Harlan Sayles

Porphyromonas gingivalis and Disease-Related Autoantibodies in Individuals at Increased Risk of Rheumatoid Arthritis

OBJECTIVE To examine the relationship of Porphyromonas gingivalis to the presence of autoantibodies in individuals at risk of rheumatoid arthritis (RA). METHODS Study participants included the following: 1) a cohort enriched in subjects with HLA-DR4 and 2) subjects at risk of RA by virtue of having a first-degree relative with RA. None of the study subjects satisfied the American College of Rheumatology 1987 classification criteria for RA. Autoantibodies measured included anti-citrullinated protein antibody (ACPA; by second-generation anti-cyclic citrullinated peptide antibody enzyme-linked immunosorbent assay [ELISA]) and rheumatoid factor (RF; by nephelometry or ELISA for IgA, IgM, or IgG isotype). Individuals were considered autoantibody positive (n = 113) if they had ≥1 RA-related autoantibody; individuals were further categorized as high risk (n = 38) if they had ACPA or positive findings ≥2 assays for RF. Autoantibody-negative individuals (n = 171) served as a comparator group. Antibody to P gingivalis, P intermedia, and F nucleatum were measured. Associations of bacterial antibodies with group status were examined using logistic regression. RESULTS Anti-P gingivalis concentrations were higher in high-risk (P = 0.011) and autoantibody positive group (P = 0.010) than in the autoantibody negative group. There were no group differences in anti-P intermedia or anti-F nucleatum concentrations. After multivariable adjustment, anti-P gingivalis concentrations (but not anti-P intermedia or anti-F nucleatum) were significantly associated with autoantibody-positive and high-risk status (P < 0.05). CONCLUSION Immunity to P gingivalis, but not P intermedia or F nucleatum, is significantly associated with the presence of RA-related autoantibodies in individuals at risk of RA. These results support the hypothesis that infection with P gingivalis may play a central role in the early loss of tolerance to self antigens that occurs in the pathogenesis of RA.

Rheumatoid factor as a potentiator of anti-citrullinated protein antibody-mediated inflammation in rheumatoid arthritis

The co‐occurrence of rheumatoid factor (RF) and anti–citrullinated protein antibody (ACPA) positivity in rheumatoid arthritis (RA) is well described. However, the mechanisms underlying the potential interaction between these 2 distinct autoantibodies have not been well defined. The aim of this study was to evaluate the epidemiologic and molecular interaction of ACPAs and RF and its association with both disease activity and measures of RA‐associated inflammation.

Associations of disease activity and treatments with mortality in men with rheumatoid arthritis: results from the VARA registry

OBJECTIVES To examine the all-cause mortality rate and factors associated with mortality in US veteran men with RA. METHODS Men with RA were enrolled and followed until death or censoring. Vital status was ascertained through systematic record review and standardized mortality ratios (SMRs) were calculated using US life tables for men. Multivariate Cox proportional hazards regression was used to examine the independent associations of patient factors including socio-demographics, comorbidity, measures of RA disease activity/severity and medication use with mortality. Measures of RA disease activity and medications were examined as time-varying factors. RESULTS A total of 138 deaths were observed during 2314 patient-years of follow-up (n=1015 patients), corresponding to a crude morality rate of 5.9 deaths per 100 patient-years (95% CI 5.0, 7.0) and an SMR of 2.1 (95% CI 1.8, 2.5). After multivariate adjustment, factors independently associated with higher mortality risk in men with RA included older age, Caucasian race, low body weight, an increased frequency of rheumatology visits, higher ESR and RF concentrations, increased DAS28, subcutaneous nodules and prednisone use. In contrast, MTX use [hazard ratio (HR) 0.63; 95% CI 0.42, 0.96] was associated with ∼40% lower mortality risk. CONCLUSION Mortality rates among US male veterans with RA are more than twice those of age-matched men in the general population. These results suggest that optimizing disease control, particularly with regimens that include MTX and minimize glucocorticoid exposure, could improve long-term survival in this population.

Associations of cigarette smoking with rheumatoid arthritis in African Americans

OBJECTIVE To examine the associations of cigarette smoking with rheumatoid arthritis (RA) in African Americans, and to determine whether this association is impacted by the HLA-DRB1 shared epitope (SE). METHODS Smoking status, cumulative smoking exposure, and SE status were determined in African American patients with RA and African American healthy controls. Associations of smoking with RA were examined using age- and sex-adjusted logistic regression analyses. Additive and multiplicative SE-smoking interactions were examined. RESULTS After adjustment for age and sex, ever smoking (odds ratio [OR] 1.45, 95% confidence interval [95% CI] 1.07, 1.97) and current smoking (OR 1.56, 95% CI 1.07, 2.26), relative to never smoking, were more common in African American patients with RA (n = 605) than in controls (n = 255). The association of smoking with RA was limited to those with a cumulative exposure exceeding 10 pack-years, associations that were evident both in autoantibody-positive and in autoantibody-negative disease. There was evidence of a significant additive interaction between SE status and heavy smoking (≥10 pack-years) in relation to RA risk (attributable proportion [AP] due to interaction 0.58, P = 0.007), with similar results for the additive interaction between SE status and ever smoking (AP 0.47, P = 0.006). There was no evidence of multiplicative interactions. CONCLUSION Among African Americans, cigarette smoking is associated not only with the risk of autoantibody-positive RA but also with the risk of autoantibody-negative disease. The risk of RA attributable to smoking is limited to African Americans with more than 10 pack-years of exposure and is more pronounced among individuals positive for the HLA-DRB1 SE.

Malondialdehyde-Acetaldehyde Adducts and Anti–Malondialdehyde-Acetaldehyde Antibodies in Rheumatoid Arthritis

Malondialdehyde‐acetaldehyde (MAA) adducts are a product of oxidative stress associated with tolerance loss in several disease states. This study was undertaken to investigate the presence of MAA adducts and circulating anti‐MAA antibodies in patients with rheumatoid arthritis (RA).

Implementation of a Clinical Decision Support System for Antimicrobial Stewardship

Clinical decision support systems (CDSSs) for antimicrobial stewardship require considerable human resources and financial investments. This pre-/postimplementation study evaluated the effect of a CDSS on performance of prospective audit with intervention and feedback and demonstrated an increase in interventions and recommendation acceptance countered by a substantial number of nonactionable alerts.

Long-acting parenteral nanoformulated antiretroviral therapy: interest and attitudes of HIV-infected patients

AIM To gauge patient interest in receiving long-acting injectable nanoformulated antiretroviral therapy. METHODS Four hundred adult HIV-infected patients currently prescribed antiretroviral therapy were surveyed. χ(2) tests were used for comparisons of interest across groups. RESULTS Respondents were 68% male and 53% African-American, with a mean age of 47 years. Overall, 73% of patients indicated that they would definitely or probably try injectable nanoformulated antiretroviral therapy; 61% with weekly dosing; 72% every 2 weekly; and 84% monthly. In total, 48% indicated that they were very concerned about the possible side effects and 35% were very concerned about needle use. CONCLUSION The majority of respondents indicated that they definitely or probably would try parenteral nanoformulated antiretroviral therapy.

Prevention of depression with escitalopram in patients undergoing treatment for head and neck cancer: randomized, double-blind, placebo-controlled clinical trial.

IMPORTANCE Major depressive disorder develops in up to half the patients undergoing treatment for head and neck cancer, resulting in significant morbidity; therefore, preventing depression during cancer treatment may be of great benefit. OBJECTIVE To determine whether prophylactic use of the antidepressant escitalopram oxalate would decrease the incidence of depression in patients receiving primary therapy for head and neck cancer. DESIGN, SETTING, AND PARTICIPANTS A randomized, double-blind, placebo-controlled trial of escitalopram vs placebo was conducted in a group of nondepressed patients diagnosed as having head and neck cancer who were about to enter cancer treatment. Patients were stratified by sex, site, stage (early vs advanced), and primary modality of treatment (radiation vs surgery). MAIN OUTCOME AND MEASURE The primary outcome measure was the number of participants who developed moderate or greater depression (scores on the Quick Inventory of Depressive Symptomology-Self Rated of ≥11). RESULTS From January 6, 2008, to December 28, 2011, 148 patients were randomized. Significantly fewer patients receiving escitalopram developed depression (24.6% in the placebo group vs 10.0% in the escitalopram group; stratified log-rank test, P = .04). A Cox proportional hazards regression model compared the 2 treatment groups after controlling for age, baseline smoking status, and stratification variables. The hazard ratio of 0.37 (95% CI, 0.14-0.96) demonstrated an advantage of escitalopram (P = .04). Patients undergoing radiotherapy as the initial modality were significantly more likely to develop depression than those undergoing surgery (radiotherapy compared with surgery group; hazard ratio, 3.6; 95% CI, 1.38-9.40; P = .009). Patients in the escitalopram group who completed the study and were not depressed rated their overall quality of life as significantly better for 3 consecutive months after cessation of drug use. CONCLUSIONS AND RELEVANCE In nondepressed patients undergoing treatment for head and neck cancer, prophylactic escitalopram reduced the risk of developing depression by more than 50%. In nondepressed patients who completed the trial, quality of life was also significantly better for 3 consecutive months after cessation of drug use in the escitalopram group. These findings have important implications for the treatment of patients with head and neck cancer. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00536172.

Associations of Hydroxychloroquine Use With Lipid Profiles in Rheumatoid Arthritis: Pharmacologic Implications

To evaluate the association of hydroxychloroquine (HCQ) use with lipid profiles in a Veterans Affairs Rheumatoid Arthritis (VARA) cohort.

Validation of the rheumatic disease comorbidity index.

There is no consensus on which comorbidity index is optimal for rheumatic health outcomes research. We compared a new Rheumatic Disease Comorbidity Index (RDCI) with the Charlson‐Deyo Index (CDI), Functional Comorbidity Index (FCI), Elixhauser Total Score (ETS), Elixhauser Point System (EPS), and a simple comorbidity count (COUNT) using a US cohort of rheumatoid arthritis (RA) patients.