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- Askling, J, et al.
(författare)
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Haematopoietic malignancies in rheumatoid arthritis : lymphoma risk and characteristics after exposure to tumour necrosis factor antagonists
- 2005
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Ingår i: Annals of the Rheumatic Diseases. - : BMJ. - 0003-4967 .- 1468-2060. ; 64:10, s. 1414-1420
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND:Patients with rheumatoid arthritis (RA) are at increased risk of malignant lymphomas, and maybe also of leukaemia and multiple myeloma. The effect of tumour necrosis factor (TNF) antagonists on lymphoma risk and characteristics is unclear.OBJECTIVE:To assess expected rates and relative risks of haematopoietic malignancies, especially those associated with TNF antagonists, in large population based cohorts of patients with RA.METHODS:A population based cohort study was performed of patients with RA (one prevalent cohort (n = 53,067), one incident cohort (n = 3703), and one TNF antagonist treated cohort 1999 through 2003 (n = 4160)), who were linked with the Swedish Cancer Register. Additionally, the lymphoma specimens for the 12 lymphomas occurring in patients with RA exposed to TNF antagonists in Sweden 1999 through 2004 were reviewed.RESULTS:Study of almost 500 observed haematopoietic malignancies showed that prevalent and incident patients with RA were at increased risk of lymphoma (SIR = 1.9 and 2.0, respectively) and leukaemia (SIR = 2.1 and 2.2, respectively) but not of myeloma. Patients with RA treated with TNF antagonists had a tripled lymphoma risk (SIR = 2.9) compared with the general population. After adjustment for sex, age, and disease duration, the lymphoma risk after exposure to TNF antagonists was no higher than in the other RA cohorts. Lymphomas associated with TNF antagonists had characteristics similar to those of other RA lymphomas.CONCLUSION:Overall, patients with RA are at equally increased risks for lymphomas and leukaemias. Patients with RA treated with TNF antagonists did not have higher lymphoma risks than other patients with RA. Prolonged observation is needed to determine the long term effects of TNF antagonists on lymphoma risk.
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- Askling, J, et al.
(författare)
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Risks of solid cancers in patients with rheumatoid arthritis and after treatment with tumour necrosis factor antagonists
- 2005
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Ingår i: Annals of the Rheumatic Diseases. - : BMJ. - 0003-4967 .- 1468-2060. ; 64:10, s. 1421-1426
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND:Existing studies of solid cancers in rheumatoid arthritis (RA) reflect cancer morbidity up until the early 1990s in prevalent cohorts admitted to hospital during the 1980s.OBJECTIVE:To depict the cancer pattern of contemporary patients with RA, from updated risk data from prevalent and incident RA populations. To understand the risk of solid cancer after tumour necrosis factor (TNF) treatment by obtaining cancer data from cohorts treated in routine care rather than trials.METHODS:A population based study of three RA cohorts (one prevalent, admitted to hospital 1990-2003 (n = 53,067), one incident, diagnosed 1995-2003 (n = 3703), and one treated with TNF antagonists 1999-2003 (n = 4160)), which were linked with Swedish nationwide cancer and census registers and followed up for cancer occurrence through 2003.RESULTS:With 3379 observed cancers, the prevalent RA cohort was at marginally increased overall risk of solid cancer, with 20-50% increased risks for smoke related cancers and +70% increased risk for non-melanoma skin cancer, but decreased risk for breast (-20%) and colorectal cancer (-25%). With 138 cancers, the incident RA cohort displayed a similar cancer pattern apart from non-decreased risks for colorectal cancer. TNF antagonist treated patients displayed solid cancer (n = 67) risks largely similar to those of other patients with RA.CONCLUSION:The cancer pattern in patients treated with TNF antagonists mirrors those of other contemporary as well as historic RA cohorts. The consistent increase in smoking associated cancers in patients with RA emphasises the potential for smoking cessation as a cancer preventive measure in RA.
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- Askling, Johan, et al.
(författare)
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Anti-tumour necrosis factor therapy in rheumatoid arthritis and risk of malignant lymphomas : relative risks and time trends in the Swedish Biologics Register
- 2009
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Ingår i: Annals of the Rheumatic Diseases. - London, UK : BMJ. - 0003-4967 .- 1468-2060. ; 68:5, s. 648-653
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND:Tumour necrosis factor (TNF) antagonists have proved effective as treatment against rheumatoid arthritis (RA), but the unresolved issue of whether the use of anti-TNF therapy increases the already elevated risk of lymphoma in RA remains a concern.METHODS:Using the Swedish Biologics Register (ARTIS), the Swedish Cancer Register, pre-existing RA cohorts and cross-linkage with other national health and census registers, a national RA cohort (n = 67,743) was assembled and patients who started anti-TNF therapy between 1998 and July 2006 (n = 6604) were identified. A general population comparator (n = 471,024) was also assembled and the incidence of lymphomas from 1999 to 31 December 2006 was assessed and compared in these individuals.RESULTS:Among the 6604 anti-TNF-treated RA patients, 26 malignant lymphomas were observed during 26,981 person-years of follow-up, which corresponded to a relative risk (RR) of 1.35 (95% CI 0.82 to 2.11) versus anti-TNF-naive RA patients (336 lymphomas during 365,026 person-years) and 2.72 (95% CI 1.82 to 4.08) versus the general population comparator (1568 lymphomas during 3,355,849 person-years). RA patients starting anti-TNF therapy in 1998-2001 accounted for the entire increase in lymphoma risk versus the two comparators. By contrast, RR did not vary significantly by time since start of first treatment or with the accumulated duration of treatment, nor with the type of anti-TNF agent.CONCLUSION:Overall and as used in routine care against RA, TNF antagonists are not associated with any major further increase in the already elevated lymphoma occurrence in RA. Changes in the selection of patients for treatment may influence the observed risk.
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- Briggs, Karen K, et al.
(författare)
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The reliability, validity, and responsiveness of the Lysholm score and Tegner activity scale for anterior cruciate ligament injuries of the knee
- 2009
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Ingår i: American Journal of Sports Medicine. - : Sage Publications. - 0363-5465 .- 1552-3365. ; 37:5, s. 890-897
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Tidskriftsartikel (refereegranskat)abstract
- Background: In 1982, the Lysholm score was first published as a physician-administered score in the American Journal of Sports Medicine. The Tegner activity scale was published in 1985.Hypothesis: The Lysholm and Tegner scores are valid as patient-administered scores and responsive at early time points after treatment of anterior cruciate ligament tears.Study Design: Cohort study (Diagnosis); Level of evidence, 1. Methods: All patients were treated for an anterior cruciate ligament tear. For responsiveness, the Lysholm score (n = 1075) and Tegner activity level (n = 505) were measured preoperatively and 6, 9, 12, and 24 months postoperatively. For test-retest (n = 50), scores were measured at 2 years postoperatively and again within 4 weeks by questionnaire. For criterion validity (n = 170), patients completed the Short Form-12 and the International Knee Documentation Committee score in addition to Lysholm and Tegner instruments. For all other analyses, preoperative Lysholm score (n = 1783) or Tegner activity levels (n = 687) were collected.Results: There was acceptable test-retest reliability for both the Lysholm (intraclass correlation coefficient = 0.9) and Tegner (intraclass correlation coefficient = 0.8) scores. The minimum detectable change for Lysholm was 8.9 and for Tegner was 1. The Lysholm demonstrated acceptable internal consistency. The Lysholm correlated with the International Knee Documentation Committee (r = .8) and the Short Form-12 (r = .4), and Tegner correlated with the Short Form-12 (r = .2). Both scores had acceptable floor and ceiling effects and all hypotheses were significant. The Lysholm and Tegner were responsive to change at each of the time points.Conclusion: After 25 years of changes in treatment of anterior cruciate ligament injuries, the Lysholm knee score and the Tegner activity scale demonstrated acceptable psychometric parameters as patient-administered scores and showed acceptable responsiveness to be used in early return to function after anterior cruciate ligament treatment.
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- Huyghe, Jeroen R., et al.
(författare)
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Genome-wide SNP analysis reveals no gain in power for association studies of common variants in the Finnish Saami
- 2010
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Ingår i: European Journal of Human Genetics. - : Nature Publishing Group. - 1018-4813 .- 1476-5438. ; 18:5, s. 569-574
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Tidskriftsartikel (refereegranskat)abstract
- The Saami from Fennoscandia are believed to represent an ancient, genetically isolated population with no evidence of population expansion. Theoretical work has indicated that under this demographic scenario, extensive linkage disequilibrium (LD) is generated by genetic drift. Therefore, it has been suggested that the Saami would be particularly suited for genetic association studies, offering a substantial power advantage and allowing more economic study designs. However, no study has yet assessed this claim. As part of a GWAS for a complex trait, we evaluated the relative power for association studies of common variants in the Finnish Saami. LD patterns in the Saami were very similar to those in the non-African HapMap reference panels. Haplotype diversity was reduced and, on average, levels of LD were higher in the Saami as compared with those in the HapMap panels. However, using a 'hidden' SNP approach we show that this does not translate into a power gain in association studies. Contrary to earlier claims, we show that for a given set of common SNPs, genomic coverage attained in the Saami is similar to that in the non-African HapMap panels. Nevertheless, the reduced haplotype diversity could potentially facilitate gene identification, especially if multiple rare variants play a role in disease etiology. Our results further indicate that the HapMap is a useful resource for genetic studies in the Saami.
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- Van Laer, Lut, et al.
(författare)
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A genome-wide association study for age-related hearing impairment in the Saami
- 2010
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Ingår i: European Journal of Human Genetics. - : BMJ Publishing Group Ltd. - 1018-4813 .- 1476-5438. ; 18:6, s. 685-693
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Tidskriftsartikel (refereegranskat)abstract
- This study aimed at contributing to the elucidation of the genetic basis of age-related hearing impairment (ARHI), a common multifactorial disease with an important genetic contribution as demonstrated by heritability studies. We conducted a genome-wide association study (GWAS) in the Finnish Saami, a small, ancient, genetically isolated population without evidence of demographic expansion. The choice of this study population was motivated by its anticipated higher extent of LD, potentially offering a substantial power advantage for association mapping. DNA samples and audiometric measurements were collected from 352 Finnish Saami individuals, aged between 50 and 75 years. To reduce the burden of multiple testing, we applied principal component (PC) analysis to the multivariate audiometric phenotype. The first three PCs captured 80% of the variation in hearing thresholds, while maintaining biologically important audiometric features. All subjects were genotyped with the Affymetrix 100 K chip. To account for multiple levels of relatedness among subjects, as well as for population stratification, association testing was performed using a mixed model. We summarised the top-ranking association signals for the three traits under study. The top-ranked SNP, rs457717 (P-value 3.55 x 10(-7)), was associated with PC3 and was localised in an intron of the IQ motif-containing GTPase-activating-like protein (IQGAP2). Intriguingly, the SNP rs161927 (P-value 0.000149), seventh-ranked for PC1, was positioned immediately downstream from the metabotropic glutamate receptor-7 gene (GRM7). As a previous GWAS of a European and Finnish sample set already suggested a role for GRM7 in ARHI, this study provides further evidence for the involvement of this gene.
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- Weitoft, Tomas, et al.
(författare)
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Pentraxin 3 in serum and synovial fluid of patients with rheumatoid arthritis with and without autoantibodies
- 2017
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Ingår i: Scandinavian Journal of Rheumatology. - : Informa UK Limited. - 0300-9742 .- 1502-7732. ; 46:5, s. 346-352
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES:Pentraxin 3 (PTX3) is a locally produced multifunctional protein involved in inflammation, matrix deposition, and immunity. As patients with seropositive rheumatoid arthritis (RA) have a more severe disease course and higher risk of joint destruction than seronegative patients, the aim of the present study was to examine differences in PTX3 in synovial fluid (SF) (and serum) in seropositive compared to seronegative RA, and other local markers of inflammation and destruction.METHOD:Ninety-seven RA patients with knee effusion were included. Serum and SF levels of PTX3, as well as serum levels of anti-citrullinated protein antibody and rheumatoid factor of immunoglobulin A and M subclasses, and markers of inflammation and potential destruction in SF: white blood cell counts, tumour necrosis factor, interleukin-6, vascular endothelial growth factor, metalloproteinase 3, and cartilage oligomeric matrix protein, were analysed. In addition, a radiographic knee examination was performed.RESULTS:Seropositive patients had significantly higher PTX3 levels in SF than seronegative patients, whereas there was no difference for serum levels. SF-PTX3 levels correlated with disease activity and with local inflammatory markers, especially polymorphonuclear cells, and with autoantibody levels. There was no correlation between PTX3 levels in serum and SF.CONCLUSION:The correlation of disease activity and autoantibody levels with SF-PTX3 levels in antibody-positive patients suggests a role for PTX3 in the inflammatory process specifically in seropositive RA joints, and supports the hypothesis that seropositive and seronegative RA are different disease entities. Polymorphonuclear granulocytes may be an important source of PTX3 in RA SF.
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