisory Board: FDA Arthritis Advisory Committee: JAS serves as a member. No financial support. Leadership or fiduciary role in other board, society, committee or advocacy group, paid or unpaid: Past steering committee member of the OMERACT, an international organization that develops measures for clinical trials and receives arms length funding from 12 pharmaceutical companies: I previously received support from the organization to attend their meeting every 2 years. Co-Chair of the Veterans Affairs Rheumatology Field Advisory Committee: No financial support. Editor and the Director of the UAB Cochrane Musculoskeletal Group Satellite center on Network Meta-analysis: No financial support. Stock or stock options: JAS owns stock options in Atai life sciences, Kintara therapeutics, Intelligent Biosolutions, Acumen pharmaceutical, TPT Global Tech, Vaxart pharmaceuticals, Atyu biopharma, Adaptimmune Therapeutics, GeoVax Labs, Pieris Pharmaceuticals, Enzolytics Inc., Seres Therapeutics, Tonix Pharmaceuticals Holding Corp., and Charlotte's Web Holdings, Inc.: I own stock options. JAS previously owned stock options in Amarin, Viking and Moderna pharmaceuticals: I owned stock options in these companies previously. Saurab Sharma: Past 36 months: Grants or contracts from any entity: I am supported by the International Association for the Study of Pain John J. Bonica Postdoctoral Fellowship. The funder does not have any influence on my research. Support for attending meetings and/or travel: My travel was supported to present a talk (unrelated to the manuscript) at the International Association for the Study of Pain (IASP) Congress in Toronto in 2022. Victor Sloan: Past 36 months: Consulting fees: Boehringer-Ingelheim: Payment to me. Stock or stock options: Stock in UCB Pharma. Willemina Campbell: Past 36 months: Payment or honoraria for lectures, presentations, speakers’ bureaus, manuscript writing or educational events: ABBVIE and Einstein Medical School. Support for attending meetings and/or travel: OMERACT and GRAPPA. Leadership or fiduciary role in other board, society, committee or advocacy group, paid or unpaid: GRAPPA PRP CHAIR-past., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Objectives: To generate candidates for contextual factors (CFs) for each CF type (i.e., Effect Modifying Contextual Factors (EM-CFs), Outcome Influencing Contextual Factors (OI-CFs), and Measurement Affecting Contextual Factors (MA-CFs)) considered important within rheumatology., Methods: We surveyed OMERACT working groups and conducted a Special Interest Group (SIG) session at the OMERACT 2023 meeting, where the results were reviewed, and additional CFs suggested., Results: The working groups suggested 44, 49, and 21 generic EM-CFs, OI-CFs, and MA-CFs, respectively. SIG participants added 49, 44, and 55 factors, respectively., Conclusion: Candidate CFs were identified, next step is a consensus-based set of endorsed (important) CFs., Competing Interests: Declaration of competing interest Amye Leong reports unpaid leadership or fiduciary roles at the Arthritis Foundation, the United States Bones and Joint Initiative and the FDA Patient Engagement Advisory Committee. Annelies Boonen reports a research grant from Abbvie and honoraria from Abbvie, Pfizer, UCB, Novartis and Galapagos for lectures or advisory boards, all to her department. Dorthe Bang Berthelsen reports PhD Scholarships from Odense University Hospital and from the Faculty of Health Sciences, University of Southern Denmark. Francis Guillemin reports grant by Novartis, paid to his institution. Irene van der Horst-Bruinsma reports travel support for EULAR 2023 by Pfizer and unpaid membership in the ASAS advisory board. Maria A. Lopez-Olivo reports grants or contracts from the National Cancer Institute, the Rheumatology Research Foundation and the Duncan Family Institute for Cancer Prevention and Risk Assessment, and consulting fees from the American Cancer Society. Niti Goel reports that she is an owner of stock in Abcuro and UCB and that she is a former employee of TrialSpark, Inc. Peter Tugwell reports consulting fees from the Reformulary Group, being independent Committee Member for clinical trial Data Safety Monitoring Boards for UCB Biopharma GmbH & SPRL, Parexel International and PRA Health Sciences and being chair of the Management Group of OMERACT, a registered non-profit independent medical research organization. OMERACT receives arms-length funding from eleven companies (Abbvie, Astra Zenaca, Aurinia, BMS, Centrexion, GSK, Horizon Pharma Inc, Janssen, Novartis, Pfizer, Sparrow). Rieke Alten reports personal and institutional payments from BMS, Galapagos, Janssen, Lilly, Novartis, Pfizer and UCB as wells as institutional payments from Abbvie and Amgen, support for attending meetings from Celltrion, Lilly and UCB, and membership of an advisory board for Pfizer. Saurab Sharma was supported by the International Association for the Study of Pain John J. Bonica Postdoctoral Fellowship (2021-2023) and travel support to the International Association for the Study of Pain (IASP) Congress in Toronto (2022) both unrelated to the current work. Victor S. Sloan reports consulting fees from Boehringer-Ingelheim, stock in UCB Pharma and as an employee of the Peace Corps states: “This is my personal work, and does not reflect the opinion of the Peace Corps or the United States Government.”. The other authors have no conflict of interest relevant to the content of this study., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Abstract: Nonradiographic axial spondyloarthritis (nr-axSpA) represents a distinct phenotype within the spectrum of axial spondyloarthritis (axSpA), which is characterized by a range of clinical manifestations. Despite a high disease burden that is comparable to ankylosing spondylitis (also known as radiographic axSpA), there is an unmet need to recognize and effectively manage patients with active nr-axSpA.A targeted literature search was conducted in OVID (MEDLINE and Embase databases) to identify articles on nr-axSpA, including its definition, demographics, epidemiology, burden, diagnosis, clinical presentation, and treatment guidelines.The lack of adequate epidemiological data and incomplete understanding of nr-axSpA among rheumatologists and nonrheumatologists contributes to delayed referrals and diagnosis. This delay results in a substantial burden on patients, physically and psychologically, and the healthcare system. Targeted therapies, such as biologics, including inhibitors of tumor necrosis factor or interleukin-17A, have been approved and utilized for the management of nr-axSpA, and other novel therapeutics with different mechanisms of action are in development. Raising awareness among US internists regarding the prevalence of nr-axSpA, disease burden, clinical presentation, diagnostic tools, and available treatments is important for improved disease management.Future clinical investigations focusing on the development of markers that aid early diagnosis and predict treatment response may also improve the management of nr-axSpA. This review provides an overview of nr-axSpA with the aim of raising awareness of the disease among US internists, with an overarching goal to contribute toward the improved recognition and timely referral of these patients to rheumatologists for diagnosis and management., (Copyright © 2022 the Author(s). Published by Wolters Kluwer Health, Inc.)

Introduction: Current epidemiologic literature of rheumatologic immune-related adverse events (rh-irAEs) consists of clinical trials, case reports, or smaller, single-center series. We evaluate the occurrence of rh-irAEs during immune checkpoint inhibitor (ICI) therapy from US commercial claims data., Methods: Patients newly initiating ICI therapy in commercial claims data were eligible for inclusion. Rh-irAEs were defined using ≥ 1 International Classification of Diseases (ICD)-9 or ICD-10-Clinical Modification (CM) claims for selected events, ranging from joint pain and myalgia to ankylosing spondylitis and psoriasis. The percentage of patients experiencing rh-irAEs after ICI initiation was determined., Results: A total of 5722 patients initiating an ICI between January 1, 2012, and June 30, 2018, were included; 201 patients (3.5%) had a history of rheumatic disease. Among the 5521 patients without a history of rheumatic disease, 29.6% experienced ≥ 1 rh-irAE in follow-up, decreasing to 22.6% when assessing events for which there was no diagnostic history. Limiting to claims for rh-irAE with a rheumatologist provider, the proportion of patients experiencing an event decreased to 0.9%. Among patients with a history of rheumatic disease, 71.6% experienced ≥ 1 rh-irAE. Limiting to events for which the patient did not have a history during baseline, 35.3% experienced an event., Conclusions: Occurrence of rh-irAEs during ICI use is higher in patients with pre-existing rheumatic disease compared to those with no pre-existing rheumatic disease. However, the most common events were not definitive rheumatic diseases but rather symptoms, such as pain in joints. Occurrence of events associated with a rheumatologist provider was substantially lower, suggesting that either patients are not referred to a rheumatologist or referral does not result in confirmation of the diagnosis by the rheumatologist., (© 2021. The Author(s).)

Objectives: Imaging is one of the most rapidly evolving fields in medicine. Unfortunately, many imaging technologies have been applied as measurement instruments without rigorous evaluation of the evidence supporting their truth, discriminatory capability and feasibility for that context of use. The Outcome Measures in Rheumatology (OMERACT) Filter 2.1 Instrument Selection Algorithm (OFISA) is used to evaluate such evidence for use of an instrument in a research setting. The objectives of this work are to: [1] define and describe the key conceptual aspects that are essential for the evaluation of imaging as an outcome measurement instrument and [2] describe how these aspects can be assessed through OFISA., Methods: Experts in imaging and/or methodology met to formalize concepts and define key steps. These concepts were discussed with a team of patient research partners with interest in imaging to refine technical and methodological aspects into comprehensible information. A workshop was held at OMERACT2020 and feedback was incorporated into existing OMERACT process for domain and instrument selection., Results: Three key lessons were identified: (1) a clear definition of the domain we want to measure is a necessary prerequisite to the selection of a good instrument, (2) the sources of variability that can directly influence the instrument should be clearly identified, (3) incorporating these first two lessons into OFISA improves the quality of every instrument selection process., Conclusions: The incorporation of these lessons in the updated OMERACT Filter (now 2.2) will improve the quality of the selection process for all types of outcome measurement instruments., Competing Interests: Declaration of Competing Interest Dorcas Beaton, Paul Bird, Maarten Boers, Sam Michel Cembalo, Philip Conaghan, Maria Antonietta D'Agostino, Maarten de Wit, Alison Hoens, Catherine Hofstetter, Lara Maxwell, Win Min Oo, Marion van Rossum, Teodora Serban, Lene Terslev, Codruta Zabalan report they have nothing to disclose. Andrea Doria reports: Advisory Board(s) International Prophylaxis Study Group (not for profit), OMERACT SIG in MRI in JIA (not for profit), Research Support Baxalta-Shire (Research Grant), Novo Nordisk (Research Grant), Terry Fox Foundation (Research Grant), PSI Foundation (Research Grant), Society of Pediatric Radiology (Research Grant), Garron Family Cancer Centre (Research Grant). Robin Christensen reports: The Parker Institute is grateful for the financial support received from public and private foundations, companies and private individuals over the years. The Parker Institute is supported by a core grant from the Oak Foundation; The Oak Foundation is a group of philanthropic organizations that, since its establishment in 1983, has given grants to not-for-profit organizations around the world. Prof. Christensen is a founding member of the Technical Advisory Group of OMERACT, an organization that develops outcome measures in rheumatology and receives arms-length funding from 12 companies. Walter P. Maksymowych is Chief Medical Officer of CARE Arthritis, a company that develops and validates imaging-based scoring systems for application in clinical trials and basic and clinical research of arthritis disorders. Victor Sloan reports stock for service as member of Board of Directors of Oncopath Genomics LLC outside the submitted work and as CEO of Sheng Consulting LLC I provided clinical research consulting services to several pharmaceutical companies involved in developing new therapies for autoimmune disease. Mikkel Østergaard reports grants, personal fees and non-financial support from AbbVie, grants, personal fees and non-financial support from BMS, personal fees from Boehringer-Ingelheim, personal fees from Eli Lilly, personal fees and non-financial support from Janssen, grants, personal fees and non-financial support from Merck, personal fees and non-financial support from Pfizer, personal fees and non-financial support from Roche, grants, personal fees and non-financial support from UCB, grants and personal fees from Celgene, personal fees from Sanofi, personal fees from Regeneron, grants, personal fees and non-financial support from Novartis, personal fees from Gilead, outside the submitted work., (Copyright © 2021. Published by Elsevier Inc.)

Objective: To gain consensus on the Outcome Measures in Rheumatology (OMERACT) core domain set for rheumatology trials of shared decision making (SDM) interventions., Methods: The process followed the OMERACT Filter 2.1 methodology, and used consensus-building methods, with patients involved since the inception. After developing the draft core domain set in previous research, we conducted five steps: (i) improving the draft core domain set; (ii) developing and disseminating white-board videos to promote its understanding; (iii) conducting an electronic survey to gather feedback on the draft core domain set; (iv) finalizing the core domain set and developing summaries, a plenary session video and discussion boards to promote its understanding; and (v) conducting virtual workshops with voting to endorse the core domain set., Results: A total of 167 participants from 28 countries answered the survey (62% were patients/caregivers). Most participants rated domains as relevant (81%-95%) and clear (82%-93%). A total of 149 participants (n = 48 patients/caregivers, 101 clinicians/researchers) participated in virtual workshops and voted on the proposed core domain set which received endorsement by 95%. Endorsed domains are: 1- Knowledge of options, their potential benefits and harms; 2- Chosen option aligned with each patient's values and preferences; 3- Confidence in the chosen option; 4- Satisfaction with the decision-making process; 5- Adherence to the chosen option and 6- Potential negative consequences of the SDM intervention., Conclusion: We achieved consensus among an international group of stakeholders on the OMERACT core domain set for rheumatology trials of SDM interventions. Future research will develop the Core Outcome Measurement Set., Clinical Significance: Prior to this study, there had been no consensus on the OMERACT core domain set for SDM interventions. The current study shows that the OMERACT core domain set achieved a high level of endorsement by key stakeholders, including patients/caregivers, clinicians and researchers., Competing Interests: Declaration of Competing Interest Karine Toupin-April, Simon Décary, Maarten de Wit, Alexa Meara, Jennifer L. Barton, Liana Fraenkel, Linda C. Li, Peter Brooks, Beverley Shea, Dawn Stacey, France Légaré, Anne Lyddiatt, Cathie Hofstetter, Laurie Proulx, Marieke Voshaar, Maria E. Suarez-Almazor, Tanya Meade, Janet Elizabeth Jull, Willemina Campbell, Rieke Alten, Esi M. Morgan, Ayano Kelly, Jessica Kaufman, Lara J. Maxwell, Francis Guillemin, Dorcas Beaton, Yasser El-Miedany, Shikha Mittoo, Tiffany Westrich Robertson, Susan J. Bartlett, Melissa Mannion, Samah Ismail Nasef, Savia de Souza, Anne Boel, Adewale Adebajo, Laurent Arnaud, Tiffany Gill, Ellen Moholt, Jennifer Burt, Aruni Jayatilleke, Ihsane Hmamouchi, David Carrott, Kate Mather, Ajesh Maharaj, Saurab Sharma, Francesco Caso, Christopher Fong, Allyson Jones, Regina Greer-Smith, Akpabio Akpabio, Valerie Umaefulam, Sara Monti, Charmaine Melburn, Kirsten Schultz, Simon Stones, Sonam Kiwalkar, Hemalatha Srinivasalu, Deb Constien, Lauren K. King and Peter Tugwell have nothing to disclose. Robin Christensen reports other from Lecture: Research Methods (Pfizer, DK; 2017), other from Lecture: GRADE Lecture (Celgene, DK; 2017), other from Ad Board Lecture: CAM (Orkla Health, DK; 2017), other from Project Grant: "GreenWhistle" (Mundipharma, 2019), other from Lecture: Diet in RMD (Novartis, DK; 2019), other from Consultancy Report: Network MA's (Biogen, DK; 2017), other from Ad Board Lecture: GRADE (Lilly, DK; 2017), other from Consultancy Report: GRADE (Celgene, 2018), other from Lecture: Network MA's (LEO; 2020), outside the submitted work; and Musculoskeletal Statistics Unit, The Parker Institute is grateful for the financial support received from public and private foundations, companies and private individuals over the years. The Parker Institute is supported by a core grant from the Oak Foundation; The Oak Foundation is a group of philanthropic organizations that, since its establishment in 1983, has given grants to not-for-profit organizations around the world. Annelies Boonen reports grants from Abbvie, grants from Celgene, other from UCB, other from Galapagos, other from Eli Lilly, outside the submitted work. Lyn March reports personal fees from Pfizer Australia, personal fees from Abbvie Australia, grants from Janssen Australia, outside the submitted work; Dr March is a member of OMERACT executive that receives arms-length funding from 9 companies. Willemina Campbell received OMERACT funded travel to a conference to attend meetings in regard to this paper. Sophie Hill is the Coordinating Editor of the Cochrane Consumers and Communication Group which publishes reviews of the evidence on shared decision making. Jasvinder Singh reports personal fees from Crealta/Horizon, Medisys, Fidia, UBM LLC, Trio health, Medscape, WebMD, Adept Field Solutions, Clinical Care options, Clearview healthcare partners, Putnam associates, Focus forward, Navigant consulting, Spherix, Practice Point communications, the National Institutes of Health and the American College of Rheumatology, personal fees from Simply Speaking, other from Vaxart pharmaceuticals and Charlotte's Web Holdings (current); Amarin, Viking, and Moderna (previously owned), non-financial support from FDA Arthritis Advisory Committee, non-financial support from Steering committee of OMERACT, an international organization that develops measures for clinical trials and receives arms’ length funding from 12 pharmaceutical companies, non-financial support from Veterans Affairs Rheumatology Field Advisory Committee, non-financial support from Editor and the Director of the UAB Cochrane Musculoskeletal Group Satellite Center on Network Meta-analysis, outside the submitted work. Francisco J. Blanco reports grants from Abbvie, grants and personal fees from Pfizer, grants from UCB, grants from Bristol-Mayers Squibb, grants from Roche, grants from Servier, grants from Bioiberica, grants from Sanofie, grants from Grunenthal, grants from GlaxoSmithKline, grants from Lilly, grants from Janssen, grants from Regeneron, grants from Amgen, grants from TRB Chemedica, outside the submitted work. Anthony P. Fernandez reports personal fees and other from AbbVie, grants, personal fees and other from Novartis, grants, personal fees and other from Mallinkrodt, other from Corbus, other from Pfizer, outside the submitted work. Sarah Mackie reports other from Roche Chugai, non-financial support from Roche, other from Sanofi, outside the submitted work; and Patron of the patient charity PMRGCAuk. Elena Nikiphorou reports personal fees and other from AbbVie, personal fees and other from Eli-Lilly, personal fees and other from Gilead, personal fees and other from Celltrion, personal fees and other from Pfizer, other from Sanofi, outside the submitted work. Victor S. Sloan reports having served as paid consultant to various pharmaceuticalcompanies and healthcare consultancies providing advice on clinicalresearch and advisory committee preparation outside the scope of thesubmitted work. Shareholder in UCB Pharma. Vibeke Strand reports consulting fees from AbbVie, Amgen, Arena, AstraZeneca, BMS, Boehringer Ingelheim, Celltrion, CORRONA, Crescendo/Myriad, Equillium, Genentech/Roche, GSK, Horizon, Inmedix, Janssen, Eli Lilly, Novartis, Pfizer, Regeneron Pharmaceuticals Inc., Samsung, Sandoz, Sanofi, TwoXAR and UCB, outside the submitted work., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Introduction: The Outcome Measures in Rheumatology Clinical Trials (OMERACT) Rheumatology Common Toxicity Criteria (RCTC) version 2.0 was published in 2007 by the OMERACT Drug Safety Working Group, building on limited experience with RCTC version 1.0, to facilitate standardization of assessment (grading) and reporting of adverse events (AEs) commonly seen in rheumatic disease clinical trials (Woodworth et al. in J Rheumatol 34:1401-1414, 2007)., Objectives: The objectives of this study were to (1) report the real-world performance of RCTC 2.0; (2) report immediately correctable errors in RCTC 2.0, and provide a revised RCTC 2.1; and (3) begin to identify the need for a comprehensive revision of RCTC 2.0., Methods: Safety data outputs for several large rheumatic/autoimmune disease clinical trials in which RCTC 2.0 was used were evaluated for accuracy of reporting and the ability to assess differences among treatments. We examined RCTC 2.0 tables for errors, as well as for omission of terms for AEs that commonly occur in more recent rheumatology clinical trials. We also considered recommendations from recent US Food and Drug Administration (FDA) and international initiatives such CDISC (Clinical Data Interchange Standards Consortium) to improve the consistency of safety data collection and interpretability of safety data analyses., Results: RCTC 2.0 enabled comparisons of safety data across treatment groups, including grading. However, we discovered inaccuracies in laboratory results grading and omission of AE terms now recognized to occur in rheumatic disease clinical trials., Conclusion: The RCTC 2.0 performed as intended, although some inaccuracies and omissions were found. We provide a corrected version, RCTC 2.1, and also recommend further revision of the RCTC within OMERACT guidances to include AEs that have been reported in rheumatology clinical trials since RCTC 2.0 was published. Ideally, a revised RCTC 3.0 would not only facilitate standardized assessment and reporting of AEs, but would also expand and encourage accurate comparison of the safety profiles of treatments for rheumatic/autoimmune diseases.

Objective: To assess the prevalence of chronic opioid use in patients with ankylosing spondylitis (AS), and to compare the characteristics of patients with and without chronic opioid use., Methods: This was a retrospective cohort study of patients with AS identified in the Truven Health MarketScan Research database between January 1, 2012, and March 31, 2017. Commercial and Medicaid claims data were examined using both specific (720.0 and M45.x) and broader (720.x and M45.x) International Classification of Diseases (ICD) coding definitions. Patients were aged ≥ 18 years on the date of first qualifying ICD code occurrence (the index date). Demographics and clinical characteristics were assessed in the 12-month period preceding the index date. The 12-month followup period was used to assess prevalence and characteristics of chronic opioid use., Results: Chronic opioid use was common among patients with commercial claims (23.5% of ICD 720.0 patients; 27.3% of ICD 720.x patients), and especially those with Medicaid claims (57.1% and 76.7%, respectively). The proportion of patients with claims for anti-tumor necrosis factor therapies during followup was often low, and for Medicaid patients was lower among those with chronic opioid use (29.6% of ICD 720.0 patients; 2.3% of ICD 720.x patients) than those without (47.1% and 7.1%, respectively). Among chronic opioid users in all cohorts, the cumulative supply of opioids was typically high (≥ 270 days in the followup period); most opioids prescribed were Schedule II., Conclusion: Patients with AS receive opioids with disturbing frequency. The infrequent prescription of recommended therapies to these patients reflects a need to optimize treatment further through education of patients and healthcare professionals alike.

Objective: The Outcome Measures in Rheumatology (OMERACT) Safety Working Group objective was to identify harm domains from existing outcome measurements in rheumatology., Methods: Systematically searching the MEDLINE database on January 24, 2017, we identified full-text articles that could be used for harm outcomes in rheumatology. Domains/items from the identified instruments were described and the content synthesized to provide a preliminary framework for harm outcomes., Results: From 435 possible references, 24 were read in full text and 9 were included: 7 measurement instruments were identified. Investigation of domains/items revealed considerable heterogeneity in the grouping and approach., Conclusion: The ideal way to assess harm aspects from the patients' perspective has not yet been ascertained.

Objective: To assess the expanded/refined first-time participant training program., Methods: We conducted a refined new participant program at OMERACT 2018 on days 1-4, in which first-time participants provided feedback with online surveys and a nominal group on Day 4., Results: Twenty first-time participants attended the introductory session and 8-12 attended followup sessions. A high proportion valued the newbie session (100%), rating it overall (91%), content-wise (62%), for presentation quality (82%), and value for the money (82%) as outstanding or good. The nominal group technique identified opportunities for further improvement of breakouts/voting., Conclusion: The expanded new participant training program is valued by attendees.

Hydrocodone/chlorpheniramine is a prescription opioid licensed in the USA for the relief of cough and upper respiratory symptoms associated with allergy or cold in adults, previously contraindicated in children aged < 6 years. We present findings from a modern benefit risk review of hydrocodone/chlorpheniramine use as an antitussive agent in patients aged 6 to < 18 years. A cumulative search of the manufacturer's pharmacovigilance database covering 1 January 1900-7 August 2017 identified all individual case safety reports (ICSRs) associated with product family name "hydrocodone/chlorpheniramine." The search was inclusive of all MedDRA system organ classes, stratified by age (< 18 years). A comprehensive review of the scientific literature was conducted on safety and efficacy of opioids for pediatric treatment of cough. Three hundred and ninety-one ICSRs associated with hydrocodone/chlorpheniramine were identified; 35/391 ICSRs were in patients < 18 years of age; 18 were considered serious. Four fatalities were reported in patients 6 to < 18 years; two fatalities involved co-suspect medication azithromycin and two were poorly documented. Our literature search identified no robust efficacy data for hydrocodone/chlorpheniramine in the relief of cough and upper respiratory symptoms associated with allergy or cold in patients aged 6 to < 18 years. As we found no evidence of hydrocodone/chlorpheniramine efficacy in the pediatric population, we conclude that the benefit risk profile is unfavorable. This evidence contributed to the US Food and Drug Administration's (FDA's) recent decision that hydrocodone-containing cough and cold medications should no longer be indicated for treatment of cough in patients < 18 years, highlighting the value of proactive re-evaluation of the benefit risk profile of older established drugs. Plain Language Summary People often use medicines containing opioids to treat cough symptoms. The US Food and Drug Administration (FDA) recently decided that cough medicines containing opioids should not be used by children under 18 years old. Part of this decision was a review of the benefits and risks of using cough medicines that contain the opioid hydrocodone in children.Why was this review carried out? Most cough medicines that doctors can prescribe were approved several decades ago. Since then, rules for the approval of medicines have become stricter. In this review, researchers looked at the safety of hydrocodone, and how well this opioid relieves cough symptoms in children. Up-to-date information and modern research methods were used.The two key pieces of evidence found were: We could not locate any clinical trials providing robust evidence for the use of hydrocodone for cough relief in children under 18 years of age. (Outside the scope of this review, a number of clinical trials of hydrocodone-containing cough medicines in adults aged 18 years and over have shown the medicine to be effective in these patients.) Cough medicines containing opioids can cause harmful side effects in children such as breathing problems. In the research reported here, ten children died after taking a hydrocodone-containing cough medicine. Nine of these deaths were due to overdose. This evidence was used to draw the following conclusions: In children under 18 years of age, the risks of using hydrocodone for cough relief are greater than any benefits. Older medicines should be reviewed regularly to look at their safety and how well they are working using up-to-date evidence.

The 'Ecohealth and Watersheds in Northern BC'' project, situated in a resource rich, settler colonial context, generated three digital stories at the request of the project's Steering Committee members that sought to connect health, environment, and community. Three Steering Committee members championed these stories from their distinct watersheds, resulting in emergent counter-narratives that respond directly to their social-ecological contexts. Nested in literature on blue and green spaces, we present and examine the process of storytelling as emergent counter-narrative and how these narratives challenge us to think of blue and green spaces in interconnected and nuanced ways., (Copyright © 2018. Published by Elsevier Ltd.)

Objective: To describe the experience of the first-time participant (newbie) training program at the Outcome Measures in Rheumatology (OMERACT) 2016 meeting., Methods: We conducted new participant sessions at OMERACT 2016, including a 2-h introductory session on Day 1 followed by 1-h evening followup sessions on days 1-4. Pre- and post-meeting surveys assessed participants' levels of comfort with the principles of the OMERACT Filter 2.0 (the essential tools for OMERACT methodology) and the different types of OMERACT sessions, and whether participants felt welcome. In addition, on the final day, a nominal group technique was used to elicit problematic components of the meeting and to develop solutions to those problems., Results: Of the 43 new attendees, 38 participated in the introductory session and 14-18 attended the followup sessions. Comparing Day 1 (preintroductory session) to days 1-3 (post), a similar proportion understood different types of sessions extremely well [45% (pre) versus 47%, 44%, and 36% (post), respectively], and a higher proportion understood principles of the OMERACT filter extremely well [22% (pre) versus 55%, 44%, and 40% (post), respectively]. Most reported feeling welcome (86.7%) and felt they contributed to breakout sessions (93.3%) on the evening of Day 1; results were sustained on days 2-3. The most commonly reported "best" experience included the OMERACT culture and the most common reported experience needing improvement included facilitation issues during breakouts., Conclusion: The first-time participants came to OMERACT 2016 with a high baseline level of understanding. They rapidly attained a high comfort level with participation and provided concrete and innovative solutions to the most commonly reported experiences needing improvement.

Several noncardiac drugs have been linked to cardiac safety concerns, highlighting the importance of post-marketing surveillance and continued evaluation of the benefit-risk of long-established drugs. Here, we examine the risk of QT prolongation and/or torsade de pointes (TdP) associated with the use of hydroxyzine, a first generation sedating antihistamine. We have used a combined methodological approach to re-evaluate the cardiac safety profile of hydroxyzine, including: (1) a full review of the sponsor pharmacovigilance safety database to examine real-world data on the risk of QT prolongation and/or TdP associated with hydroxyzine use and (2) nonclinical electrophysiological studies to examine concentration-dependent effects of hydroxyzine on a range of human cardiac ion channels. Based on a review of pharmacovigilance data between 14th December 1955 and 1st August 2016, we identified 59 reports of QT prolongation and/or TdP potentially linked to hydroxyzine use. Aside from intentional overdose, all cases involved underlying medical conditions or concomitant medications that constituted at least 1 additional risk factor for such events. The combination of cardiovascular disorders plus concomitant treatment of drugs known to induce arrhythmia was identified as the greatest combined risk factor. Parallel patch-clamp studies demonstrated hydroxyzine concentration-dependent inhibition of several human cardiac ion channels, including the ether-a-go-go-related gene (hERG) potassium ion channels. Results from this analysis support the listing of hydroxyzine as a drug with "conditional risk of TdP" and are in line with recommendations to limit hydroxyzine use in patients with known underlying risk factors for QT prolongation and/or TdP.

Objective: To describe the experience of a first-time participant ("newbie") training program at the Outcome Measures in Rheumatology 12 meeting in 2014., Methods: We conducted newbie sessions at OMERACT 12, including a 2-hour introductory session on Day 1, followed by 1-h evening followup sessions on days 1-4 of OMERACT 12. Pre- and postmeeting surveys assessed participants' level of comfort with the principles of the OMERACT Filters 1.0 (truth, discrimination, feasibility), and Filter 2.0 (the essential tools for OMERACT methodology), the different types of OMERACT sessions, and whether participants felt welcome., Results: In all, 25 new attendees participated in the introductory session and 10-16 attended followup sessions. Fewer participants reported being somewhat or extremely uncomfortable with the meeting, comparing Day 1 (preintroductory session) to days 1-4 (post): (1) with different OMERACT sessions: 56% (pre) versus 6%, 0%, 8%, and 6% (post days 1-4, respectively); and (2) with principles of the OMERACT filter, 64% (pre) versus 7%, 0%, 8%, and 0% (post), respectively. Most reported feeling welcome (100%) and that they were able to contribute substantively to breakout sessions (87%) on Day 1 evening; results were sustained on days 2-4., Conclusion: First-time participant training sessions increased the comfort level of the participants with the OMERACT meeting structure and filter, and increased the ability of the new attendees to feel they could contribute to the OMERACT process.

Ethical tensions exist regarding the value and practice of acknowledging Indigenous contributions in community-based participatory research (CBPR). Semistructured phone interviews with researchers documented their perspectives on authorship in the scholarly dissemination of their community-based participatory Indigenous research. Thematic analysis resulted in four key ideas: (1) current practices regarding methods of acknowledging community contributions; (2) requirements for shared authorship with individual versus collective/community partners; (3) benefits to sharing authorship with collective/community partners; and (4) risks to sharing authorship with collective/community partners. Findings suggest an emerging but inconsistent practice.

Phosphodiesterase 4 (PDE4) is a key enzyme in the degradation of cyclic adenosine monophosphate and is centrally involved in the cytokine production of inflammatory cells, angiogenesis, and the functional properties of other cell types such as keratinocytes. In this review article, apremilast, a novel small molecule inhibitor of PDE4, is introduced. Apremilast has profound anti-inflammatory properties in animal models of inflammatory disease, as well as human chronic inflammatory diseases such as psoriasis and psoriatic arthritis. Apremilast blocks the synthesis of several pro-inflammatory cytokines and chemokines, such as tumor necrosis factor alpha, interleukin 23, CXCL9, and CXCL10 in multiple cell types. In contrast to the biologics, which neutralize pro-inflammatory mediators at the protein level, apremilast modulates production of these mediators at the level of mRNA expression. Apremilast also interferes with the production of leukotriene B4, inducible nitric oxide synthase, and matrix metalloproteinase and reduces complex inflammatory processes, such as dendritic cell infiltration, epidermal skin thickening, and joint destruction. As this novel PDE4 inhibitor interferes with several key processes of inflammation, it may emerge as a promising new drug for the treatment of chronic inflammatory diseases such as those of the skin and the joints.

Objective: Bisphosphonates inhibit osteoclast activity, which is central to the development of bone damage in rheumatoid arthritis (RA). The aim of this study was to assess whether treatment with zoledronic acid, compared with placebo, could achieve a > or = 50% reduction in the development of new erosions on magnetic resonance imaging (MRI) in patients with early RA., Methods: In this proof-of-concept study, 39 patients with early RA and clinical synovitis of the hand/wrist were randomized to receive infusions with either zoledronic acid (5 mg) or placebo, administered at baseline and week 13. Patients in both groups received methotrexate (MTX) at a dosage of 7.5-20 mg/week. MRI and plain radiography were performed at baseline and week 26., Results: At week 26, the mean +/- SD change in MRI hand and wrist erosions was 61% lower in the zoledronic acid group compared with the placebo group (0.9 +/- 1.63 versus 2.3 +/- 3.09; P = 0.176). The mean +/- SD increase in the number of hand and wrist bones with erosions was 0.3 +/- 0.75 for zoledronic acid compared with 1.4 +/- 1.77 for placebo (P = 0.029). The proportion of patients in whom new MRI-visualized bone edema developed was smaller in the zoledronic acid group compared with the placebo group (33% versus 58%; P = 0.121). The zoledronic acid group had a mean change in the number of radiographic erosions of 0.1 compared with 0.5 for the placebo group (P = 0.677). The safety profile of zoledronic acid was similar to that of placebo., Conclusion: The results of this study suggest a structural benefit associated with zoledronic acid therapy in patients with RA, as demonstrated by consistent results in structural end points in favor of zoledronic acid plus MTX compared with MTX alone.

The objective of this study was to evaluate the efficacy, safety and tolerability of lumiracoxib compared with placebo and celecoxib in patients with osteoarthritis (OA). Following a 3- to 7-day washout period for previous non-steroidal anti-inflammatory drugs, 1,600 patients aged >or=18 years with primary knee OA were randomized to receive lumiracoxib 200 or 400 mg once daily (o.d.), celecoxib 200 mg o.d. or placebo for 13 weeks. Primary efficacy variables were OA pain intensity in the target knee, patient's global assessment of disease activity and the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain subscale and total scores at week 13. Secondary variables included OA pain intensity in the target knee and physician's and patient's global assessments of disease activity by visit. Exploratory analysis of responder rates using the Outcomes Measures in Rheumatology Clinical Trials-Osteoarthritis Research Society International (OMERACT-OARSI) criteria was performed. Safety and tolerability were assessed. Lumiracoxib was superior to placebo in all primary and secondary variables and was generally similar to celecoxib. There were no statistically significant differences between the two doses of lumiracoxib. All active treatments were significantly more effective than placebo at weeks 2 and 13 in terms of response to treatment assessed using OMERACT-OARSI criteria. The incidence of adverse events was similar across the groups. Lumiracoxib 200 mg o.d. is a well-tolerated and effective treatment option for OA of the knee, providing pain relief and improved functional status with efficacy superior to placebo and similar to celecoxib. Lumiracoxib demonstrated a tolerability profile similar to placebo and celecoxib.

Objective: To determine the efficacy and safety of lumiracoxib for knee osteoarthritis (OA)., Methods: This was a 13-week, multicentre, randomized, double-blind, double-dummy, placebo-controlled study. Males or females aged >/= 18 years with primary knee OA received lumiracoxib 100 mg od, lumiracoxib 100 mg od with a loading dose of 200 mg od for the first two weeks, celecoxib 200 mg od, or placebo., Main Outcome Measures: Co-primary variables, assessed at week 13, were OA pain intensity in the target knee, patient's global assessment of disease activity and the WOMAC total score. Other variables included OMERACT-OARSI responder rates and WOMAC subscale scores. Safety and tolerability were evaluated., Results: All active treatments were superior to placebo for all co-primary variables. No significant differences were observed between any active treatments. Mean reductions from baseline to week 13 for lumiracoxib 100mg od, 100mg od with loading dose, celecoxib and placebo, respectively, were: OA pain intensity in the target knee: 26.8, 26.2, 26.6 and 21.4mm (all p < 0.01 vs. placebo); patient's global assessment of disease activity: 25.1, 21.9, 22.9 and 18.9 mm (all p < 0.05 vs. placebo); WOMAC total score: 15.2, 14.8, 14.7 and 11.3 (all p < 0.01 vs. placebo). Lumiracoxib was superior to placebo and similar to celecoxib for OMERACT-OARSI response and WOMAC subscale scores. Lumiracoxib was well tolerated. The incidence of adverse events was similar across groups., Conclusions: Lumiracoxib 100 mg od provided effective relief from the pain of knee OA, with efficacy similar to celecoxib 200 mg od, and was well tolerated.

Objectives: Overview of three dose-response studies demonstrating the efficacy of lumiracoxib, a novel COX-2 selective inhibitor, for chronic pain associated with osteoarthritis (0A), or rheumatoid arthritis (RA) and acute pain following dental extraction., Methods: OA and RA: 4-week, randomized, placebo- and active-controlled studies of similar design. Patients (OA, n = 583; RA, n = 571) received lumiracoxib 50 mg, 100 mg or 200 mg twice daily (bid), lumiracoxib 400 mg once daily (od), diclofenac 75 mg bid or placebo. Dental: 12-h, single-center, randomized, placebo- and active-controlled study. Patients (n = 202) received single oral doses of lumiracoxib 100 mg or 400 mg, ibuprofen 400 mg or placebo., Main Outcome Measures: OA: pain intensity (PI) in the target joint (visual analogue scale [VAS]) and WOMAC score at Week 4; RA: overall PI (VAS) and ACR20 response at Week 4; Dental: difference (PID, categorical and VAS) score over 12h post dose, time to onset of analgesia., Results: Throughout the OA study, all lumiracoxib doses provided superior reductions in PI versus placebo and at Week 4, all lumiracoxib doses provided efficacy similar to each other and to diclofenac. In the RA study, lumiracoxib 100 mg bid, 200 mg bid and 400mg od were significantly better than placebo in PI at Weeks 1 and 2 (all p < 0.05) but demonstrated borderline significance at Week 4 (lumiracoxib 400 mg od, p = 0.06). In pain following dental surgery, PID scores for both lumiracoxib doses were superior to placebo from 1.5 h onwards and always comparable, or superior, to ibuprofen. Lumiracoxib 400 mg had the fastest onset of analgesia, measured as median time to confirmed first perceptible pain relief using the two-stopwatch method (37.4 min, superiority versus placebo, p < 0.001). Lumiracoxib was well tolerated in all studies., Conclusions: These studies provide initial evidence that lumiracoxib is an effective, well-tolerated agent for the treatment of chronic and acute pain.

A randomised, double-blind study was performed to assess the efficacy and tolerability of lumiracoxib in patients with rheumatoid arthritis (RA). Patients received lumiracoxib 200mg once daily (o.d.) (n= 280), lumiracoxib 400mg o.d. (n= 281), naproxen 500 mg twice daily (n= 279) or placebo (n= 284) for 26 weeks. The primary efficacy variable was response to treatment according to ACR20 criteria (adjusted for prohibited concomitant or excessive rescue medication use and discontinuations due to unsatisfactory therapeutic response) at week 13. Safety and tolerability was also assessed. Significantly more patients receiving lumiracoxib than placebo were responders according to ACR20 criteria at week 13 (41.1 and 42.7% for lumiracoxib 200 and 400 mg o.d., respectively; 32.4% for placebo; both p < 0.05). The proportion responding to naproxen (39.1%) was not significantly different from placebo. Prespecified gastrointestinal adverse events were more frequent with naproxen than with either lumiracoxib dose or placebo. Lumiracoxib is therefore an effective and well-tolerated therapy for RA.

Human leukocyte antigen (HLA)-DM is an unconventional major histocompatibility complex (MHC) class II heterodimer that is important for B-cell-mediated antigen processing and presentation to MHC class II-restricted T cells. HLA-DM is encoded by two genes, DMA and DMB, which map to the MHC class II region, and shares some homology with MHC class I and class II proteins. Here we define the biochemical role of HLA-DM. Recombinant soluble HLA-DM heterodimers have been purified from culture supernatants of insect cell transformants. At pH 5.0, they induce the dissociation of a subset of peptides bound to HLA-DR, including a nested set of class-II-associated invariant chain peptides (CLIP). This process liberates HLA-DR and leads to the enhanced binding of exogenous peptides.