Methotrexate Treatment of Newly Diagnosed RA Patients Is Associated With DNA Methylation Differences at Genes Relevant for Disease Pathogenesis and Pharmacological Action

Background: Methotrexate (MTX) is the fi rst line treatment of rheumatoid arthritis (RA), and methylation changes in bulk T cells have been reported after treatment with MTX. We have investigated cell-type speci fi c DNA methylation changes across the genome in naïve and memory CD4 + T cells before and after MTX treatment of RA patients. DNA methylation pro fi les of newly diagnosed RA patients (N=9) were assessed by reduced representation bisul fi te sequencing. Results: We found that MTX treatment signi fi cantly in fl uenced DNA methylation levels at multiple CpG sites in both cell populations. Interestingly, we identi fi ed differentially methylated sites annotated to two genes; TRIM15 and SORC2, previously reported to predict treatment outcome in RA patients when measured in bulk T cells. Furthermore, several of the genes, including STAT3, annotated to the signi fi cant CpG sites are relevant for RA susceptibility or the action of MTX. Conclusion: We detected CpG sites that were associated with MTX treatment in CD4 + naïve and memory T cells isolated from RA patients. Several of these sites overlap genetic regions previously associated with RA risk and MTX treatment outcome

Antibiotic prescribing in nursing homes in an area with low prevalence of antibiotic resistance: Compliance with national guidelines

Objective. To examine antibiotic prescribing in nursing homes and determine to what degree the prescribing was in accordance with the national guidelines for antibiotic prescribing. Design. Retrospective examination of patients’ records who were prescribed antibiotics in the period 1 March 2007 to 28 February 2008. Setting and patients. Patients residing in the nursing homes of Arendal, Norway. Main outcome measures. Choice of antibiotic in respect of the recommendations in the national guidelines for antibiotic prescribing. Results. A total of 714 antibiotic courses were prescribed to 327 patients yielding a prevalence of 6.6%. Compliant prescribing was 77% for urinary tract infections (UTI), 79% for respiratory tract infections (RTI), and 76% for skin and soft tissue infections (SSTI). Ciprofloxacin was responsible for 63% of non-compliant prescribing. On the respite wards there was a higher rate of total prescribing, non-compliant prescribing, and prescribing by physicians employed at the local hospital. Conclusion. Guidelines for antibiotic use must be implemented actively and efforts to improve antibiotic prescribing in nursing homes must be aimed at both nursing home and hospital physicians