Low prevalence of work disability in early inflammatory arthritis (EIA) and early rheumatoid arthritis at enrollment into a multi-site registry: results from the catch cohort.

We determined the prevalence of work disability in early rheumatoid arthritis (ERA) and undifferentiated early inflammatory arthritis (EIA) patients at first enrollment into the Canadian Early Arthritis Cohort (CATCH) who met the 2010 ACR criteria versus those not meeting criteria, to determine the impact of meeting new criteria on work disability status. Data at first visit into the cohort were analyzed. Descriptive statistics and logistic regression analyses were performed to investigate the association of other variables in our database with work disability. 1,487 patients were enrolled in the CATCH study, a multi-site observational, prospective cohort of patients with EIA. 934 patients were excluded (505 based on missing criteria for ACR 2010 classification, as anti-CCP was absent, and 429 were not working for other reasons). Of the 553 patients included, 71 % were female with mean disease duration of 6.4 months. 524 (94.8 %) were employed while 29 (5.2 %) reported work disability at first visit. There were no differences between those meeting 2010 ACR criteria versus those who did not. Baseline characteristics associated with work disability were male gender, age, education, income, HAQ, and positive RF status. The mean HAQ score in work disabled patients was 1.4 versus 0.9 in those who were working (p < 0.001). Disease activity score (DAS28) was not associated with work disability (p = 0.069), nor was tender joint count, swollen joint count, anti-CCP, patient global assessment, or SF-12v2. In the regression model, work disability was associated with lower income levels (p = 0.01) and worse HAQ scores (OR 2.33; p = 0.001), but not significantly associated with male gender (p = 0.08), older age (>50 years; p = 0.3), lower education (p = 0.3) or RF positivity (p = 0.6). We found rates of work disability to be low at entry into this EIA cohort compared to previous studies. There may be potential for intervention in ERA to prevent the development of work disability.

A two-tier model of polymyxin B resistance in Burkholderia cenocepacia.

Burkholderia cenocepacia is an environmental bacterium causing serious human opportunistic infections and is extremely resistant to multiple antibiotics including antimicrobial peptides, such as polymyxin B (PmB). Extreme antibiotic resistance is attributed to outer membrane impermeability ('intrinsic' resistance). Previous work showed that production of full-length lipopolysaccharide (LPS) prevents surface binding of PmB. We hypothesized that two tiers of resistance mechanisms rendering different thresholds of PmB resistance exist in B. cenocepacia. To test this notion, candidate genes were mutated in two isogenic strains expressing full-length LPS or truncated LPS devoid of heptose ('heptoseless LPS') respectively. We uncovered various proteins required for PmB resistance only in the strain with heptoseless LPS. These proteins are not involved in preventing PmB binding to whole cells or permeabilization of the outer membrane. Our results support a two-tier model of PmB resistance in B. cenocepacia. One tier sets a very high threshold mediated by the LPS and the outer membrane permeability barrier. The second tier sets a lower threshold that may play a role in PmB resistance only when outer membrane permeability is compromised. This model may be of general applicability to understanding the high antimicrobial peptide resistance of environmental opportunistic pathogens.