Detecting the earliest signs of rheumatoid arthritis: symptoms and examination.

Signs and symptoms often occur well in advance of a formal diagnosis of rheumatoid arthritis (RA). However, these do not necessarily represent symptoms that are included in classification criteria. Their intensity, frequency, and persistence over time seem to be important in the spectrum from preclinical autoimmunity to classifiable RA. Prospective study of signs and symptoms in individuals at risk for RA will help to determine their onset and relationship with epitope spreading, cytokine evolution, sensitive imaging, and their usefulness in discriminating between individuals patients who will develop incident inflammatory arthritis versus normal controls.

RFC1 80G>A is a genetic determinant of methotrexate efficacy in rheumatoid arthritis: a human genome epidemiologic review and meta-analysis of observational studies.

OBJECTIVE: Associations have been reported between candidate genes and the response to methotrexate (MTX) in rheumatoid arthritis (RA) patients, but most of the studies have been small and have yielded conflicting results. This study was undertaken to provide a systematic review of all genetic variant associations with MTX efficacy and toxicity, and to conduct a meta-analysis evaluating the most commonly studied single-nucleotide polymorphism for which prior cumulative analysis has been lacking. METHODS: A systematic review and meta-analysis were performed to identify genetic variant associations with MTX efficacy and toxicity. Studies were identified from the Medline, EMBase, HuGENet Navigator, and Cochrane Library databases through December 2012, and from the 2009-2011 abstracts of the American College of Rheumatology and the European League Against Rheumatism annual meeting proceedings. Additional unpublished genotype data from a Canadian cohort of patients with early RA were also included. RESULTS: Among the 87 identified studies examining genetic associations with MTX efficacy and toxicity, the reduced folate carrier 1 gene (RFC1) variant 80G>A (Arg(27) His, rs1051266) was selected for random-effects meta-analysis. RFC1 80G>A was associated with MTX efficacy in both the recessive model (odds ratio [OR] 1.42, 95% confidence interval [95% CI] 1.04-1.93) and the additive model (OR 1.28, 95% CI 1.10-1.49). Restriction of the sensitivity analyses to studies that involved Caucasian subjects only and that used similar outcome measures (MTX failure versus nonfailure) maintained and improved the associations in both models. No significant association between RFC1 80G>A and MTX toxicity was detected. CONCLUSION: In these analyses of available data from observational studies, RFC1 80G>A was found to be associated with MTX efficacy, but not toxicity, in RA patients. This variant merits further prospective analysis as a potential predictor of MTX efficacy. Variability in the definitions of response in pharmacogenetic studies is a source of data heterogeneity that should be addressed.

HLA markers for susceptibility and expression in scleroderma.

OBJECTIVE: Reported associations between HLA alleles and both susceptibility to and features of scleroderma have been conflicting. Our objective was (1) to determine the role of HLA alleles in the susceptibility to scleroderma; and (2) to determine the role of HLA alleles in various aspects of disease expression. METHODS: Consecutive patients were followed in the scleroderma clinic between 1996 and 1998. Clinical data were obtained through chart review. Healthy volunteers as well as cadaveric donors served as controls. Molecular HLA typing was performed (polymerase chain reaction/sequence-specific oligonucleotides). Statistical analysis included Fisher's exact test and multivariate analyses, using logistic and linear regression models. RESULTS: Ninety-five Caucasian patients (75 women, 20 men, age 43.9 yrs, disease duration 11.9 yrs) with scleroderma and 416 controls were studied. HLA-DRB1*01 and HLA-DRB1*11 were associated with susceptibility to scleroderma, whereas HLA-DRB1*07 was protective. HLA-A*30 and HLA-A*32 were also associated with susceptibility to scleroderma, while HLA-B*57 and HLA-Cw*14 were protective. HLA-B*62 and HLA-DRB1*07 had a significant correlation with the presence of diffuse skin involvement in both univariate and multivariate analyses. HLA-DRB1*11 was associated with high skin score values, while lower values were related to the presence of HLA-Cw*14 and HLA-DQB1*06. Both alleles retained significance in a linear regression model. High skin score values were related to the absence of anticentromere antibodies. Pulmonary fibrosis was associated with HLA-B*62 and HLA-Cw*0602, whereas pulmonary hypertension was associated with HLA-B*13 and HLA-B*65. CONCLUSION: HLA alleles play a role in susceptibility to scleroderma and its disease expression.

Automatic referral to cardiac rehabilitation.

OBJECTIVES: Cardiac rehabilitation (CR) remains underused and inconsistently accessed, particularly for women and minorities. This study examined the factors associated with CR enrollment within the context of an automatic referral system through a retrospective chart review plus survey. Through the Behavioral Model of Health Services Utilization, it was postulated that enabling and perceived need factors, but not predisposing factors, would significantly predict patient enrollment. SUBJECTS: A random sample of all atherosclerotic heart disease (AHD) patients treated at a tertiary care center (Trillium Health Centre, Ontario, Canada) from April 2001 to May 2002 (n = 501) were mailed a survey using a modified Dillman method (71% response rate). MEASURES: Predisposing measures consisted of sociodemographics such as age, sex, ethnocultural background, work status, level of education, and income. Enabling factors consisted of barriers and facilitators to CR attendance, exercise benefits and barriers (EBBS), and social support (MOS). Perceived need factors consisted of illness perceptions (IPQ) and body mass index. RESULTS: Of the 272 participants, 199 (73.2%) attended a CR assessment. Lower denial/minimization, fewer logistical barriers to CR (eg, distance, cost), and lower perceptions of AHD as cyclical or episodic reliably predicted CR enrollment among cardiac patients who were automatically referred. CONCLUSION: Because none of the predisposing factors were significant in the final model, this suggests that factors associated with CR enrollment within the context of an automatic referral model relate to enabling factors and perceived need. A prospective controlled evaluation of automatic referral is warranted.