Faculty Bibliography

Gout prevalence is increasing, yet management remains suboptimal. Fortunately, new insights into gout biology are permitting the development of novel, potentially more effective strategies for both gouty inflammation and urate lowering. Colchicine, a drug long used for gout, has been recently approved (for the first time ever) by the FDA, based on a new, safer dosing regimen. The recently appreciated centrality of IL-1beta in acute gouty inflammation has prompted studies of agents blocking the IL-1beta receptor or soluble IL-1beta signaling (canakinumab, rilonacept, anakinra). Novel approaches to urate lowering have led to mechanism-based therapies such as urate synthesis inhibitors (febuxostat is already FDA approved and BCX4208 is in development), URAT-1 inhibitors promoting renal uric acid excretion (lesinurad), and recombinant uricase to directly catabolize urate (pegloticase). These new treatments do not obviate the need for lifestyle and dietary management, another area in which significant scientific and clinical progress has recently been made.

In 2012 the American College of Rheumatology (ACR) established its first-ever gout treatment guidelines. These guidelines address whom to treat, how to treat, and lifestyle and medication changes to make when treating patients with gout. In this manuscript, we review the ACR guide- lines, with special attention to the issues of treating to target, and when and how to prevent attacks during urate- lowering therapy. Given that the quality of gout treatment in the USA is often suboptimal poor, these guidelines have the potential to improve the health of millions of gout sufferers in the USA and around the world.

OBJECTIVE.: To profile the subgingival oral microbiota abundance and diversity in never-treated, new-onset rheumatoid arthritis (NORA) patients. METHODS.: Periodontal disease (PD) status, clinical activity and sociodemographic factors were determined in patients with NORA, chronic RA (CRA) and healthy subjects. Massively parallel pyrosequencing was used to compare the composition of subgingival microbiota and establish correlations between presence/abundance of bacteria and disease phenotypes. Anti-P. gingivalis antibodies were tested to assess prior exposure. RESULTS.: The more advanced forms of periodontitis are already present at disease onset in NORA patients. The subgingival microbiota of NORA is distinct from controls. In most cases, however, these differences can be attributed to PD severity and are not inherent to RA. The presence and abundance of P. gingivalis is directly associated with PD severity as well, is not unique to RA, and does not correlate with anti-citrullinated peptide antibody (ACPA) titers. Overall exposure to P. gingivalis is similar in RA and controls, observed in 78.4% and 83.3%, respectively. Anaeroglobus geminatus correlated with ACPA/RF presence. Prevotella and Leptotrichia species are the only characteristic taxa in the NORA group irrespective of PD status. CONCLUSIONS.: NORA patients exhibit a high prevalence of PD at disease onset, despite their young age and paucity of smoking history. The subgingival microbiota of NORA patients is similar to CRA and healthy subjects of comparable PD severity. Although colonization with P. gingivalis correlates with PD severity, overall exposure is similar among groups. The role of A. geminatus and Prevotella/Leptotrichia species in this process merits further study.

OBJECTIVE: The ability of antiinflammatory strategies to alter cardiovascular risk has not been rigorously examined. Colchicine is an antiinflammatory agent that affects macrophages, neutrophils, and endothelial cells, all of which are implicated in the pathogenesis of cardiovascular disease. We examined whether colchicine use was associated with a reduced risk of myocardial infarction (MI) in patients with gout. METHODS: We conducted a retrospective, cross-sectional study of all patients with an International Classification of Diseases, 9th ed, code for gout in the electronic medical record (EMR) of the New York Harbor Healthcare System Veterans Affairs network and >/= 1 hospital visit between August 2007 and August 2008. Hospital pharmacy data were used to identify patients who had filled at least 1 colchicine prescription versus those who had not. Demographics and CV comorbidities were collected by EMR review. The primary outcome was diagnosis of MI. Secondary outcomes included all-cause mortality and C-reactive protein (CRP) level. RESULTS: In total, 1288 gout patients were identified. Colchicine (n = 576) and no colchicine (n = 712) groups had similar baseline demographics and serum urate levels. Prevalence of MI was 1.2% in the colchicine versus 2.6% in the no-colchicine group (p = 0.03). Colchicine users also had fewer deaths and lower CRP levels, although these did not achieve statistical significance. Colchicine effects persisted when allopurinol users were excluded from the analysis. CONCLUSION: In this hypothesis-generating study, gout patients who took colchicine had a significantly lower prevalence of MI and exhibited trends toward reduced all-cause mortality and lower CRP level versus those who did not take colchicine.

BACKGROUND: Each year, rheumatology programs across the country teach incoming trainees the skill of arthrocentesis, but the relative effectiveness of various teaching techniques has not been assessed in a systematic way. OBJECTIVES: We compared approaches to teaching arthrocentesis using cadavers versus anatomic models. METHODS: In a pilot study, new rheumatology fellows (n = 7) from 2 academic institutions were surveyed at 3 points during arthrocentesis training: (1) before assuming patient care; (2) after lecture with handouts, followed by practice either on cadavers (group A) or on synthetic joint models (group B); and (3) 6 weeks into fellowship. Fellows rated their comfort levels for arthrocentesis of specific joints using 9-point Likert scales. Fellows also retrospectively rated the utility of individual teaching modalities in helping them to learn. As a follow-up study, internal medicine residents taking part in a month-long rheumatology rotation were similarly surveyed on their comfort level performing knee and shoulder arthrocentesis before a cadaver teaching laboratory and at the end of their month rotation. RESULTS: The initial mean comfort level performing arthrocentesis for all fellows was low (2.01). After the cadaver teaching session, group A fellows experienced an overall comfort level increase of 1.95, with the largest single increase reported for shoulder arthrocentesis (3.86). After the anatomic model teaching session, group B fellows reported a mean comfort increase of 1.29, with the largest increase reported for knee arthrocentesis (3.13). The subsequent study with residents confirmed significant increases in comfort after the cadaver laboratory. When surveyed, the learning experience fellows considered most effective was the opportunity to perform procedures under supervision and guidance, followed by training on cadavers. CONCLUSIONS: Although all teaching interventions for trainees learning arthrocentesis were helpful for increasing trainee's comfort with arthrocentesis, the use of cadavers seemed to be superior to synthetic anatomic models or lectures alone. The specific impact of these teaching interventions on actual competence, defined as a performance outcome, deserves additional study.