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Risk factors for Staphylococcus aureus bacteremia in patients with rheumatoid arthritis and incidence compared with the general population: protocol for a Danish nationwide observational cohort study
  1. Sabine Sparre Dieperink1,
  2. Bente Glintborg2,3,
  3. Louise Bruun Oestergaard4,
  4. Mette Nørgaard5,
  5. Thomas Benfield3,6,
  6. Frank Mehnert5,
  7. Andreas Petersen7,
  8. Merete Lund Hetland2,3
  1. 1 Copenhagen Center for Arthritis Research (COPECARE), Center for Rheumatology and Spine Diseases, Centre of Head and Orthopaedics, Rigshospitalet Glostrup, Glostrup, Denmark
  2. 2 The DANBIO registry and Copenhagen Center for Arthritis Research (COPECARE), Center for Rheumatology and Spine Diseases, Centre of Head and Orthopaedics, Rigshospitalet Glostrup, Glostrup, Denmark
  3. 3 Department of Clinical Medicine, University of Copenhagen, Faculty of Health and Medical Sciences, Copenhagen, Denmark
  4. 4 Cardiovascular Research Center, Herlev and Gentofte University Hospital, Hellerup, Denmark
  5. 5 Department of Clinical Epidemiology, Aarhus University Hospital, Aarhus, Denmark
  6. 6 Department of Infectious Diseases, Hvidovre Hospital, Hvidovre, Denmark
  7. 7 Bacteria, Parasites and Fungi, Statens Serum Institut, Copenhagen, Denmark
  1. Correspondence to Dr Sabine Sparre Dieperink; sabine.sparre.dieperink{at}


Introduction Staphylococcus aureus bacteremia (SAB) is an invasive infection with high mortality and morbidity. Rheumatoid arthritis (RA) is associated with increased risk of infections due to the disease per se and the use of antirheumatic treatments. Few minor studies have previously investigated risk of SAB in patients with RA and indicated increased risk compared with the general population. This nationwide observational study aims to investigate incidence of and risk factors for SAB in adult patients with RA compared with the general population. The effect of disease characteristics (eg, joint erosions, disease duration and activity), different antirheumatic treatments and smoking on SAB risk will be evaluated.

Methods and analysis All adults (>18 years of age) alive and living in Denmark in 1996–2017 will be identified in The Danish Civil Registration System. Incident patients with RA are identified in the Danish National Patient Registry (DNPR) and the nationwide rheumatology registry, DANBIO, in which information on, for example, antirheumatic treatments, disease characteristics and smoking is collected prospectively in routine care. Information on comorbidities, invasive procedures and prescribed drugs are identified in the DNPR and in The Register of Medicinal Product Statistics. Socioeconomic status is evaluated in national registers on income and education. Incident cases of first-time SAB are identified in The Danish National SAB Database. All registers are linked on an individual level by unique civil registration numbers. Incidence rates and incidence rate ratios will be analysed using Poisson regression models and the impact of possible risk factors will be evaluated.

Ethics and dissemination All data will be handled in accordance with the General Data Protection Regulation (EU) 2016/679. No ethical approval is necessary in Denmark when handling registry data only. The results will be presented in accordance with the Strengthening the Reporting of Observational Studies in Epidemiology initiative in international peer-reviewed journals and at medical conferences.

Trial registration number NCT03908086.

  • Rheumatoid arthritis
  • Staphylococcus aureus
  • Staphylococcus aureus bacteremia
  • Antirheumatic agents
  • Bacteremia

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  • Contributors SSD conceptualised the study hypotheses. MLH, BG, MN, LBO, FM, TB and AP contributed with the further development of these and with the study design. SSD wrote the first draft of the paper, which was critically revised by the other authors.

  • Funding This work was supported by the Danish Rheumatism Association grant number R163-A5715.

  • Competing interests TB reports grants from Pfizer, grants from Novo Nordisk Foundation, grants from Simonsen Foundation, grants from GSK, personal fees from Pfizer, and BG reports grants from Pfizer, Biogen and Abbvie, all outside the submitted work.

  • Patient consent for publication Not required.

  • Provenance and peer review Not commissioned; externally peer reviewed.

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