Faculty Bibliography

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.

After nearly 50 years, new drugs are now available or in development for gout. Febuxostat (approved 2009) selectively inhibits xanthine oxidase, preventing uric acid formation and lowering serum urate. Pegloticase (approved 2010) is a recombinant chimeric mammalian uricase that corrects the intrinsic human uricase deficiency. Pegloticase reduces serum urate, and may have particular efficacy against tophi. IL-1beta is now understood to be a central actor in acute gouty inflammation. Three IL-1beta antagonists - anakinra, rilonacept and canakinumab (all US FDA approved for other uses) - are being evaluated for gout treatment and/or prophylaxis. The renal urate resorbing transporters URAT1 and GLUT9 have been recently characterized as targets of uricosuric drugs; two pipeline drugs, RDEA594 and tranilast, inhibit these transporters and are promising urate-lowering therapies. 2011 Future Science Ltd

Many drugs can cause myopathies, and such myopathies may range widely from asymptomatic elevations in the serum creatine phosphokinase levels to severe myalgias, cramps, exercise intolerance, muscle weakness, and even rhabdomyolysis. In this article, some of the commonly used drugs that may induce myopathies, as well as the clinical phenotypes, diagnosis, and management of these syndromes are reviewed

BACKGROUND: Patients with gout have comorbidities, but the impact of these comorbidities on treatment has not been studied. METHODS: A total of 575 patients with gout were stratified according to certainty of diagnosis according to International Classification of Diseases, 9th Revision, Clinical Modification code alone (cohort I), American College of Radiology criteria (cohort II), and crystal diagnosis (cohort III). Comorbid conditions were defined according to International Classification of Diseases, 9th Revision, Clinical Modification codes, and stratified as either moderate or severe. Drug contraindications were defined as moderate or strong, based on Food and Drug Administration criteria and severity of disease. RESULTS: The most common comorbidity was hypertension (prevalence 0.89). The presence of comorbidities resulted in a high frequency of contraindications to approved gout medications. More than 90% of patients had at least 1 contraindication to nonsteroidal anti-inflammatory drugs. Many patients demonstrated multiple contraindications to 1 or more gout medications. Frequently, patients were prescribed medications to which they harbored contraindications. The prevalence of patients prescribed colchicine despite having at least 1 strong contraindication was 30% (cohort I), 37% (cohort II), and 39.6% (cohort III). CONCLUSION: Patients with gout typically harbor multiple comorbidities that result in contraindications to many of the medications available to treat gout. Frequently, despite contraindications to gout therapies, patients are frequently prescribed these medications