Antibodies to citrullinated proteins and differences in clinical progression of rheumatoid arthritis

Antibodies to citrullinated proteins (anti-cyclic-citrullinated peptide [anti-CCP] antibodies) are highly specific for rheumatoid arthritis (RA) and precede the onset of disease symptoms, indicating a pathogenetic role for these antibodies in RA. We recently showed that distinct genetic risk factors are associated with either anti-CCP-positive disease or anti-CCP-negative disease. These data are important as they indicate that distinct pathogenic mechanisms are underlying anti-CCP-positive disease or anti-CCP-negative disease. Likewise, these observations raise the question of whether anti-CCP-positive RA and anti-CCP-negative RA are clinically different disease entities. We therefore investigated whether RA patients with anti-CCP antibodies have a different clinical presentation and disease course compared with patients without these autoantibodies. In a cohort of 454 incident patients with RA, 228 patients were anti-CCP-positive and 226 patients were anti-CCP-negative. The early symptoms, tender and swollen joint count, and C-reactive protein level at inclusion, as well as the swollen joint count and radiological destruction during 4 years of follow-up, were compared for the two groups. There were no differences in morning stiffness, type, location and distribution of early symptoms, patients' rated disease activity and C-reactive protein at inclusion between RA patients with and without anti-CCP antibodies. The mean tender and swollen joint count for the different joints at inclusion was similar. At follow-up, patients with anti-CCP antibodies had more swollen joints and more severe radiological destruction. Nevertheless, the distribution of affected joints, for swelling, bone erosions and joint space narrowing, was similar. In conclusion, the phenotype of RA patients with or without anti-CCP antibodies is similar with respect to clinical presentation but differs with respect to disease course

Leflunomide in the treatment of patients with early rheumatoid arthritis—results of a prospective non-interventional study

Leflunomide is effective and well tolerated in the treatment of rheumatoid arthritis (RA), however, data on its use in early RA are scarce. This study seeks to evaluate effectiveness and safety of leflunomide in the treatment of early RA in daily practice. This prospective, open-label, non-interventional, multi-center study was carried out over 24 weeks including adults with early RA (≤1 year since diagnosis). Leflunomide treatment was according to label instructions. Three hundred thirty-four patients were included. Disease activity score in 28 joints (DAS28) response (reduction in DAS28 of >1.2 or reduction of >0.6 and a DAS28 of ≤5.1) was 71.9% at week 12 and 84.6% at week 24. 25.0% of patients achieved clinical remission (DAS28 ≤ 2.6). Most frequently reported adverse drug reactions (ADR) were diarrhea (3.0%), nausea (2.4%), hypertension (1.8%), and headache (1.5%). Serious ADR were reported in four patients (1.2%). Leflunomide showed the effectiveness which was to be expected from controlled studies without revealing any new or hitherto unknown side effects. Onset of action was quick and significant improvement of disease was seen after 12 weeks of therapy and at even higher rates after 24 weeks irrespective of the use of a loading dose. Interestingly, the DAS28-remission rate achieved was similar to the rate seen with methotrexate or biologic therapy in other studies

Antimalarial Therapy Selection for Quinolone Resistance among Escherichia coli in the Absence of Quinolone Exposure, in Tropical South America

BACKGROUND: Bacterial resistance to antibiotics is thought to develop only in the presence of antibiotic pressure. Here we show evidence to suggest that fluoroquinolone resistance in Escherichia coli has developed in the absence of fluoroquinolone use. METHODS: Over 4 years, outreach clinic attendees in one moderately remote and five very remote villages in rural Guyana were surveyed for the presence of rectal carriage of ciprofloxacin-resistant gram-negative bacilli (GNB). Drinking water was tested for the presence of resistant GNB by culture, and the presence of antibacterial agents and chloroquine by HPLC. The development of ciprofloxacin resistance in E. coli was examined after serial exposure to chloroquine. Patient and laboratory isolates of E. coli resistant to ciprofloxacin were assessed by PCR-sequencing for quinolone-resistance-determining-region (QRDR) mutations. RESULTS: In the very remote villages, 4.8% of patients carried ciprofloxacin-resistant E. coli with QRDR mutations despite no local availability of quinolones. However, there had been extensive local use of chloroquine, with higher prevalence of resistance seen in the villages shortly after a Plasmodium vivax epidemic (p<0.01). Antibacterial agents were not found in the drinking water, but chloroquine was demonstrated to be present. Chloroquine was found to inhibit the growth of E. coli in vitro. Replica plating demonstrated that 2-step QRDR mutations could be induced in E. coli in response to chloroquine. CONCLUSIONS: In these remote communities, the heavy use of chloroquine to treat malaria likely selected for ciprofloxacin resistance in E. coli. This may be an important public health problem in malarious areas

Real patient learning integrated in a preclinical block musculoskeletal disorders. Does it make a difference?

Although musculoskeletal disorders are the most common reason for general practitioner visits, training did not keep pace. Implementation of learning from patients with rheumatologic disorders linked together with the teaching of theoretical knowledge in the preclinical medical education might be an important step forward in the improvement of quality of care for these patients. The Leiden Medical School curriculum has implemented two non-obligatory real patient learning (RPL) practicals integrated within the preclinical block musculoskeletal disorders. This study investigates the educational effectiveness of the practicals, the expectations students have of RPL, and students’ satisfaction. Participants’ grades on the end-of-block test served as the test results of the educational effectiveness of the practicals and were compared with those of the non-participants. Qualitative data was collected by means of questionnaires generated by focus groups. The participants in practicals scored significantly higher at the end-of-block test. The expected effects of the contact with real patients concerned positive effects on cognition and skills. ‘Contextualizing of the theory’, ‘better memorizing of clinical pictures’, and ‘understanding of the impact of the disease’ were the most frequently mentioned effects of the practicals. Overall, the participants were (very) enthusiastic about this educational format. The RPL practicals integrated within a preclinical block musculoskeletal disorders are a valuable addition to the Leiden medical curriculum. This relatively limited intervention exhibits a strong effect on students’ performance in tests. Future research should be directed towards the long-term effects of this intervention

Locating sex-specific evidence on clinical questions in MEDLINE: a search filter for use on OvidSP™

<p>Abstract</p> <p>Background</p> <p>Many recently published clinical studies report sex-specific data. This information may help to improve clinical decision-making for both sexes, but it is not easily accessible in MEDLINE. The aim of this project was to develop and validate a search filter that would facilitate the retrieval of studies reporting high quality sex-specific data on clinical questions.</p> <p>Methods</p> <p>A filter was developed by screening titles, abstracts and Medical Subject Headings (MeSH) in a set of 80 high quality and relevant papers, 75 of which were identified through a review of clinical guidelines and five through other means. The filter, for use on OvidSP™, consists of nine command lines for searching free text words in the title, abstract and MeSH of a paper. It was able to identify 74/80 (92.5%) of the articles from which it was derived. The filter was evaluated in a set of 622 recently published original studies on Alzheimer's disease and on asthma. It was validated against a reference of 98 studies from this set, which provided high quality, clinically relevant, sex-specific evidence. Recall and precision were used as performance measures.</p> <p>Results</p> <p>The filter demonstrated 81/98 (83%) recall and 81/125 (65%) precision in retrieving relevant articles on Alzheimer's disease and on asthma. In comparison, only 30/98 (31%) recall would have been achieved if sex-specific MeSH terms only had been used.</p> <p>Conclusion</p> <p>This sex-specific search filter performs well in retrieving relevant papers, while its precision rate is good. It performs better than a search with sex-specific MeSH. The filter can be useful to anyone seeking sex-specific clinical evidence (e.g., guideline organizations, researchers, medical educators, clinicians).</p