Oral Health in Rheumatoid Arthritis: Listening to Patients.

INTRODUCTION: Rates of periodontal disease and tooth loss are increased in individuals with rheumatoid arthritis (RA). Understanding factors that contribute to the increased burden of periodontal disease in RA is critical to improving oral health and arthritis outcomes. OBJECTIVES: To determine the perceptions held by people with RA relating to their oral health, to identify patient-centered priorities for oral health research, and to inform optimal strategies for delivering oral health knowledge. METHODS: Semistructured interviews were conducted with patients with RA. Recorded interview transcripts were iteratively reviewed to reveal surface and latent meaning and to code for themes. Constructs were considered saturated when no new themes were identified in subsequent interviews. We report themes with representative quotes. RESULTS: Interviews were conducted with 11 individuals with RA (10 women [91%]; mean age, 68 y), all of whom were taking RA medication. Interviews averaged 19 min (range, 8 to 31 min) and were mostly conducted face-to-face. Three overall themes were identified: 1) knowledge about arthritis and oral health links; 2) oral health care in RA is complicated, both in personal hygiene practices and in professional oral care; and 3) poor oral health is a source of shame. Participants preferred to receive oral health education from their rheumatologists or dentists. CONCLUSIONS: People with RA have unique oral health perceptions and experience significant challenges with oral health care due to their arthritis. Adapting oral hygiene recommendations and professional oral care delivery to the needs of those with arthritis are patient priorities and are required to improve satisfaction regarding their oral health. KNOWLEDGE TRANSLATION STATEMENT: Patients living with long-standing rheumatoid arthritis described poor oral health-related quality of life and multiple challenges with maintaining optimal oral health. Study findings indicate a need for educational materials addressing oral health maintenance for patients with rheumatic diseases and their providers.

Rising incidence of psychiatric disorders before diagnosis of immune-mediated inflammatory disease.

AIMS: After the diagnosis of immune-mediated inflammatory diseases (IMID) such as inflammatory bowel disease (IBD), multiple sclerosis (MS) and rheumatoid arthritis (RA), the incidence of psychiatric comorbidity is increased relative to the general population. We aimed to determine whether the incidence of psychiatric disorders is increased in the 5 years before the diagnosis of IMID as compared with the general population. METHODS: Using population-based administrative health data from the Canadian province of Manitoba, we identified all persons with incident IBD, MS and RA between 1989 and 2012, and cohorts from the general population matched 5 : 1 on year of birth, sex and region to each disease cohort. We identified members of these groups with at least 5 years of residency before and after the IMID diagnosis date. We applied validated algorithms for depression, anxiety disorders, bipolar disorder, schizophrenia, and any psychiatric disorder to determine the annual incidence of these conditions in the 5-year periods before and after the diagnosis year. RESULTS: We identified 12 141 incident cases of IMID (3766 IBD, 2190 MS, 6350 RA) and 65 424 matched individuals. As early as 5 years before diagnosis, the incidence of depression [incidence rate ratio (IRR) 1.54; 95% CI 1.30-1.84) and anxiety disorders (IRR 1.30; 95% CI 1.12-1.51) were elevated in the IMID cohort as compared with the matched cohort. Similar results were obtained for each of the IBD, MS and RA cohorts. The incidence of bipolar disorder was elevated beginning 3 years before IMID diagnosis (IRR 1.63; 95% CI 1.10-2.40). CONCLUSION: The incidence of psychiatric comorbidity is elevated in the IMID population as compared with a matched population as early as 5 years before diagnosis. Future studies should elucidate whether this reflects shared risk factors for psychiatric disorders and IMID, a shared final common inflammatory pathway or other aetiology.

Markedly increased incidence of critical illness in adults with Type 1 diabetes.

AIMS: To compare the incidence of and mortality after intensive care unit admission in adults with paediatric-onset Type 1 diabetes vs the general population. METHODS: Using population-based administrative data from Manitoba, Canada, we identified 814 cases of paediatric-onset Type 1 diabetes, and 3579 general population controls matched on age, sex and region of residence. We estimated the incidence of intensive care unit admission in adulthood, and compared the findings between populations using incidence rate ratios and multivariable Cox proportional hazards regression, adjusting for age, sex, comorbidity and socio-economic status. We estimated age- and sex-standardized mortality rates after intensive care unit admission. RESULTS: Between January 2000 and October 2009, the average annual incidence of intensive care unit admission among prevalent cohorts was 910 per 100 000 in the Type 1 diabetes population, and 106 per 100 000 in matched controls, an eightfold increased risk (incidence rate ratio 8.6; 95% CI 5.5, 14.0). The adjusted risk of intensive care unit admission was elevated to a greater extent among women with Type 1 diabetes compared with matched women (hazard ratio 14.7; 95% CI 7.2, 29.4) than among men with Type 1 diabetes compared with matched men (hazard ratio 4.92; 95% CI 10.3, 2.36) The most common reasons for admission in the diabetes cohort were diabetic ketoacidosis, infection and ischaemic heart disease. At 30%, 5-year mortality was higher in the diabetes cohort than in the matched cohort (relative risk 5.7; 95% CI 1.2, 8.9). CONCLUSIONS: Compared with the general population, the risk of intensive care unit admission was higher in adults with paediatric-onset Type 1 diabetes, and mortality after admission was also higher.

Role of Anti-Carbamylated Protein Antibodies Compared to Anti-Citrullinated Protein Antibodies in Indigenous North Americans With Rheumatoid Arthritis, Their First-Degree Relatives, and Healthy Controls.

OBJECTIVE: Rheumatoid arthritis (RA) is characterized by the presence of autoantibodies, including seropositivity for rheumatoid factor (RF) and anti-citrullinated protein antibodies (ACPAs). In addition, antibodies to carbamylated proteins (anti-CarP) are present in patients with RA and are associated with joint damage. This study was undertaken to assess the presence of anti-CarP antibodies in indigenous North Americans (First Nations [FN] populations) with RA compared to their at-risk first-degree relatives (FDRs) and healthy controls. METHODS: Anti-CarP IgG and ACPAs (specifically, anti-cyclic citrullinated peptide [anti-CCP] antibodies) were measured by enzyme-linked immunosorbent assay in the sera of FN patients with RA (n = 95), their unaffected FDRs (n = 109), and healthy FN controls (n = 85). Antibodies to additional citrullinated peptides were measured using a multiplex ACPA array, and the number of peptides recognized was reported as an ACPA score. Groups were compared using the chi-square test and Mann-Whitney U test. Associations between RA and seropositivity for RF, ACPAs, and anti-CarP antibodies were determined by logistic regression. RESULTS: Anti-CarP antibodies were more frequent in FN patients with RA (44.3%) compared to FDRs (18.3%) and FN controls (4.7%) (both P < 0.0001 versus RA). Moreover, anti-CarP antibodies were more frequent in FDRs than in FN controls (P = 0.008). The ACPA score was higher in anti-CCP-positive FN patients with RA than in anti-CCP-positive FN FDRs (median score 7 [interquartile range (IQR) 7] versus median score 1 [IQR 4]; P = 0.04). The association with RA was strongest when all 3 autoantibodies (RF, anti-CCP, and anti-CarP) were present in the patients' serum (odds ratio 194, 95% confidence interval 23-1,609, P < 0.0001). CONCLUSION: Anti-CarP antibodies are prevalent in FN patients with RA and also more common in their at-risk FDRs compared to healthy controls. The results indicate an association of RF, ACPAs, and anti-CarP with RA that is strongest when all 3 autoantibodies are present. These findings may provide new insights into the evolution of autoimmunity in preclinical RA.

Determining the Minimally Important Difference in the Clinical Disease Activity Index for Improvement and Worsening in Early Rheumatoid Arthritis Patients.

OBJECTIVE: Simplified measures to quantify rheumatoid arthritis (RA) disease activity are increasingly used. The minimum clinically important differences (MCID) for some measures, such as the Clinical Disease Activity Index (CDAI), have not been well-defined in real-world clinic settings, especially for early RA patients with low/moderate disease activity. METHODS: Data from Canadian Early Arthritis Cohort patients were used to examine absolute change in CDAI in the first year after enrollment, stratified by disease activity. MCID cut points were derived to optimize the sum of sensitivity and specificity versus the gold standard of patient self-reported improvement or worsening. Sensitivity, specificity, positive predictive values, and negative predictive values were calculated against patient self-reported improvement (gold standard) and for change in pain, Health Assessment Questionnaire (HAQ), and Disease Activity Score in 28 joints (DAS28) improvement. Discrimination was examined using the area under receiver operator curves. Similar methods were used to evaluate MCIDs for worsening for patients who achieved low disease activity. RESULTS: A total of 578 patients (mean ± SD age 54.1 ± 15.3 years, 75% women, median [interquartile range] disease duration 5.3 [3.3, 8.0] months) contributed 1,169 visit pairs to the improvement analysis. The MCID cut points for improvement were 12 (patients starting in high disease activity: CDAI >22), 6 (moderate: CDAI 10-22), and 1 (low disease activity: CDAI <10). Performance characteristics were acceptable using these cut points for pain, HAQ, and DAS28. The MCID for CDAI worsening among patients who achieved low disease activity was 2 units. CONCLUSION: These minimum important absolute differences in CDAI can be used to evaluate improvement and worsening and increase the utility of CDAI in clinical practice.

Sm antibodies increase risk of death in systemic lupus erythematosus.

The importance of ethnicity, socioeconomic status (SES), and autoantibodies as prognostic indicators in lupus were evaluated in a Canadian cohort. A retrospective review of 330 lupus patients identified demographic features including age and self reported ethnicity, SES, lupus features, antibodies to extractable nuclear antigens (ENAs), organ damage (SDI score), and mortality. ENA (Sm, RNP, Ro, La) associations with lupus features, predictors of final visit SDI score and the contributions of ethnicity, autoantibodies and SES on overall mortality were determined. Three ethnic groups [Caucasians (C), Asian-Orientals (AO), Native American First Nations (FN)] differed in disease severity and SES. FN and AO patients had similarly severe lupus, developing lupus at an earlier age, with more renal and neurological involvement, greater SDI scores at last visit, and more frequently had Sm or RNP antibodies than C. FN had the highest mortality and lowest SES. Sm and RNP antibodies were associated with renal and neurologic involvement. RNP, education and duration of follow-up predicted SDI score. Sm increased risk of death. In conclusion, RNP and lower SES are associated with lupus related organ damage and the presence of Sm is a predictor of mortality in lupus, independent of ethnicity, renal involvement or socioeconomic status.

Hepatitis B vaccination for patients with chronic renal failure.

BACKGROUND: Chronic renal failure patients are at particular risk of hepatitis B virus infection. Early studies have demonstrated that renal failure patients benefit from vaccination; however, not all studies have consistently shown benefit. OBJECTIVES: To determine the beneficial and harmful effects of hepatitis B vaccine and of a reinforced vaccination series in chronic renal failure patients. SEARCH STRATEGY: We searched The Cochrane Hepato-Biliary Group Controlled Trials Register, The Cochrane Renal Group Controlled Trials Register, The Cochrane Controlled Trials Register on The Cochrane Library (Issue 1, 2002),PubMed/MEDLINE (1966 to July 2003), EMBASE (1985 to November 2003), Current Clinical Practice Guidelines (Canadian Immunization Guide and Vaccine Preventable Diseases Surveillance Manual), and Science Citation Index as well as journals, published abstracts, and reference lists of articles. SELECTION CRITERIA: Randomised clinical trials comparing plasma vaccine with placebo, recombinant vaccine with placebo, recombinant vaccine with plasma vaccine, and a reinforced vaccination series (ie, more than three inoculations) with three inoculations of vaccine in chronic renal failure patients. DATA COLLECTION AND ANALYSIS: Primary outcome measures included incidence of patients developing hepatitis B virus antibodies and infections while secondary outcomes included adverse events, liver-related morbidity, and mortality. Random effects models were used and reported relative risks and 95% confidence intervals (RR and 95% CI). MAIN RESULTS: We included seven randomised clinical trials. None of them had high quality. Plasma vaccine was significantly more effective than placebo in achieving hepatitis B antibodies (RR 23.0, 95% CI 14.39 to 36.76, 3 trials). We found no statistically significant difference between plasma vaccine or placebo regarding hepatitis B virus infections (RR 0.50, 95% CI 0.20 to 1.24). We found no statistically significant differences between recombinant vaccine and plasma vaccine in achieving hepatitis B antibodies (RR 0.65, 95% CI 0.28 to 1.53, 2 trials). Heterogeneity was significant and appeared to be attributable to the dose of vaccine. Two trials examined a reinforced recombinant vaccine strategy, which was not statistically more effective than three inoculations of recombinant vaccine regarding development of hepatitis B antibodies (RR 1.36, 95% CI 0.85 to 2.16). REVIEWERS' CONCLUSIONS: Plasma derived vaccines are more effective than placebo in achieving hepatitis B antibodies, while no statistically significant difference was found between recombinant and plasma vaccines. No statistically significant difference of effectiveness was observed between a reinforced vaccination series versus routine vaccinations of three inoculations of recombinant vaccine.

Infrared spectroscopy: shedding light on synovitis in patients with rheumatoid arthritis.

OBJECTIVES: It is difficult to determine the extent of synovial involvement early in the course of rheumatoid arthritis. A spectroscopic technique was used to characterize the synovium of the small finger joints in both early and late rheumatoid arthritis. This synovium was also compared against normal joints. METHODS: Near-infrared spectroscopy assesses the absorption of near-infrared light by specific joints, giving a characteristic "fingerprint" of the properties of the underlying tissues. Triple measurements by infrared spectroscopy were taken at the bilateral second and third metacarpophalangeal joints. Multivariate analysis was applied. RESULTS: Analysis was able to demonstrate relationships between the specific sources of spectral variation and joint tenderness or swelling as well as radiographic damage. Further use of multivariate analysis allowed recognition of the spectral patterns seen in early disease vs late rheumatoid arthritis and correct classification of over 74% of the joints. CONCLUSIONS: The spectral regions where differences occurred were in the absorption bands related to tissue oxygenation status, allowing the provocative implication that this technique could be detecting ischaemic changes within the joint. Near-infrared spectroscopy may thus be able to provide us with some information about the biochemical changes associated with synovitis.

The histopathology of early synovitis.

Early diagnosis and therapeutic intervention are needed to prevent the morbidity related to erosive arthropathies such as rheumatoid arthritis (RA), yet it is difficult to distinguish various forms of synovitis early in the disease course. The availability of synovial tissue biopsy techniques has facilitated the analysis of synovial tissue from patients with early disease. Comparison of the histopathologic features of synovial tissue in early RA, established RA, and in non-RA synovitis has shown subtle, but potentially important differences in histologic features, cytokine and protease expression patterns, and apoptosis. Ultimately, it remains to be shown definitively that analysis of the histopathological features of synovial tissue early in disease is of independent value in identifying patients destined to have persistent synovitis or erosive disease, and in turn, in allocating patients to specific therapeutic strategies.