North American musculoskeletal ultrasound scanning protocol of the shoulder, elbow, wrist, and hand: update of a Delphi Consensus Study.

INTRODUCTION/OBJECTIVES: There has been an increase in the proficiency and utilization of ultrasound among North American rheumatologists over the past decade. This study aims to create an updated upper extremity scanning protocol to inform ultrasound curriculum development for the American College of Rheumatology affiliated fellowship programs and guide clinical practice patterns in North America. METHOD: Three Delphi survey rounds were used to reach consensus on tiered-mastery designations for scan views of the shoulder, elbow, wrist, and hand joints. The survey was disseminated by Qualtrics™ to 101 potential participants with ultrasound experience. High agreement was defined as having ≥ 85% consensus and final tier designation as > 50% agreement for a preferred tier. Changes in responses were evaluated by McNemar's chi-square test. RESULTS: Consensus was achieved for 70% of scan views of the upper extremity joints. Two views-ulnar transverse view of the wrist and the radial/ulnar orthogonal views over metacarpophalangeal joints 2 and 5 of the hand-were upgraded from tier 2 to tier 1. The suprascapular transverse and the axillary longitudinal views of the shoulder were downgraded from tier 2 to tier 3. A new anterior transverse view of the elbow was added to the protocol with tier 1 designation. CONCLUSIONS: This study reflects the current opinions of North American rheumatologists for scanning upper extremity joints and provides support for the updated protocol and guidance for educators in rheumatology ultrasound. Key Points • Ultrasound scan views of the metacarpophalangeal, wrist, elbow, and glenohumeral joint recesses and views of the biceps and rotator cuff tendons at the shoulder were perceived as essential views of the upper extremity scanning protocol for rheumatologists to master and perform routinely. • A targeted scanning approach of the upper extremity joints may be considered when focal symptoms are present. • The North American Musculoskeletal Ultrasound Scanning Protocol shares some similarities with existing musculoskeletal ultrasound protocols of other specialties and worldwide rheumatology societies but varies in the extent of examination and emphasis on certain specialty-specific focuses.

Comparative Effectiveness of Allopurinol and Febuxostat in Gout Management.

BACKGROUND: The relative efficacy and safety of allopurinol and febuxostat when used according to current guidelines for the treatment of hyperuricemia are unknown. This double-blind noninferiority trial examined these issues. METHODS: Participants with gout and hyperuricemia (with at least 33% having stage 3 chronic kidney disease) were randomly assigned to allopurinol or febuxostat in this 72-week trial, with doses titrated to target serum urate. The trial had three phases: titration (weeks 0 to 24), maintenance (weeks 25 to 48), and observation (weeks 49 to 72). Allopurinol and febuxostat were initiated at daily doses of 100 and 40 mg, with maximum titration to 800 and 120 mg, respectively. Antiinflammatory prophylaxis was given during phases 1 and 2. The primary end point was the proportion of patients experiencing one or more flares during phase 3, with a prespecified noninferiority margin of less than 8 percentage points between allopurinol and febuxostat. Secondary end points included efficacy in patients with chronic kidney disease, proportion achieving target serum urate levels, and serious adverse events. RESULTS: This study included 940 participants; 20.1% withdrew, with similar proportions in treatment arms. During phase 3, 36.5% of allopurinol-treated participants had one flare or more compared with 43.5% of febuxostat-treated participants (P<0.001 for noninferiority). Overall, 80% of participants achieved mean target urates during phase 2 with no differences by treatment. There were no treatment differences (including cardiovascular events) in serious adverse events. CONCLUSIONS: Allopurinol and febuxostat achieved serum urate goals in patients with gout; allopurinol was noninferior to febuxostat in controlling flares. Similar outcomes were noted in participants with stage 3 chronic kidney disease. (Funded by the Cooperative Studies Program of the Department of Veterans Affairs Office of Research and Development; ClinicalTrials.gov identifier, NCT02579096.).

Innovation in early medical education, no bells or whistles required.

BACKGROUND: Despite a paucity of evidence to support a multitude of educational innovations, curricular leaders are pressured to find innovative solutions to better prepare medical students for an evolving twenty-first century health care system. As part of this effort, this study directly compared student-rated effectiveness scores of six different learning modalities. METHODS: Study participants included 286 medical students enrolled in the second-year rheumatology core at a single academic medical center between 2013 and 2017. Students were surveyed at the end of the core with a 15-item questionnaire, and student perceived effectiveness of six different learning modalities were compared. RESULTS: The modality that outperformed all others was Live Patient Encounters (LPE), with significantly higher student-rated effectiveness scores when compared to the referent modality of Problem-Based Learning (PBL). Using a 5-point Likert scale with responses ranging from "not effective" to "highly effective," LPE received a mean effectiveness score of 4.77 followed by Augenblick (4.21), PBL (4.11), Gout Racer video game (3.49), Rheumatology Remedy e-module (3.49), and simulation knee injection (3.09). CONCLUSIONS: Technologically advanced novel learning strategies were outperformed in this study by the more traditional active learning modality of LPE. This finding highlights the importance of testing innovative learning strategies at the level of the learner. Three additional conclusions can be drawn from this result. First, conflation of technology with innovation may lead to a myopic view of educational reform. Second, human factors seem to be responsible for the success of LPE and may have far-reaching educational rewards. Third, further applications of LPE should be tested in non-rheumatologic curricula. The relevance of this study is innately tied to the humanities-based application. While a formal qualitative analysis was not performed in this study, preliminary results suggest that live, structured patient interactions in the pre-clinical years of medical education may not only promote the learning of important educational objectives but also foster professional development, empathy, reflection, leadership, agency, and interpersonal skills. This "win-win" scenario (if true) would stand out as a rarity among strategic educational initiatives.

Musculoskeletal Ultrasound Scanning Protocol Consensus Statements on Scanning Conventions and Documentation in the US.

OBJECTIVE: European rheumatology and radiology-determined standards have largely driven the execution of ultrasound in rheumatology (RhUS). How this translates to American rheumatologic practice has not been examined. A rheumatology-driven consensus on documentation, scanning conventions, and tiered-mastery designation for anatomic region views was developed in 2011 and served as the framework for training and clinical research validation. The present study was undertaken to update this consensus to reflect current utilization of musculoskeletal RhUS evaluation in the US. METHODS: A 3-round Delphi method study was conducted using a 96-item questionnaire sent via Qualtrics survey software to 101 respondents experienced in RhUS education and scholarship. The target participant number was 38. High agreement was defined as ≥85% agreement on each item. McNemar's chi-square test was used to analyze changes in agreement in the responses. Comments were reviewed for content analysis. RESULTS: A total of 46 respondents completed all 3 rounds. Of documentation and scanning convention statements, 80% and 100%, respectively, reached high agreement. Comments reflected the need for rheumatology-defined and disease-specific complete scan and limited scan definitions, separate from radiology-defined definitions. CONCLUSION: Many scanning conventions from 2011 remain relevant in current practice. There is a need to determine rheumatology-defined descriptions for common procedural terminology codes for complete and limited scans that accurately reflect the current state of RhUS.

Musculoskeletal Ultrasound Instruction in Adult Rheumatology Fellowship Programs.

OBJECTIVE: Musculoskeletal ultrasound (MSUS) in rheumatology in the US has advanced by way of promotion of certifications and standards of use and inclusion of core fellowship curriculum. In order to inform endeavors for curricular integration, the objectives of the present study were to assess current program needs for curricular incorporation and the teaching methods that are being employed. METHODS: A needs-assessment survey (S1) was sent to 113 rheumatology fellowship program directors. For programs that taught MSUS, a curriculum survey (S2) was sent to lead faculty. Programs were stratified according to program size and use of a formal written curriculum. RESULTS: S1 (108 of 113 respondents; response rate 96%) revealed that 94% of programs taught MSUS, with 41% having a curriculum. Curricular implementation was unaffected by program size. Formal curricular adoption of MSUS was favored by 103 directors (95.3%), with 65.7% preferring such adoption to be optional. S2 (74 of 101 respondents; response rate 73%) showed that 41% of programs utilized a formal curriculum. Multiple teaching strategies were used, with content that was generally similar. Use of external courses, including the Ultrasound School of North American Rheumatologists course, was prevalent. Fewer barriers were noted compared to past surveys, but inadequate time, funding, and number of trained faculty still remained. Lack of divisional interest (P = 0.046) and interest of fellows (P = 0.012) were noted among programs without a formal curriculum. CONCLUSION: MSUS is taught by a significantly larger number of rheumatology fellowship programs today. Multiple teaching strategies are used with common content, and barriers still remain for some programs. Most program directors favor inclusion of a standardized MSUS curriculum, with many favoring inclusion to be optional.

Generalizability of Patients With Rheumatoid Arthritis in Biologic Agent Clinical Trials.

OBJECTIVE: Randomized controlled trials (RCTs) have consistently demonstrated the efficacy of biologic agents in treating patients with rheumatoid arthritis (RA) who satisfy strict eligibility criteria, yet studies report that a majority of RA patients in the US have had biologic treatment exposure. We identified the proportion of RA patients in clinical practice satisfying entry criteria for biologic agent RCTs. METHODS: Eligibility criteria of 30 RCTs of 10 Food and Drug Administration-approved biologic agents to treat RA were reviewed, summarized, and applied to 2 observational clinical cohorts: the Veterans Affairs Rheumatoid Arthritis registry (VARA; n = 1,523) and the Rheumatology and Arthritis Investigational Network Database (RAIN-DB; n = 1,548). Patients at a single clinical encounter were assessed for overall trial eligibility as well as eligibility across 3 domains: demographics, disease activity, and medication exposure. RESULTS: The mean percentage of patients that satisfied eligibility criteria was 3.7% (interquartile range [IQR] 1.5-3.1) in VARA and 7.1% (IQR 4.4-7.7) in RAIN-DB. Ineligibility was most often due to low disease activity, specifically low joint counts. The mean Disease Activity Score in 28 joints at enrollment was 6.59 (range 6.1-7.1) across RCTs versus 3.87 (0.07-8.69) in VARA and 3.65 (0.49-7.21) in RAIN-DB. RCTs for non-tumor necrosis factor (TNF) inhibitor biologic agents were more restrictive than RCTs for TNF inhibitors. There was no trend in eligibility by RCT study publication or drug approval date. CONCLUSION: The vast majority of RA patients from our clinical cohorts did not satisfy criteria for participation in biologic agent RCTs. These findings underscore the need for caution in extrapolating trial results to day-to-day management of RA patients and may provide insight into the differential responses to biologic agents reported in prior observational studies.

Cardiovascular risk and the use of biologic agents in rheumatoid arthritis.

Although patients with rheumatoid arthritis (RA) are recognized to be disproportionately impacted by cardiovascular disease (CVD), effective approaches of primary and secondary CVD prevention have not been well defined in this population. Given their robust disease-modifying potential and effects on both pro-inflammatory and pro-atherogenic pathways, there has been substantial speculation that biologic treatments may serve as a means of providing highly effective RA disease control while simultaneously reducing CVD risk in this high risk group. In this review, we examine available evidence relevant to the associations of approved biologic treatments with CVD outcomes in the context of RA.

Musculoskeletal ultrasound objective structured clinical examination: an assessment of the test.

OBJECTIVE: To determine the reliability and validity of an objective structured clinical examination (OSCE) for musculoskeletal ultrasound (MSUS). METHODS: A 9-station OSCE was administered to 35 rheumatology fellows trained in MSUS and to 3 expert faculty (controls). Participants were unaware of joint health (5 diseased/4 healthy). Faculty assessors (n = 9) graded image quality with predefined checklists and a 0-5 global rating, blinded to who performed the study. Interrater reliability, correlation between a written multiple choice question examination (MCQ) and OSCE performance, and comparison of fellow OSCE results with those of the faculty were measured to determine OSCE reliability, concurrent validity, and construct validity. RESULTS: Assessors' interrater reliability was good (intraclass correlation coefficient [ICC] 0.7). Score reliability was good in the normal wrist and ankle stations (ICC 0.7) and moderate in the abnormal wrist and ankle stations (ICC 0.4). MCQ grades significantly correlated with OSCE grades (r = 0.52, P < 0.01). The fellows in the bottom quartile of the MCQ scored 3.07 on the OSCE, significantly worse than the top quartile fellows (3.32) and the faculty (3.29; P < 0.01). Scores also significantly discriminated bottom quartile fellows from faculty in the normal wrist and ankle stations (3.38 versus 3.78; P < 0.01), but not in the abnormal stations (3.37 versus 3.49; P = 0.08). CONCLUSION: MSUS OSCE is a reliable and valid method for evaluation of MSUS skill. Normal joint assessment stations are more reliable than abnormal joint assessment stations and better discriminate poorly performing fellows from faculty. Therefore, MSUS OSCE with normal joints can be used for the assessment of MSUS skill competency.

Regional distribution of adult rheumatologists.

OBJECTIVE: To analyze the distribution of rheumatology practices in the US and factors associated with that distribution, in order to better understand the supply of the rheumatology workforce. METHODS: Using the American College of Rheumatology membership database, all practicing adult rheumatologist office addresses were mapped with ArcView software. The number of rheumatologists per Core Based Statistical Area (CBSA) was calculated. To investigate whether sociodemographic factors correlated with clustering of rheumatologists, covariates from the 2010 US Census for each CBSA, including age, sex, race/ethnicity, and median household income, were modeled. RESULTS: Many CBSAs, predominantly smaller micropolitan areas, did not have a practicing rheumatologist. For some of these smaller micropolitan areas (with populations of at least 40,000), the closest practicing rheumatologist was more than 200 miles away. However, we also identified several more-populous areas (populations of 200,000 or more) without a practicing rheumatologist. Greater numbers of rheumatologists were more likely to practice in areas with higher population densities and higher median incomes. More rheumatologists were also found in CBSAs in which there were rheumatology training programs. CONCLUSION: These findings demonstrate that many smaller regions of the country have no or few practicing adult rheumatologists. Patients with chronic rheumatic conditions in these areas likely have limited access to rheumatology care. Policy changes could address potential regional rheumatology workforce shortages, but limitations of the current data would need to be addressed prior to implementation of such changes.

Therapies for active rheumatoid arthritis after methotrexate failure.

BACKGROUND: Few blinded trials have compared conventional therapy consisting of a combination of disease-modifying antirheumatic drugs with biologic agents in patients with rheumatoid arthritis who have active disease despite treatment with methotrexate--a common scenario in the management of rheumatoid arthritis. METHODS: We conducted a 48-week, double-blind, noninferiority trial in which we randomly assigned 353 participants with rheumatoid arthritis who had active disease despite methotrexate therapy to a triple regimen of disease-modifying antirheumatic drugs (methotrexate, sulfasalazine, and hydroxychloroquine) or etanercept plus methotrexate. Patients who did not have an improvement at 24 weeks according to a prespecified threshold were switched in a blinded fashion to the other therapy. The primary outcome was improvement in the Disease Activity Score for 28-joint counts (DAS28, with scores ranging from 2 to 10 and higher scores indicating more disease activity) at week 48. RESULTS: Both groups had significant improvement over the course of the first 24 weeks (P=0.001 for the comparison with baseline). A total of 27% of participants in each group required a switch in treatment at 24 weeks. Participants in both groups who switched therapies had improvement after switching (P<0.001), and the response after switching did not differ significantly between the two groups (P=0.08). The change between baseline and 48 weeks in the DAS28 was similar in the two groups (-2.1 with triple therapy and -2.3 with etanercept and methotrexate, P=0.26); triple therapy was noninferior to etanercept and methotrexate, since the 95% upper confidence limit of 0.41 for the difference in change in DAS28 was below the margin for noninferiority of 0.6 (P=0.002). There were no significant between-group differences in secondary outcomes, including radiographic progression, pain, and health-related quality of life, or in major adverse events associated with the medications. CONCLUSIONS: With respect to clinical benefit, triple therapy, with sulfasalazine and hydroxychloroquine added to methotrexate, was noninferior to etanercept plus methotrexate in patients with rheumatoid arthritis who had active disease despite methotrexate therapy. (Funded by the Cooperative Studies Program, Department of Veterans Affairs Office of Research and Development, and others; CSP 551 RACAT ClinicalTrials.gov number, NCT00405275.)

Antibody responses to Porphyromonas gingivalis (P. gingivalis) in subjects with rheumatoid arthritis and periodontitis.

UNLABELLED: Antibody titers to P. gingivalis are increased in patients with rheumatoid arthritis and are associated with disease-specific autoimmunity. BACKGROUND: Periodontitis (PD) has been implicated as a risk factor for rheumatoid arthritis (RA). We sought to characterize antibody titers to P. gingivalis (a pathogen in PD) in subjects with RA, PD, and in healthy controls and to examine their relationship with disease autoantibodies. METHODS: P. gingivalis antibody was measured in subjects with RA (n=78), PD (n=39), and in controls (n=40). Group frequencies of bacterial titer elevations were compared using the Chi-square test and antibody titers were compared using non-parametric tests. Correlations of P. gingivalis titer with C-reactive protein (CRP), antibody to cyclic citrullinated peptide (anti-CCP), and rheumatoid factor (RF) were examined in those with RA while CRP and autoantibody concentrations were compared based on seropositivity to P. gingivalis. RESULTS: Antibody titers to P. gingivalis were highest in PD, lowest in controls, and intermediate in RA (p=0.0003). Elevations in P. gingivalis (titer> or =800) were more common in RA and PD (67% and 77%, respectively) than in controls (40%) (p=0.002). In RA, there were significant correlations with P. gingivalis titer with CRP, anti-CCP-IgM, and -IgG-2. CRP (p=0.006), anti-CCP-IgM (p=0.01) and -IgG2 (p=0.04) concentrations were higher in RA cases with P. gingivalis titers > or =800 compared to cases with titers <800. CONCLUSION: Antibodies to P. gingivalis are more common in RA subjects than controls, although lower than that in PD. Associations of P. gingivalis titers with RA-related autoantibody and CRP concentrations suggests that infection with this organism plays a role in disease risk and progression in RA.

Early rheumatoid arthritis: pitfalls in diagnosis and review of recent clinical trials.

The treatment of rheumatoid arthritis (RA) has changed dramatically in the past decade as advancements in the understanding of the pathobiology of the disease have led to novel therapeutic agents. The recognition that early diagnosis and treatment leads to improvements in morbidity and mortality has altered the therapeutic strategy such that early therapy is now considered the standard of care. This review focuses on the challenges in making the diagnosis of early RA, including a broad differential diagnosis for inflammatory polyarthritis, poor performance of the standard classification criteria, difficulty in clinical assessment of synovitis, absence of absolute laboratory tests, inability of conventional radiography to detect bony changes early, and barriers to rheumatology care. Additionally, the pathogenesis of RA is highlighted, with particular emphasis on cytokine biology as it relates to therapeutic regimens. Relevant clinical trials in early RA are reviewed and discussed, including trials of combination disease-modifying antirheumatic drugs and biological therapy. The role of induction therapy as a novel therapeutic approach is highlighted. The search for predictors of response is reviewed and the external validity of the trials is analysed. Finally, the trials in early RA therapy suggest that swift intervention with combinations of medications is required for patients with severe RA. However, further research is needed to determine which regimen is appropriate for the individual patient with RA.

Understanding treatments for gout.

Gout is one of the most readily manageable of the rheumatic diseases. This article reviews basic pathways in purine metabolism, uric acid handling, and the pathogenic mechanism of clinical gout, as well as the areas in those pathways amenable to intervention. Attention is also given to associated comorbidities, such as hyperuricemia and obesity, hypertension, hyperinsulinemia, and coronary artery disease. The significance of lifestyle modifications, such as weight loss and alcohol reduction, is discussed as an important adjunct to pharmacotherapy in gout. Current and investigational agents used in gout management are also reviewed. Finally, treatment recommendations for acute and chronic gout are suggested.

Is there still a role for traditional disease-modifying antirheumatic drugs (DMARDs) in rheumatoid arthritis?

Rheumatoid arthritis is a chronic and debilitating disease, affecting an estimated 1% of the population worldwide. The past decade has witnessed an explosion in our understanding of the pathophysiology of rheumatoid arthritis and therefore in our ability to more effectively target the disease process. Although a cure remains elusive, remission is an approachable goal. There has been a complete remodeling of the traditional "pyramid" by rheumatologists, who now treat rheumatoid arthritis earlier and more aggressively than ever before. Standard single therapy with disease-modifying antirheumatic drugs, which was previously the final step in treating rheumatoid arthritis, is now practically bypassed in the deluge of information suggesting that combinations of disease-modifying antirheumatic drugs or newer biologic therapy is more effective. It is difficult to assimilate all the data and develop a rational approach; however, the bottom line is often the deciding factor: the newer agents are tremendously expensive. The intent of this article is to review recent and relevant trials in the treatment of rheumatoid arthritis, suggest a treatment algorithm, and argue that traditional disease-modifying antirheumatic drugs continue to play a pivotal role.