Objective To provide guidance to rheumatology providers on the use of coronavirus disease 2019 (COVID‐19) vaccines for patients with rheumatic and musculoskeletal diseases (RMDs). Methods A task force was assembled that included 9 rheumatologists/immunologists, 2 infectious disease specialists, and 2 public health physicians. After agreeing on scoping questions, an evidence report was created that summarized the published literature and publicly available data regarding COVID‐19 vaccine efficacy and safety, as well as literature for other vaccines in RMD patients. Task force members rated their agreement with draft consensus statements on a 9‐point numerical scoring system, using a modified Delphi process and the RAND/University of California Los Angeles Appropriateness Method, with refinement and iteration over 2 sessions. Consensus was determined based on the distribution of ratings. Results Despite a paucity of direct evidence, 74 draft guidance statements were developed by the task force and agreed upon with consensus to provide guidance for use of the COVID‐19 vaccines in RMD patients and to offer recommendations regarding the use and timing of immunomodulatory therapies around the time of vaccination. Conclusion These guidance statements, made in the context of limited clinical data, are intended to provide direction to rheumatology health care providers on how to best use COVID‐19 vaccines and to facilitate implementation of vaccination strategies for RMD patients.

Background-Well characterized genes affecting warfarin metabolism (CYP2C9) and sensitivity (VKORC1) explain one-third of the variability in therapeutic dose before the International Normalized Ratio (INR) is measured.

Objective To provide guidance to rheumatology providers on the use of coronavirus disease 2019 (COVID‐19) vaccines for patients with rheumatic and musculoskeletal diseases (RMDs). Methods A task force was assembled that included 9 rheumatologists/immunologists, 2 infectious disease specialists, and 2 public health physicians. After agreeing on scoping questions, an evidence report was created that summarized the published literature and publicly available data regarding COVID‐19 vaccine efficacy and safety, as well as literature for other vaccines in RMD patients. Task force members rated their agreement with draft consensus statements on a 9‐point numerical scoring system, using a modified Delphi process and the RAND/University of California Los Angeles Appropriateness Method, with refinement and iteration over 2 sessions. Consensus was determined based on the distribution of ratings. Results Despite a paucity of direct evidence, 74 draft guidance statements were developed by the task force and agreed upon with consensus to provide guidance for use of the COVID‐19 vaccines in RMD patients and to offer recommendations regarding the use and timing of immunomodulatory therapies around the time of vaccination. Conclusion These guidance statements, made in the context of limited clinical data, are intended to provide direction to rheumatology health care providers on how to best use COVID‐19 vaccines and to facilitate implementation of vaccination strategies for RMD patients.

Objective. To provide guidance to rheumatology providers on the use of coronavirus disease 2019 vaccines for patients with rheumatic and musculoskeletal diseases (RMDs).Methods. A task force was assembled that included 9 rheumatologists/immunologists, 2 infectious disease specialists, and 2 public health physicians. After agreeing on scoping questions, an evidence report was created that summarized the published literature and publicly available data regarding COVID-19 vaccine efficacy and safety, as well as literature for other vaccines in RMD patients. Task force members rated their agreement with draft consensus statements on a 9-point numerical scoring system, using a modified Delphi process and the RAND/University of California Los Angeles Appropriateness Method, with refinement and iteration over 2 sessions. Consensus was determined based on the distribution of ratings.Results. Despite a paucity of direct evidence, 74 draft guidance statements were developed by the task force and agreed upon with consensus to provide guidance for use of the COVID-19 vaccines in RMD patients and to offer recommendations regarding the use and timing of immunomodulatory therapies around the time of vaccination.Conclusion. These guidance statements, made in the context of limited clinical data, are intended to provide direction to rheumatology health care providers on how to best use COVID-19 vaccines and to facilitate implementation of vaccination strategies for RMD patients.Due to the rapidly expanding information and evolving evidence related to COVID-19, which may lead to modification of some guidance statements over time, it is anticipated that updated versions of this article will be published, with the version number included in the title. Readers should ensure that they are consulting the most current version. A summary of revisions over time and their location is included in the Supplementary Tables.Guidance developed and/or endorsed by the American College of Rheumatology (ACR) is intended to inform particular patterns of practice and not to dictate the care of a particular patient. The ACR considers adherence to this guidance to be voluntary, with the ultimate determination regarding its application to be made by the physician in light of each patient's individual circumstances. Guidance statements are intended to promote beneficial or desirable outcomes but cannot guarantee any specific outcome. Guidance developed or endorsed by the ACR is subject to periodic revision as warranted by the evolution of medical knowledge, technology, and practice.

IMPORTANCE Warfarin use accounts for more medication-related emergency department visits among older patients than any other drug. Whether genotype-guided warfarin dosing can prevent these adverse events is unknown.OBJECTIVE To determine whether genotype-guided dosing improves the safety of warfarin initiation. DESIGN, SETTING, AND PATIENTSThe randomized clinical Genetic Informatics Trial (GIFT) of Warfarin to Prevent Deep Vein Thrombosis included patients aged 65 years or older initiating warfarin for elective hip or knee arthroplasty and was conducted at 6 US medical centers. Enrollment began in April 2011 and follow-up concluded in October 2016.INTERVENTIONS Patients were genotyped for the following polymorphisms: VKORC1-1639G>A, CYP2C9*2, CYP2C9*3, and CYP4F2 V433M. In a 2 × 2 factorial design, patients were randomized to genotype-guided (n = 831) or clinically guided (n = 819) warfarin dosing on days 1 through 11 of therapy and to a target international normalized ratio (INR) of either 1.8 or 2.5. The recommended doses of warfarin were open label, but the patients and clinicians were blinded to study group assignment. MAIN OUTCOMES AND MEASURESThe primary end point was the composite of major bleeding, INR of 4 or greater, venous thromboembolism, or death. Patients underwent a screening lower-extremity duplex ultrasound approximately 1 month after arthroplasty. RESULTS Among 1650 randomized patients (mean age, 72.1 years [SD, 5.4 years]; 63.6% women; 91.0% white), 1597 (96.8%) received at least 1 dose of warfarin therapy and completed the trial (n = 808 in genotype-guided group vs n = 789 in clinically guided group). A total of 87 patients (10.8%) in the genotype-guided group vs 116 patients (14.7%) in the clinically guided warfarin dosing group met at least 1 of the end points (absolute difference, 3.9% [95% CI, 0.7%-7.2%], P = .02; relative rate [RR], 0.73 [95% CI, 0.56-0.95]). The numbers of individual events in the genotype-guided group vs the clinically guided group were 2 vs 8 for major bleeding (RR, 0.24; 95% CI, 0.05-1.15), 56 vs 77 for INR of 4 or greater (RR, 0.71; 95% CI, 0.51-0.99), 33 vs 38 for venous thromboembolism (RR, 0.85; 95% CI, 0.54-1.34), and there were no deaths.CONCLUSIONS AND RELEVANCE Among patients undergoing elective hip or knee arthroplasty and treated with perioperative warfarin, genotype-guided warfarin dosing, compared with clinically guided dosing, reduced the combined risk of major bleeding, INR of 4 or greater, venous thromboembolism, or death. Further research is needed to determine the cost-effectiveness of personalized warfarin dosing.

Immune checkpoint inhibitors (ICIs) are monoclonal antibodies that target inhibitory molecules, such as cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), programmed cell death protein 1 (PD-1), or its ligand, programmed cell death protein ligand 1 (PD-L1), and lead to immune activation in the tumor micro-environment. ICIs can induce durable treatment responses in patients with advanced cancers, but they are commonly associated with immune related adverse events (irAEs) such as rash, colitis, hepatitis, pneumonitis, and endocrine and musculoskeletal disorders. Almost all patients experience some form of irAE, but high grade irAEs occur in approximately half of those on combination therapy (eg, anti-CTLA-4 plus anti-PD-1), and up to one quarter receiving ICI monotherapy. Fatal irAEs occur in approximately 1.2% of patients on CTLA-4 blockade and 0.4% of patients receiving PD-1 or PD-L1 blockade, and case fatality rates are highest for myocarditis and myositis. IrAEs typically occur in the first three months after ICI initiation, but can occur as early as one day after the first dose to years after ICI initiation. The mainstay of treatment is with corticosteroids, but tumor necrosis factor inhibitors are commonly used for refractory irAEs. Although ICIs are generally discontinued when high grade irAEs occur, ICI discontinuation alone is rarely adequate to resolve irAEs. Consensus guidelines have been published to help guide management, but will likely be modified as our understanding of irAEs grows.

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Background Race is an important predictor of TKA outcomes in the United States; however, analyses of race can be confounded by socioeconomic factors, which can result in difficulty determining the root cause of disparate outcomes after TKA. Questions/purposes We asked: (1) Are race and socioeconomic factors at the individual level associated with patient-reported pain and function 2 years after TKA? (2) What is the interaction between race and community poverty and patient-reported pain and function 2 years after TKA? Methods We identified all patients undergoing TKA enrolled in a hospital-based registry between 2007 and 2011 who provided 2-year outcomes and lived in New York, Connecticut, or New Jersey. Of patients approached to participate in the registry, more than 82% consented and provided baseline data, and of these patients, 72% provided This work was funded by the Clinical and Translational Science Center at Weill Cornell (UL1TR000457-06) (SMG), the Agency for Healthcare Research and Quality Grant U18 HS016075 (SMG), and the Block Family Foundation (SMG). One of the authors certifies that he (MPF), or a member of his immediate family, has or may receive payments or benefits, during the study period, in an amount of USD 100,001-USD 1,000,000, from Zimmer Biomet (Warsaw, IN, USA), and an amount of USD 10,000-USD 100,000 from Lima (Arlington, TX, USA). One of the authors certifies that he (MLP), or a member of his immediate family, has or may receive payments or benefits, during the study period, an amount of USD 10,000-USD 100,000 from Zimmer Biomet (Warsaw, IN, USA) related to this work. One or more of the authors certify that he (JTN), or a member of his immediate family, has or may receive payments or benefits, during the study period, an amount of less than USD 10,000 from the National Center for Advancing Translational Sciences (Bethesda, MD, USA) related to this work. One or more of the authors certify that she (Y-YL), or a member of her immediate family, has or may receive payments or benefits, during the study period, an amount of USD 10,000-USD 100,000 from the National Center for Advancing Translational Sciences ((Bethesda, MD, USA) related to this work. All ICMJE Conflict of Interest Forms for authors and Clinical Orthopaedics and Related Research 1 editors and board members are on file with the publication and can be viewed on request. Each author certifies that his or her institution approved the human protocol for this investigation, that all investigations were conducted in conformity with ethical principles of research, and that informed consent for participation in the study was obtained. 123Clin Orthop Relat Res (2016) 474:1986-1995 DOI 10.1007 Clinical Orthopaedics and Related Research ® A Publication of The Association of Bone and Joint Surgeons® 2-year data. Proportions of patients with complete followup at 2 years were lower among blacks (57%) than whites (74%), among patients with Medicaid insurance (51%) compared with patients without Medicaid insurance (72%), and among pa...