| 1. |
- Abelson, Anna-Karin, et al.
(författare)
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STAT4 Associates with SLE through two independent effects that correlate with gene expression and act additively with IRF5 to increase risk
- 2009
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Ingår i: Annals of the Rheumatic Diseases. - : BMJ. - 0003-4967 .- 1468-2060. ; 68:11, s. 1746-1753
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: To confirm and define the genetic association of STAT4 and systemic lupus erythematosus, investigate the possibility of correlations with differential splicing and/or expression levels, and genetic interaction with IRF5. METHODS: 30 tag SNPs were genotyped in an independent set of Spanish cases and controls. SNPs surviving correction for multiple tests were genotyped in 5 new sets of cases and controls for replication. STAT4 cDNA was analyzed by 5'-RACE PCR and sequencing. Expression levels were measured by quantitative PCR. RESULTS: In the fine-mapping, four SNPs were significant after correction for multiple testing, with rs3821236 and rs3024866 as the strongest signals, followed by the previously associated rs7574865, and by rs1467199. Association was replicated in all cohorts. After conditional regression analyses, two major independent signals represented by SNPs rs3821236 and rs7574865, remained significant across the sets. These SNPs belong to separate haplotype blocks. High levels of STAT4 expression correlated with SNPs rs3821236, rs3024866 (both in the same haplotype block) and rs7574865 but not with other SNPs. We also detected transcription of alternative tissue-specific exons 1, indicating presence of tissue-specific promoters of potential importance in the expression of STAT4. No interaction with associated SNPs of IRF5 was observed using regression analysis. CONCLUSIONS: These data confirm STAT4 as a susceptibility gene for SLE and suggest the presence of at least two functional variants affecting levels of STAT4. Our results also indicate that both genes STAT4 and IRF5 act additively to increase risk for SLE.
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| 2. |
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| 3. |
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| 4. |
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| 5. |
- Andersson, M. L. E., et al.
(författare)
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Diurnal variation in serum levels of cartilage oligomeric matrix protein in patients with knee osteoarthritis or rheumatoid arthritis
- 2006
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Ingår i: Annals of the Rheumatic Diseases. - : BMJ. - 0003-4967 .- 1468-2060. ; 65:11, s. 1490-1494
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To monitor changes in serum concentrations of cartilage oligomeric matrix protein (COMP) during a 24-h period to determine any diurnal variation, and to estimate the half life of COMP in the circulation in patients with symptomatic knee osteoarthritis and in those with rheumatoid arthritis. Methods: Serum samples were drawn every 4 h (7 samples/patient over 24 h) in 10 patients with knee osteoarthritis and 14 patients with rheumatoid arthritis. Osteoarthritis was defined radiographically and clinically (American College of Rheumatology (ACR) criteria) and rheumatoid arthritis according to the 1987 ACR criteria. Serum COMP was measured by sandwich ELISA. A statistical model for the diurnal variation in the COMP levels was developed using the computer program NONMEM. Results: No considerable changes in COMP levels were observed during the day between 08:00 and 21:00 in either group. A significant decrease in serum COMP was apparent during bed rest at night, reaching the lowest levels between 04:00 and 05:00 (p < 0.03 or better v all other time points) in patients with osteoarthritis and in those with rheumatoid arthritis. From the rate of decreasing serum COMP levels, a putative half life of COMP in the circulation was estimated to be 7.4 h. Conclusion: During normal daytime activities, serum COMP levels are constant. The decrease during the night indicates a rapid elimination of COMP once it has reached the circulation. The stable COMP levels during the day suggest that it is not necessary to further standardise the time of serum sampling in clinical practice.
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| 6. |
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| 7. |
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| 8. |
- Arvidsson, Susann, 1965-, et al.
(författare)
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Chronic musculoskeletal pain and sleep disturbances as predictors for lower vitality measured by the short form 36 (SF-36) - A eight-year follow up study
- 2006
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Ingår i: Annals of the Rheumatic Diseases. - London : BMJ Books. - 0003-4967 .- 1468-2060. ; 65:Suppl. 2, s. 656-656
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Background: Subjects with chronic musculoskeletal pain or sleep disturbances have been shown to have a poor healthstatus as measured by the SF-36 health survey. Fatigue is commonly reported by subjects with chronic musculoskeletal pain and sleep disturbances. There is little known about the temporal relationship between chronic pain, sleep disturbances and changes of vitality.Objectives: The aim of this study was to evaluate the predictive value of chronic musculoskeletal pain and sleep disturbances with regard to changes in vitality as measured by SF-36 over an eight year period.Method: An eight year follow up of 2 425 subjects aged 20-74 from the general population that in 1995 answered the same postal questionnaire. The questionnaire assessed chronic musculoskeletal pain, sleep disturbances, and included the SF-36 health survey. Pain was considered "chronic" if persistent for three months or more. Sleep disturbances assessed were difficulty in falling asleep, frequent awakenings, early awakenings and not feeling rested. Main outcome measure was change of vitality as measured by SF-36 in those that at baseline reported vitality over the median value. Statistical analyses were done with use of logistic regression. Besides the studied variables, the logistic regression analyses also controlled for gender, age, socio-economic group, and the use of analgesics and sleeping pills.Results: At baseline 1212 subjects reported a vitality score on SF-36 above the median score of 75. There were 943 subjects (78%) responding at the eight-year follow up. Chronic pain at baseline predicted (OR=1,64, 95% CI 1,14-2,36%, p=0,01) worsening of vitality over time. Loss of vitality was also predicted by moderate problems with falling asleep (OR=2,17, 95% CI 1,31-3,60%, p<0,01), and problems with not feeling rested (moderate problems OR=2,08, 95% CI 1,23-3,50%, p=0,01, and major problems OR=4,76, 95% CI 1,53-14,78%, p=0,01).Conclusion: Loss of vitality in SF-36 over an eight-year period was predicted by chronic musculoskeletal pain, problems with falling asleep and problems with not feeling rested. Problems with frequent awakenings and early awakenings did not predict lower value of vitality over an eight-year period. It could thus be important to attend to sleeping problems and especially the feeling of not being rested in subjects with chronic musculoskeletal pain.
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| 9. |
- Arvidsson, Susann, 1965-, et al.
(författare)
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Feeling rested predicts good health in subjects with and without chronic musculoskeletal pain
- 2008
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Ingår i: Annals of the Rheumatic Diseases. - London : BMJ Books. - 0003-4967 .- 1468-2060. ; 67:Suppl. II, s. 552-552
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Tidskriftsartikel (refereegranskat)abstract
- Background: Musculoskeletal pain is a public health problem and a common cause for people to seek health care. It has also been shown that people with musculoskeletal pain estimates their health-related quality of life very low compared to a pain free population. Earlier studies have primarily looked at risk factors and there are little known about health predicting factors in a general population.Objectives: To investigate the associations between suggested health factors and health-related quality of life at baseline and in an eight-year follow up in subjects with and without chronic musculoskeletal pain.Methods: A longitudinal study in a Swedish general population (N=1 849) with a postal questionnaire at baseline 1995 and at a follow up 2003. Subjects were divided into two groups, according to their response about chronic musculoskeletal pain at baseline. Health-related quality of life was assessed by the SF-36 together with suggested health factors. The associations between the dependent variables (SF-36 subscales) and the independent variables (i.e. the suggested health factors; socioeconomic status, immigrant status, emotional support, regularly exercise, sleep structure, feeling rested, smoking and alcohol habits) were estimated by OR and 95% CI calculated by multivariable logistic regressions, with adjustment for all health factors, age, sex and baseline SF-36 values.Results: The most consistent finding for subjects with and without chronic musculoskeletal pain at baseline and in the eight-year follow up was a statistical significant (p<0.05) better health outcome in SF-36 subscales for subjects that were feeling rested at baseline. At baseline feeling rested was associated with having a health status better than the mean score in seven SF-36 subscales for both subjects with chronic pain (OR 1.5 (95% CI 1.0-2.3) – OR 4.4 (95% CI 2.9-6.6)) and subjects without chronic pain (OR 2.6 (95% CI 1.6-4.1) – OR 4.4 (95% CI 3.0-6.5)). At the follow up feeling rested predicted a better outcome in five subscales for subjects with chronic pain (OR 1.6 (95% CI 1.0-2.4) – OR 2.2 (95% CI 1.4-3.6)) and in six subscales for subjects without chronic pain (OR 1.6 (95% CI 1.0-2.5) – OR 2.7 (95% CI 1.8-4.1)). Other factors that in some aspects predicted a better outcome were belonging to higher socioeconomic group, being an inborn Swede, having emotional support, having good sleep structure, never being or being a former smoker, and regularly drinking alcohol.Conclusion: ''Feeling rested'' was the most consistent factor predicting a good health outcome, both in subjects with and without chronic musculoskeletal pain, and should be attended to in health promotion work. Emotional support, sleep structure, smoking and alcoholic habits also appears to be important health factors to take into account.
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| 10. |
- Arvidsson, Susann, 1965-, et al.
(författare)
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In Patient Team Care Improved Health-Related Quality of Life for Patients with Rheumatic Diseases over Three and Six Months
- 2006
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Ingår i: Annals of the Rheumatic Diseases. - London : BMJ Books. - 0003-4967 .- 1468-2060. ; 65:Suppl. 2, s. 274-275
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Tidskriftsartikel (refereegranskat)abstract
- Background: For measuring outcomes in team care, different aspects in the ICF (International Classification of Functioning) are relevant. Health-related quality of life as measured by SF-36 includes aspects of body function as well as activity and participation. HADS (Hospital Anxiety and Depression Scale) reflects more personal factors. Individuals with rheumatic diseases experience lower degree of health-related quality of life, compared with the general population.Objectives: To examine health-related quality of life as well as anxiety and depression in patients with rheumatic diseases directly after and three and six months after a period of three weeks in patient team based multiprofessional rehabilitation at a unit specialised for patients with different rheumatic diseases.Method: Quasi-experimental design with pre- and post-test in consecutive adult patients (Rheumatoid arthritis n=23, Spondylarthritides n=14, Osteoarthritis n=6, Other inflammatory rheumatic diseases n=10), one week before(n=55), one week after(n=53), three (n=40) and six months (n=36) after a period of three weeks of in patient team based multiprofessional care at a unit for rheumatic diseases. The instruments used for outcome measurements were the Short Form 36 Health questionnaire (SF-36) and the Hospital Anxiety and Depression Scale (HADS). Statistical analysis was done with the SPSS package 13.0. Differences between groups were evaluated with Wilcoxon signed rank test.Results: The patients reported worse outcome on the eight health scales in SF-36, at baseline and one week, three and six months after the rehabilitation, when comparing with the norm for the Swedish population. The mean values for SF-36 improved in all eight subscales one week after the rehabilitation period and six of the health scales obtained statistically significant improvement (p<0.05). Three and six months later there was still a statistically (p<0.05 for 3/8 subscales; Role Physical (RP), Vitality(VT) and Mental Health(MH)) and/or clinically significant (5/8 subscales; Physical function(PF), Bodily Pain(BP), General Health(GH), Social Fundtioning(SF) and Role Emotional(RE)) improvement as compared to the levels before the rehabilitation period. The levels for anxiety and depression as measured by HADS improved significantly (p<0.05) one week after the rehabilitation period as compared to baseline. Three and six months after the rehabilitation period, the levels were the same as at baseline.Conclusion: Earlier studies and this study have shown that people with rheumatic diseases experience reduced health-related quality of life and increased anxiety and depression. The result from this study showed that after a period of three weeks in patient team based multiprofessional rehabilitation, the experience of health-related quality of life was improved also after three and six months whereas the improvement in anxiety and depression returned to baseline after three and six months. Thus, improvements in health-related quality of life seem to reflect other aspects of the disease consquences than anxiety and depression.
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| 11. |
- Askling, Johan, et al.
(författare)
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Anti-TNF therapy in RA and risk of malignant lymphomas Relative risks and time-trends in the Swedish Biologics Register
- 2008
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Ingår i: Annals of the Rheumatic Diseases. - : BMJ Publishing Group Ltd. - 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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| 12. |
- 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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| 13. |
- Askling, J, et al.
(författare)
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Do steroids increase lymphoma risk? A case-control study of lymphoma risk in polymyalgia rheumatica/giant cell arteritis
- 2005
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Ingår i: Annals of the Rheumatic Diseases. - : BMJ. - 0003-4967 .- 1468-2060. ; 64:12, s. 1765-1768
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND:Recent studies indicate increased risks of malignant lymphomas among individuals treated with corticosteroids, but have not taken into account the underlying reasons for steroid use, so the increased risks might be attributable to the underlying disease or concomitant treatments other than steroids. Polymyalgia rheumatica (PMR) and temporal arteritis (giant cell arteritis, GCA) are common inflammatory conditions treated with steroids as single immunosuppressive therapy, but data on lymphoma risk in GCA/PMR are limited.OBJECTIVE:To assess the risk of lymphoma associated with steroid treatment of GCA/PMR.METHODS:The association between GCA/PMR and malignant lymphomas (overall, and separately for non-Hodgkin lymphoma, Hodgkin lymphoma, and chronic lymphatic leukaemia) was examined in a nationwide, population based, case-control study of 42,676 lymphoma cases and 78,487 matched population controls, using prospectively recorded data on lymphomas from the Swedish cancer register 1964-2000 and data on pre-lymphoma hospital admissions for GCA/PMR from the Swedish inpatient register 1964-2000. Odds ratios (OR) associated with a pre-lymphoma hospital admission for GCA/PMR were calculated using conditional logistic regression.RESULTS:153 lymphoma cases and 345 population controls had a history of GCA/PMR, resulting in an overall OR for malignant lymphomas of 0.81 (95% confidence interval, 0.67 to 0.98). The OR varied little with lymphoma type, sex, age, and calendar period. The OR for GCA was 0.67 (0.48 to 0.98) and for PMR, 0.83 (0.67 to 1.04).CONCLUSIONS:Treated GCA is not associated with increased lymphoma risks, which suggests that even at considerable cumulative doses, steroids may not appreciably increase lymphoma risk.
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| 14. |
- 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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| 15. |
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| 16. |
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| 17. |
- 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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| 18. |
- Askling, J, et al.
(författare)
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Swedish registers to examine drug safety and clinical issues in RA
- 2006
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Ingår i: Annals of the Rheumatic Diseases. - : BMJ. - 1468-2060 .- 0003-4967. ; 65:6, s. 707-712
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Forskningsöversikt (refereegranskat)abstract
- Data from several different monitoring systems are examined. The potential for registers based on data obtained from clinical practice, and linkage of such data to national health and population registers, is discussed. The approach described is a possible prototype for long term surveillance systems needed for the safe introduction of new treatments.
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| 19. |
- Askling, Johan, et al.
(författare)
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Time-dependent increase in risk of hospitalisation with infection among Swedish RA patients treated with TNF antagonists
- 2007
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Ingår i: Annals of the Rheumatic Diseases. - : BMJ. - 0003-4967 .- 1468-2060. ; 66:10, s. 1339-1344
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES:The degree to which treatment with tumour necrosis factor (TNF) antagonists may be associated with increased risks for serious infections is unclear. An observational cohort study was performed using prospectively collected data from the Swedish Biologics Register (ARTIS) and other national Swedish registers.METHODS:First, in the ARTIS, all 4167 rheumatoid arthritis (RA) patients starting TNF antagonist treatment between 1999 and 2003 were identified. Secondly, in the Swedish Inpatient Register, all individuals hospitalised for any reason and who also carried a diagnosis of RA, between 1964 and 2003 (n = 44 946 of whom 2692 also occurred in ARTIS), were identified. Thirdly, in the Swedish Inpatient Register, all hospitalisations listing an infection between 1999 and 2003 were identified. By cross-referencing these three data sets, RRs for hospitalisation with infection associated with TNF antagonist treatment were calculated within the cohort of 44 946 RA patients, using Cox regression taking sex, age, geography, co-morbidity and use of inpatient care into account.RESULTS:Among the 4167 patients treated with TNF antagonists, 367 hospitalisations with infections occurred during 7776 person-years. Within the cohort of 44 496 RA patients, the RR for infection associated with TNF antagonists was 1.43 (95% CI 1.18 to 1.73) during the first year of treatment, 1.15 (95% CI 0.88 to 1.51) during the second year of treatment, and 0.82 (95% CI 0.62 to 1.08) for subjects remaining on their first TNF antagonist treatment after 2 years.CONCLUSION:Treatment with TNF antagonists may be associated with a small to moderate increase in risk of hospitalisation with infection, which disappears with increasing treatment duration.
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| 20. |
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| 21. |
- Berglin, Ewa, MD, PhD, 1955-, et al.
(författare)
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Radiological outcome in rheumatoid arthritis is predicted by presence of antibodies against cyclic citrullinated peptide before and at disease onset, and by IgA-RF at disease onset
- 2006
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Ingår i: Annals of the Rheumatic Diseases. - : BMJ Publishing Group Ltd. - 0003-4967 .- 1468-2060. ; 65:4, s. 453-458
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: To evaluate the significance of antibodies against cyclic citrullinated peptide (anti-CCP) and rheumatoid factors (RFs), before the onset of rheumatoid arthritis and when presenting as early disease (baseline), for disease activity and progression. METHODS: 93 of a cohort of 138 patients with early rheumatoid arthritis (<12 months of symptoms) had donated blood before symptoms of rheumatoid arthritis (defined as pre-patients) and were identified from among blood donors within the Medical Biobank of northern Sweden. Disease activity (erythrocyte sedimentation rate (ESR), C reactive protein, joint score, global visual analogue scale) and radiological destruction in hands and feet (Larsen score) were assessed at baseline and after two years. Anti-CCP antibodies and RFs were analysed using enzyme immunoassays. HLA shared epitope (SE) alleles (DRB1*0401/0404) were identified. RESULTS: Patients with anti-CCP antibodies before disease onset had significantly higher Larsen score at baseline and after two years. In multiple regression analyses baseline values of anti-CCP/IgA-RF/IgG-RF/IgM-RF, swollen joint count, and Larsen score significantly predicted radiological outcome at two years. In logistic regression analyses, baseline values of anti-CCP antibodies/IgA-RF, therapeutic response at six months, and swollen joint count/ESR significantly predicted radiological progression after two years. The baseline titre of anti-CCP antibodies was higher in patients with radiological progression and decreased significantly in those with response to therapy. SE allele carriage was associated with a positive test for anti-CCP antibodies in pre-patients and in early rheumatoid arthritis. CONCLUSIONS: Presence of anti-CCP antibodies before disease onset is associated with more severe radiological damage. The titre of anti-CCP antibodies is related to disease severity.
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| 22. |
- Bernatsky, S, et al.
(författare)
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Non-Hodgkin's lymphoma in systemic lupus erythematosus
- 2005
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Ingår i: Annals of the Rheumatic Diseases. - : BMJ. - 1468-2060 .- 0003-4967. ; 64:10, s. 1507-1509
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Tidskriftsartikel (refereegranskat)abstract
- Background: Recent evidence supports an association between systemic lupus erythematosus (SLE) and non-Hodgkin's lymphoma (NHL). Objectives: To describe demographic factors, subtypes, and survival of patients with SLE who develop NHL. Methods: A multi-site cohort of 9547 subjects with definite SLE was assembled. Subjects at each centre were linked to regional tumour registries to determine cancer cases occurring after SLE diagnosis. For the NHL cases ascertained, descriptive statistics were calculated, and NHL subtype frequency and median survival time of patients determined. Results: 42 cases of NHL occurred in the patients with SLE during the 76 948 patient-years of observation. The median age of patients at NHL diagnosis was 57 years. Thirty six (86%) of the 42 patients developing NHL were women, reflecting the female predominance of the cohort. In the patients, aggressive histological subtypes appeared to predominate, with the most commonly identified NHL subtype being diffuse large B cell ( 11 out of 21 cases for which histological subtype was available). Twenty two of the patients had died a median of 1.2 years after lymphoma diagnosis. Conclusions: These data suggest aggressive disease in patients with SLE who develop NHL. Continuing work should provide further insight into the patterns of presentation, prognosis, and aetiology of NHL in SLE.
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| 23. |
- Bertsias, G., et al.
(författare)
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EULAR recommendations for the management of systemic lupus erythematosus. Report of a task force of the EULAR standing committee for international clinical studies including therapeutics
- 2008
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Ingår i: Annals of the Rheumatic Diseases. - : BMJ. - 1468-2060 .- 0003-4967. ; 67:2, s. 195-205
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Forskningsöversikt (refereegranskat)abstract
- Objective: Systemic lupus erythematosus (SLE) is a complex disease with variable presentations, course and prognosis. We sought to develop evidence-based recommendations addressing the major issues in the management of SLE. Methods: The EULAR Task Force on SLE comprised 19 specialists and a clinical epidemiologist. Key questions for the management of SLE were compiled using the Delphi technique. A systematic search of PubMed and Cochrane Library Reports was performed using McMaster/Hedges clinical queries' strategies for questions related to the diagnosis, prognosis, monitoring and treatment of SLE. For neuropsychiatric, pregnancy and antiphospholipid syndrome questions, the search was conducted using an array of relevant terms. Evidence was categorised based on sample size and type of design, and the categories of available evidence were identified for each recommendation. The strength of recommendation was assessed based on the category of available evidence, and agreement on the statements was measured across the 19 specialists. Results: Twelve questions were generated regarding the prognosis, diagnosis, monitoring and treatment of SLE, including neuropsychiatric SLE, pregnancy, the antiphospholipid syndrome and lupus nephritis. The evidence to support each proposition was evaluated and scored. After discussion and votes, the final recommendations were presented using brief statements. The average agreement among experts was 8.8 out of 10. Conclusion: Recommendations for the management of SLE were developed using an evidence-based approach followed by expert consensus with high level of agreement among the experts.
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| 24. |
- Bertsias, G. K., et al.
(författare)
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EULAR points to consider for conducting clinical trials in systemic lupus erythematosus: literature based evidence for the selection of endpoints
- 2009
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Ingår i: Annals of the Rheumatic Diseases. - : BMJ. - 1468-2060 .- 0003-4967. ; 68:4, s. 477-483
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Forskningsöversikt (refereegranskat)abstract
- Objective: To assess available evidence on the use of end-points ( outcome measures) in clinical trials in systemic lupus erythematosus (SLE), as a part of the development of evidence-based recommendations for points to consider in clinical trials in SLE. Methods: The European League Against Rheumatism (EULAR) Task Force on SLE comprised 19 specialists, a clinical epidemiologist and a research fellow. Key questions addressing the evidence for clinical trial end-points in SLE were compiled using the Delphi technique. A systematic search of the PubMed and Cochrane Library databases was performed using McMaster/Hedges clinical query strategies and an array of relevant terms. Evidence was categorised based on sample size and type of design, and the categories of available evidence were identified for each recommendation. The strength of recommendation was assessed based on the category of available evidence and agreement on the statements was measured across the 19 specialists. Results: Eight questions were generated regarding end-points for clinical trials. The evidence to support each proposition was evaluated. The literature review revealed that most outcome measures used in phase 2/3 trials in SLE have not been formally validated in clinical trials, although some indirect validation has been undertaken. Conclusion: This systematic literature review forms the evidence base considered in the development of the EULAR recommendations for end-points in clinical trials in SLE.
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| 25. |
- Blom, Anna, et al.
(författare)
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C4b-binding protein (C4BP) inhibits development of experimental arthritis in mice
- 2009
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Ingår i: Annals of the Rheumatic Diseases. - London : BMJ Publishing Group Ltd. - 0003-4967 .- 1468-2060. ; 68:1, s. 136-142
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: To assess the human complement inhibitor C4b-binding protein (C4BP) for treatment of arthritis. METHODS: We have used two mouse models of rheumatoid arthritis (RA) to assess the therapeutic effect of C4BP on different phases of arthritis, the collagen antibody-induced arthritis (CAIA), an acute antibody-induced disease and the collagen-induced arthritis (CIA), which carries the full complexity of arthritis. RESULTS: Purified human C4BP injected intraperitoneally alleviated CAIA significantly in a manner similar to cobra venom factor that depletes complement due to massive activation. Furthermore, C4BP was injected before and after the disease development into CIA mice. In the former case, the disease onset was delayed and in the latter, the severity of the disease was reduced in animals treated with C4BP. However, C4BP did not affect the anti-CII antibody synthesis. C4BP present in mouse sera decreased activity of the classical but not the alternative pathway of the complement system when these were assessed in a fluid phase. However, C4BP was efficiently inhibiting the alternative pathway when present on the activating surface. Taken together, the disease ameliorating effect of C4BP appears to be related to inhibition of both pathways of complement. CONCLUSIONS: Although human C4BP was cleared relatively fast from the circulation and was only moderately affecting complement activity, its effect on the disease severity was substantial, suggesting that minor alterations in complement activity can have significant therapeutic value in RA.
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