| 1. |
|
|
| 2. |
|
|
| 3. |
- Askling, Johan, et al.
(författare)
-
Anti-TNF therapy in RA and risk of malignant lymphomas Relative risks and time-trends in the Swedish Biologics Register
- 2008
-
Ingår i: Annals of the Rheumatic Diseases. - : BMJ Publishing Group Ltd. - 0003-4967 .- 1468-2060. ; 68:5, s. 648-653
-
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.
|
|
| 4. |
- Askling, Johan, et al.
(författare)
-
Cancer risk in patients with rheumatoid arthritis treated with anti-tumor necrosis factor alpha therapies : does the risk change with the time since start of treatment?
- 2009
-
Ingår i: Arthritis and Rheumatism. - : Wiley. - 0004-3591 .- 1529-0131. ; 60:11, s. 3180-3189
-
Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE:To determine the short-term and medium-term risks of cancer in patients receiving anti-tumor necrosis factor alpha (anti-TNFalpha) therapies that have proven effective in the treatment of chronic inflammatory conditions.METHODS:By linking together data from the Swedish Biologics Register, Swedish registers of RA, and the Swedish Cancer Register, we identified and analyzed for cancer occurrence a national cohort of 6,366 patients with RA who first started anti-TNF therapy between January 1999 and July 2006. As comparators, we used a national biologics-naive RA cohort (n = 61,160), a cohort of RA patients newly starting methotrexate (n = 5,989), a cohort of RA patients newly starting disease-modifying antirheumatic drug combination therapy (n = 1,838), and the general population of Sweden. Relative risks (RRs) were estimated using Cox regression analyses, examining overall RR as well as RR by time since the first start of anti-TNF therapy, by the duration of active anti-TNF therapy, and by the anti-TNF agent received.RESULTS:During 25,693 person-years of followup in 6,366 patients newly starting anti-TNF, 240 first cancers occurred, yielding an RR of 1.00 (95% confidence interval 0.86-1.15) versus the biologics-naive RA cohort, and similar RRs versus the other 2 RA comparators. RRs did not increase with increasing time since the start of anti-TNF therapy, nor with the cumulative duration of active anti-TNF therapy. During the first year following the first treatment start, but not thereafter, dissimilar cancer risks for adalimumab, etanercept, and infliximab were observed.CONCLUSION:During the first 6 years after the start of anti-TNF therapy in routine care, no overall elevation of cancer risk and no increase with followup time were observed.
|
|
| 5. |
- Askling, Johan, et al.
(författare)
-
Risk and case characteristics of tuberculosis in rheumatoid arthritis associated with tumor necrosis factor antagonists in Sweden
- 2005
-
Ingår i: Arthritis and Rheumatism. - : Wiley. - 0004-3591 .- 1529-0131. ; 52:7, s. 1986-1992
-
Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE:Because treatment with tumor necrosis factor (TNF) antagonists may increase the risk of tuberculosis (TB), and because knowledge of the risk of TB in rheumatoid arthritis (RA) not treated with biologics is scarce and of uncertain generalizability to low-risk populations, this study sought to determine the risk of TB among Swedish patients with RA.METHODS:Using data from Swedish nationwide and population-based registers and data from an ongoing monitoring program of TNF antagonists, the relative risks of TB in patients with RA (versus the general population) and of TB associated with TNF antagonists (versus RA patients not treated with biologics) were determined by comparing the incidence of hospitalization for TB in 3 RA cohorts and 2 general population cohorts from 1999 to 2001. We also reviewed the characteristics of all reported cases of TB in RA patients treated with TNF antagonists in Sweden and calculated the incidence of TB per type of TNF antagonist between 1999 and 2004.RESULTS:During 1999-2001, RA patients who were not treated with TNF antagonists were at increased risk of TB versus the general population (relative risk 2.0, 95% confidence interval [95% CI] 1.2-3.4). RA patients treated with TNF antagonists had a 4-fold increased risk of TB (relative risk 4.0, 95% CI 1.3-12) versus RA patients not treated with TNF antagonists. The reported TB cases during 1999-2004 in RA patients exposed to TNF antagonists (9 infliximab, 4 etanercept, 2 both) were predominantly pulmonary. TB occurred up to 3 years following the start of treatment.CONCLUSION:Irrespective of whether TNF antagonists are administered, Swedish patients with RA are at increased risk of TB. During 1999-2001, TNF antagonists were associated with an increased risk of TB, up to 4-fold in magnitude. This increased risk may persist over time during treatment and is related to both infliximab and etanercept.
|
|
| 6. |
- Askling, Johan, et al.
(författare)
-
Time-dependent increase in risk of hospitalisation with infection among Swedish RA patients treated with TNF antagonists
- 2007
-
Ingår i: Annals of the Rheumatic Diseases. - : BMJ. - 0003-4967 .- 1468-2060. ; 66:10, s. 1339-1344
-
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.
|
|
| 7. |
- Baecklund, Eva, et al.
(författare)
-
Association of chronic inflammation, not its treatment, with increased lymphoma risk in rheumatoid arthritis
- 2006
-
Ingår i: Arthritis and Rheumatism. - : Wiley. - 0004-3591 .- 1529-0131. ; 54:3, s. 692-701
-
Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE:Chronic inflammatory conditions such as rheumatoid arthritis (RA) have been associated with malignant lymphomas. This study was undertaken to investigate which patients are at highest risk, and whether antirheumatic treatment is hazardous or protective.METHODS:We performed a matched case-control study of 378 consecutive Swedish RA patients in whom malignant lymphoma occurred between 1964 and 1995 (from a population-based RA cohort of 74,651 RA patients), and 378 controls. Information on disease characteristics and treatment from onset of RA until lymphoma diagnosis was abstracted from medical records. Lymphoma specimens were reclassified and tested for Epstein-Barr virus (EBV). Relative risks (odds ratios [ORs]) for lymphomas (by subtype) associated with deciles of cumulative disease activity were assessed, as were ORs associated with drug treatments.RESULTS:The relative risks of lymphoma were only modestly elevated up to the seventh decile of cumulative disease activity. Thereafter, the relative risk increased dramatically (OR ninth decile 9.4 [95% confidence interval 3.1-28.0], OR tenth decile 61.6 [95% confidence interval 21.0-181.0]). Most lymphomas (48%) were of the diffuse large B cell type, but other lymphoma subtypes also displayed an association with cumulative disease activity. Standard nonbiologic treatments did not increase lymphoma risk. EBV was present in 12% of lymphomas.CONCLUSION:Risk of lymphoma is substantially increased in a subset of patients with RA, those with very severe disease. High inflammatory activity, rather than its treatment, is a major risk determinant.
|
|
| 8. |
- Baecklund, Eva, et al.
(författare)
-
Characteristics of diffuse large B cell lymphomas in rheumatoid arthritis
- 2006
-
Ingår i: Arthritis and Rheumatism. - : Wiley. - 0004-3591 .- 1529-0131. ; 54:12, s. 3774-3781
-
Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE:Patients with rheumatoid arthritis (RA) are at increased risk of malignant lymphomas, with a correlation between RA disease severity and lymphoma risk, most pronounced for diffuse large B cell lymphomas (DLBCLs), which also constitute the majority of RA-associated lymphomas. DLBCLs can be further subdivided into germinal center (GC)-like and non-GC-like subtypes, with different cellular origins and prognoses. This study was undertaken to investigate whether RA displays a specific association with any of the DLBCL subtypes.METHODS:We identified 139 patients with DLBCLs within a population-based case-control study of 378 RA patients with lymphoma. The DLBCLs were examined for CD10, Bcl-6, and interferon regulatory factor 4 expression patterns, subclassified into GC and non-GC subtypes, and then correlated with clinical parameters.RESULTS:We found a statistically significant predominance of the non-GC subtype (97 patients; 70% of all DLBCLs). These patients more often had an advanced stage of lymphoma at diagnosis and had a worse 5-year overall survival rate (16% versus 33%) compared with patients with the GC subtype. There was a strong association with RA disease activity in both subtypes, with >70% of the GC and non-GC cases occurring in RA patients with the highest overall disease activity scores.CONCLUSION: These findings suggest that severe RA is particularly associated with the non-GC subtype of DLBCL, and indicate a critical role of activated peripheral B cells as the cells of origin in these lymphomas.
|
|
| 9. |
|
|
| 10. |
|
|
| 11. |
- Baecklund, Eva, et al.
(författare)
-
Expression of the human germinal-centre-associated lymphoma protein in diffuse large B-cell lymphomas in patients with rheumatoid arthritis
- 2008
-
Ingår i: British Journal of Haematology. - : Wiley. - 0007-1048 .- 1365-2141. ; 141:1, s. 69-72
-
Tidskriftsartikel (refereegranskat)abstract
- Diffuse large B-cell lymphomas (DLBCL) can be subdivided into germinal centre (GC)-like and non-GC-like subtypes by CD10, BCL6 and MUM1/IRF4 status. We previously reported that patients with severe rheumatoid arthritis (RA) are at increased risk of non-GC DLBCL. This study examined a new GC-marker, human germinal-centre-associated lymphoma (HGAL) protein, in RA-DLBCL. Of 111, 38 (34%) DLBCL were HGAL-positive and showed less disseminated disease and a tendency toward improved overall survival compared to HGAL-negative cases. This supports that a majority of RA-DLBCL are of non-GC origin, indicating a specific role for activated peripheral B cells in the pathogenesis of RA-DLBCL.
|
|
| 12. |
|
|
| 13. |
|
|
| 14. |
- Bower, H., et al.
(författare)
-
Effects of the COVID-19 pandemic on patients with inflammatory joint diseases in Sweden: from infection severity to impact on care provision
- 2021
-
Ingår i: Rmd Open. - : BMJ. - 2056-5933. ; 7:3
-
Tidskriftsartikel (refereegranskat)abstract
- Objectives To compare risks for COVID-19-related outcomes in inflammatory joint diseases (IJDs) and across disease-modifying antirheumatic drugs (DMARDs) during the first two waves of the pandemic and to assess effects of the pandemic on rheumatology care provision. Methods Through nationwide multiregister linkages and cohort study design, we defined IJD and DMARD use annually in 2015-2020. We assessed absolute and relative risks of hospitalisation or death listing COVID-19. We also assessed the incidence of IJD and among individuals with IJD, rheumatologist visits, DMARD use and incidence of selected comorbidities. Results Based on 115 317 patients with IJD in 2020, crude risks of hospitalisation and death listing COVID-19 (0.94% and 0.33% across both waves, respectively) were similar during both waves (adjusted HR versus the general population 1.33, 95% CI 1.23 to 1.43, for hospitalisation listing COVID-19; 1.23, 95% CI 1.08 to 1.40 for death listing COVID-19). Overall, biological disease-modifying antirheumatic drugs (bDMARDs)/targeted synthetic disease-modifying antirheumatic drugs (tsDMARDs) did not increase risks of COVID-19 related hospitalisation (with the exception of a potential signal for JAK inhibitors) or death. During the pandemic, decreases were observed for IJD incidence (-7%), visits to rheumatology units (-16%), DMARD dispensations (+6.5% for bDMARD/tsDMARDs and -8.5% for conventional synthetic DMARDs compared with previous years) and for new comorbid conditions, but several of these changes were part of underlying secular trends. Conclusions Patients with IJD are at increased risk of serious COVID-19 outcomes, which may partially be explained by medical conditions other than IJD per se. The SARS-CoV-2 pandemic has exerted measurable effects on aspects of rheumatology care provision demonstrated, the future impact of which will need to be assessed.
|
|
| 15. |
- Bower, Hannah, et al.
(författare)
-
Impact of the COVID-19 pandemic on morbidity and mortality in patients with inflammatory joint diseases and in the general population : a nationwide Swedish cohort study
- 2021
-
Ingår i: Annals of the Rheumatic Diseases. - : BMJ Publishing Group Ltd. - 0003-4967 .- 1468-2060. ; 80:8, s. 1086-1093
-
Tidskriftsartikel (refereegranskat)abstract
- Objectives: To estimate absolute and relative risks for all-cause mortality and for severe COVID-19 in inflammatory joint diseases (IJDs) and with antirheumatic therapies.Methods: Through Swedish nationwide multiregister linkages, we selected all adult patients with rheumatoid arthritis (RA, n=53 455 in March 2020), other IJDs (here: spondyloarthropathies, psoriatic arthritis and juvenile idiopathic arthritis, n=57 112), their antirheumatic drug use, and individually matched population referents. We compared annual all-cause mortality March-September 2015 through 2020 within and across cohorts, and assessed absolute and relative risks for hospitalisation, admission to intensive care and death due to COVID-19 March-September 2020, using Cox regression.Results: During March-September 2020, the absolute all-cause mortality in RA and in other IJDs was higher than 2015-2019, but relative risks versus the general population (around 2 and 1.5) remained similar during 2020 compared with 2015-2019. Among patients with IJD, the risks of hospitalisation (0.5% vs 0.3% in their population referents), admission to intensive care (0.04% vs 0.03%) and death (0.10% vs 0.07%) due to COVID-19 were low. Antirheumatic drugs were not associated with increased risk of serious COVID-19 outcomes, although for certain drugs, precision was limited.Conclusions: Risks of severe COVID-19-related outcomes were increased among patients with IJDs, but risk increases were also seen for non-COVID-19 morbidity. Overall absolute and excess risks are low and the level of risk increases are largely proportionate to those in the general population, and explained by comorbidities. With possible exceptions, antirheumatic drugs do not have a major impact on these risks.
|
|
| 16. |
|
|
| 17. |
- Fagerlind, Hanna, et al.
(författare)
-
Patients' understanding of the concepts of health and quality of life
- 2010
-
Ingår i: Patient Education and Counseling. - : Elsevier BV. - 0738-3991 .- 1873-5134. ; 78:1, s. 104-110
-
Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: The aim of this study was to identify how persons' with rheumatoid arthritis (RA) understand the concepts of health and quality of life (QoL). METHODS: A phenomenograpic approach was used to gauge variations in understanding of health and QoL. Semistructured interviews were conducted with 22 persons having RA. The interviews were audiotaped, transcribed verbatim, and analyzed, resulting in a descriptive system consisting of categories and subcategories. RESULTS: Health was primarily associated with being healthy/being free from disease, being able to function normally, experiencing well-being, and having a healthy lifestyle. Two above-mentioned domains, "being healthy" and "being able to function normally" overlapped with respondents' understanding of QoL. Additional perceived domains included attitudes towards life and, social and physical environments. CONCLUSION: The results show that patients' understanding of the two concepts of health and QoL partially overlap and partially differ. PRACTICE IMPLICATIONS: Patients' understanding of the concepts is individual and diverse, which needs to be taken into account in patient-physician consultations to ensure good communication. Furthermore, the interpretation of results based on patient-reported outcomes instruments measuring health status and/or QoL needs to be further studied over time to identify possible changes in these conceptions.
|
|
| 18. |
|
|
| 19. |
|
|
| 20. |
- Feltelius, Nils, et al.
(författare)
-
Utility of registries for post-marketing evaluation of medicines. A survey of Swedish health care quality registries from a regulatory perspective.
- 2017
-
Ingår i: Upsala Journal of Medical Sciences. - : Uppsala Medical Society. - 0300-9734 .- 2000-1967. ; 122:2, s. 136-147
-
Tidskriftsartikel (refereegranskat)abstract
- AIM: The aim of this study was to describe content and procedures in some selected Swedish health care quality registries (QRs) of relevance to regulatory decision-making.METHODS: A workshop was organized with participation of seven Swedish QRs which subsequently answered a questionnaire regarding registry content on drug treatments and outcomes. Patient populations, coverage, data handling and quality control, as well as legal and ethical aspects are presented. Scientific publications from the QRs are used as a complementary measure of quality and scientific relevance.RESULTS: The registries under study collect clinical data of high relevance to regulatory and health technology agencies. Five out of seven registries provide information on the drug of interest. When applying external quality criteria, we found a high degree of fulfillment, although information on medication was not sufficient to answer all questions of regulatory interest. A notable strength is the option for linkage to the Prescribed Drug Registry and to information on education and socioeconomic status. Data on drugs used during hospitalization were also collected to some extent. Outcome measures collected resemble those used in relevant clinical trials. All registries collected patient-reported outcome measures. The number of publications from the registries was substantial, with studies of appropriate design, including randomized registry trials.CONCLUSIONS: Quality registries may provide a valuable source of post-marketing data on drug effectiveness, safety, and cost-effectiveness. Closer collaboration between registries and regulators to improve quality and usefulness of registry data could benefit both regulatory utility and value for health care providers.
|
|
| 21. |
- Frisell, Thomas, et al.
(författare)
-
Comparative effectiveness of abatacept, rituximab, tocilizumab and TNFi biologics in RA : Results from the nationwide Swedish register
- 2019
-
Ingår i: Rheumatology (United Kingdom). - : Oxford University Press (OUP). - 1462-0324 .- 1462-0332. ; 58:8, s. 1367-1377
-
Tidskriftsartikel (refereegranskat)abstract
- Objectives: Current guidelines rank abatacept, rituximab, tocilizumab and TNF-inhibitors (TNFi) as having equal effectiveness for the treatment of RA, at least as second line therapies. These recommendations are mainly based on meta-analysis of randomized controlled trials, with few direct drug-drug comparisons. Our objective was to compare the real-world absolute and relative effectiveness among RA patients starting any of the available biologic DMARDs (bDMARDs). Methods: We used the Swedish Rheumatology Register to identify patients with RA initiating TNFi, rituximab, abatacept or tocilizumab in 2010-2016 as first bDMARD (n = 9333), or after switch from TNFi as first bDMARD (n = 3941). National Swedish registers provided additional covariates and censoring events. Effectiveness was assessed 3 and 12 months after treatment start, as the proportion remaining on therapy and with EULAR Good Response, HAQ improvement >0.2, zero swollen/tender joints and CDAI remission. Adjusted differences were estimated with multivariable linear regression. Results: Patients starting non-TNFi (vs TNFi) as first bDMARD had a higher proportion remaining on drug and reaching most response outcomes as first bDMARD (1-year EULAR Good Response/HAQ improvement: TNFi 24.9/25.4%, rituximab 28.6/37.2%, abatacept 31.9/33.7%, tocilizumab 50.9/43.1%). After switch from a first TNFi, rituximab and tocilizumab, but not abatacept, were associated with significantly better response measures than TNFi (1-year EULAR Good Response/HAQ improvement: TNFi 11.6/16.1%, rituximab 24.8/33.2%, abatacept 13.1/17.5%, tocilizumab 34.1/29.4%). Differences remained significant after adjusting for potential confounders. Conclusion: Treatment outcomes among RA patients treated in Swedish clinical practice are in line with a superior effectiveness of non-TNFi bDMARDs, in particular tocilizumab and rituximab, compared with TNFi.
|
|
| 22. |
- Frisell, T., et al.
(författare)
-
Safety of biological and targeted synthetic disease-modifying antirheumatic drugs for rheumatoid arthritis as used in clinical practice: results from the ARTIS programme
- 2023
-
Ingår i: Annals of the Rheumatic Diseases. - : BMJ. - 0003-4967 .- 1468-2060. ; 82:5
-
Tidskriftsartikel (refereegranskat)abstract
- ObjectiveLongitudinal clinical registry-infrastructures such as Anti-Rheumatic Therapies in Sweden (ARTIS) allow simultaneous comparison of the safety of individual immunomodulatory drugs used in clinical practice, with consistent definitions of treatment cohorts, follow-up and outcomes. Our objective was to assess and compare incidence rates of key safety outcomes for individual targeted synthetic or biological disease-modifying antirheumatic drugs (b/ts DMARDs) in rheumatoid arthritis (RA), updating previous reports and including newer treatments including Janus Kinase inhibitors (JAKi). MethodsNationwide register-based cohort study including all patients with RA in Sweden registered as starting any b/tsDMARD 1 January 2010 through 31 December 2020, followed until 30 June 2021 (N=20 117). The incidence rates of selected outcomes, identified through national healthcare registers, were compared between individual b/tsDMARDs, adjusted for confounding by demographics, RA disease characteristics and comorbidity. ResultsThere were marked differences in treatment discontinuations due to adverse events (rates per 1000 person-years ranged from 18 on rituximab to 57 on tofacitinib), but few significant differences were observed for the serious adverse events under study. Neither cardiovascular events nor general serious infections were more frequent on baricitinib or tofacitinib versus bDMARDs, but JAKi were associated with higher rates of hospital-treated herpes zoster (HR vs etanercept, 3.82 (95% CI 2.05 to 7.09) and 4.00 (1.59 to 10.06)). Low number of events limited some comparisons, in particular for sarilumab and tofacitinib. ConclusionData from ARTIS supports that the b/tsDMARDs currently used to treat RA have acceptable and largely similar safety profiles, but differences exist in particular concerning tolerability and specific infection risks.
|
|
| 23. |
- Fryzek, Jon P., et al.
(författare)
-
Self-reported symptoms among women after cosmetic breast implant and breast reduction surgery
- 2001
-
Ingår i: Plastic and Reconstructive Surgery. - : Ovid Technologies (Wolters Kluwer Health). - 0032-1052. ; 107:1, s. 206-213
-
Tidskriftsartikel (refereegranskat)abstract
- A retrospective cohort study was performed in Sweden to evaluate the possibility that an individual symptom or constellation of illness symptoms related to silicone occurs in women after breast implant surgery. A random sample (n = 2500) of all women in the Swedish national implant registry who underwent breast augmentation surgery with alloplastic breast implants during the years 1965 through 1993 was compared with a sample (n = 3500) of women who underwent breast reduction surgery during the same period, frequency matched to the implant patients for age and calendar year at the time of surgery. In total, 65 percent of the breast implant patients (n = 1546) and 72 percent of the breast reduction patients (n = 2496) completed a self-administered questionnaire covering 28 rheumatologic and other symptoms and lifestyle and demographic factors. Practically all of the 28 symptoms inquired about were reported more often by women in the breast implant cohort, with 16 (57 percent) significantly more common in breast implant recipients. In contrast, few significant differences or consistent patterns were observed in the length of time since the implant and in the type (silicone or saline) or volume of the implant. Although women with breast implants report a multitude of symptoms more often than women who have breast reduction surgery, the lack of specificity and absence of dose-response relationships suggest that the excess of reported symptoms is not causally related to cosmetic implants.
|
|
| 24. |
- Gedeborg, Rolf, et al.
(författare)
-
Federated analyses of multiple data sources in drug safety studies
- 2023
-
Ingår i: Pharmacoepidemiology and Drug Safety. - : John Wiley & Sons. - 1053-8569 .- 1099-1557. ; 32:3, s. 279-286
-
Forskningsöversikt (refereegranskat)abstract
- PurposeStudies of rare side effects of new drugs with limited exposure may require pooling of multiple data sources. Federated Analyses (FA) allow real-time, interactive, centralized statistical processing of individual-level data from different data sets without transfer of sensitive personal data.MethodsWe review IT-architecture, legal considerations, and statistical methods in FA, based on a Swedish Medical Products Agency methodological development project.ResultsIn a review of all post-authorisation safety studies assessed by the EMA during 2019, 74% (20/27 studies) reported issues with lack of precision in spite of mean study periods of 9.3 years. FA could potentially improve precision in such studies. Depending on the statistical model, the federated approach can generate identical results to a standard analysis. FA may be particularly attractive for repeated collaborative projects where data is regularly updated. There are also important limitations. Detailed agreements between involved parties are strongly recommended to anticipate potential issues and conflicts, document a shared understanding of the project, and fully comply with legal obligations regarding ethics and data protection. FA do not remove the data harmonisation step, which remains essential and often cumbersome. Reliable support for technical integration with the local server architecture and security solutions is required. Common statistical methods are available, but adaptations may be required.ConclusionsFederated Analyses require competent and active involvement of all collaborating parties but have the potential to facilitate collaboration across institutional and national borders and improve the precision of postmarketing drug safety studies.
|
|
| 25. |
- Gedeborg, Rolf, et al.
(författare)
-
Increased availability of paracetamol in Sweden and incidence of paracetamol poisoning : using laboratory data to increase validity of a population-based registry study
- 2017
-
Ingår i: Pharmacoepidemiology and Drug Safety. - : WILEY. - 1053-8569 .- 1099-1557. ; 26:5, s. 518-527
-
Tidskriftsartikel (refereegranskat)abstract
- Purpose: To estimate the incidence trend and outcome of paracetamol poisoning, in relation to increased availability of paracetamol from non-pharmacy outlets in 2009.Method: Patients' serum paracetamol results over 14years (2000-2013) from 20 (out of 21) regions in Sweden were linked to national registers of hospital care, cause of death, and prescriptions. Paracetamol poisonings were defined by serum paracetamol levels, hospital diagnoses, or cause of death. The change in incidence of poisonings following increased availability of paracetamol was analysed by using segmental regression of time series.Results: Of the 12068 paracetamol poisonings, 85% were classified as intentional self-harm. Following increased availability from non-pharmacy outlets, there was a 40.5% increase in the incidence of paracetamol poisoning, from 11.5/100000 in 2009 to 16.2/100000 in 2013. Regression analyses indicated a change in the trend (p<0.0001) but not an immediate jump in the incidence (p=0.5991) following the increased availability. Adjusting for trends in hospital episodes for self-harm, suicides, and the sales volume of paracetamol did not influence the result. All-cause mortality at 30days (3.2%) did not change over time.Conclusions: The incidence of paracetamol poisoning in Sweden has increased since 2009, contrasting the decreased incidence in the period of 2007-2009. The change in trend was temporally associated with the introduction of availability of paracetamol from non-pharmacy outlets but did not appear to be related to sales volume of paracetamol or general trends in self-harm or suicides.
|
|
| 26. |
- Gedeborg, Rolf, et al.
(författare)
-
Validation of myocarditis diagnoses in the Swedish patient register for analyses of potential adverse reactions to COVID-19 vaccines
- 2023
-
Ingår i: Upsala Journal of Medical Sciences. - : Upsala Medical Society. - 0300-9734 .- 2000-1967. ; 128:1
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Coronavirus disease 2019 (COVID-19) mRNA vaccines are associated with an increased risk of myocarditis using hospital discharge diagnoses as an outcome. The validity of these register-based diagnoses is uncertain.Methods: Patient records for subjects < 40 years of age and a diagnosis of myocarditis in the Swedish National Patient Register were manually reviewed. Brighton Collaboration diagnosis criteria for myocarditis were applied based on patient history, clinical examination, laboratory data, electrocardiograms, echocardiography, magnetic resonance imaging and myocardial biopsy. Poisson regression was used to estimate incidence rate ratios, comparing the register-based outcome variable to validated outcomes. Interrater reliability was assessed by a blinded re-evaluation.Results: Overall, 95.6% (327/342) of cases registered as myocarditis were confirmed (definite, probable or possible myocarditis according to Brighton Collaboration diagnosis criteria, positive predictive value 0.96 [95% CI 0.93–0.98]). Of the 4.4% (15/342) cases reclassified as no myocarditis or as insufficient information, two cases had been exposed to the COVID-19 vaccine no more than 28 days before the myocarditis diagnosis, two cases were exposed >28 days before admission and 11 cases were unexposed to the vaccine. The reclassification had only minor impact on incidence rate ratios for myocarditis following COVID-19 vaccination. In total, 51 cases were sampled for a blinded re-evaluation. Of the 30 randomly sampled cases initially classified as either definite or probably myocarditis, none were re-classified after re-evaluation. Of the in all 15 cases initially classified as no myocarditis or insufficient information, 7 were after re-evaluation re-classified as probable or possible myocarditis. This re-classification was mostly due to substantial variability in electrocardiogram interpretation.Conclusion: This validation of register-based diagnoses of myocarditis by manual patient record review confirmed the register diagnosis in 96% of cases and had high interrater reliability. Reclassification had only a minor impact on the incidence rate ratios for myocarditis following COVID-19 vaccination.
|
|
| 27. |
|
|
| 28. |
- Hallböök, Tove, et al.
(författare)
-
Narkolepsi – ovanlig sjukdomsom fått ökad uppmärksamhet : Pandemrixvaccination ledde till fler insjuknanden bland barn och ungdomar
- 2014
-
Ingår i: Läkartidningen. - 0023-7205 .- 1652-7518. ; 111:41, s. 1770-1773
-
Tidskriftsartikel (refereegranskat)abstract
- Narkolepsi är en ovanlig sjukdom där symtomen beror på störd reglering av sömn och vakenhet. Kardinalsymtom är uttalad dagsömnighet, kataplexiattacker och nattlig dyssomni. Etiologin anses betingad av en autoimmun process hos predisponerade individer, där omgivningsfaktorer är av betydelse för att utlösa sjukdomen.Pandemrixvaccinationen ledde till ökat insjuknande hos barn och ungdomar och en viss ökning hos unga vuxna.Behandlingen utgör en kombination av läkemedel med effekt på kardinalsymtomen och livsstilsråd, där teamomhändertagande är viktigt.Svenska narkolepsiregistret ger möjlighet att följa sjukdomsförlopp och behandling, vilket är viktigt inte minst eftersom dokumentationen av de läkemedel som används är begränsad.
|
|
| 29. |
|
|
| 30. |
- Hansson, Mats G, et al.
(författare)
-
Medical registries represent vital patient interests and should not be dismantled by stricter regulation
- 2012
-
Ingår i: Cancer Epidemiology. - : Elsevier BV. - 1877-7821 .- 1877-783X. ; 36:6, s. 575-578
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND:Medical registries serve patients as beneficiaries of quality standards and new treatment opportunities. However, it has been argued that registries threaten patient privacy interests and should therefore be more strictly regulated.METHODS AND RESULTS:With the European Treatment and Outcome Study for Chronic Myeloid Leukemia as a concrete example we identify and describe how four of the major arguments put forward for stricter regulation fail.CONCLUSION:We conclude that medical registries should be promoted both for research and quality control, and that the regulatory bureaucratic burden should be reduced.
|
|
| 31. |
- Hellgren, Karin, et al.
(författare)
-
Do rheumatoid arthritis and lymphoma share risk factors? : A comparison of lymphoma and cancer risks before and after diagnosis of rheumatoid arthritis
- 2010
-
Ingår i: Arthritis and Rheumatism. - : Wiley. - 0004-3591 .- 1529-0131. ; 62:5, s. 1252-1258
-
Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: Patients with rheumatoid arthritis (RA), in particular those with the most severe disease, are at increased risk of malignant lymphoma. Whether this increase is entirely consequential to the RA disease and/or its treatment or reflective of shared susceptibility to the two diseases remains unclear. To resolve this, we assessed whether patients with RA are at increased risk of lymphoma or of other cancers, already before diagnosis of RA, and if the relative risk increases with time since RA diagnosis.METHODS: 6,745 patients with incident RA (ACR criteria, symptom duration < 1 year) registered in the Swedish Early RA register from 1997 through 2006 were identified. For each patient, five general population controls were randomly matched by gender, age, marital status and residence (n=33,657). All individuals were linked to the nationwide Swedish Cancer Register 1958-2006. Relative risks (RR) of lymphoma and cancer overall before and after the diagnosis of RA were estimated using conditional logistic and Cox regression, respectively.RESULTS: Before diagnosis of RA, no increased risk of lymphoma (RR= 0.67, 95% CI 0.37-1.23) or other cancers (RR= 0.78, 95% CI 0.70-0.88) was observed. During the first ten years following diagnosis of RA, the overall RR of lymphoma was 1.75 (95 % CI 1.04-2.96).CONCLUSION: Overall, a history of cancer, lymphoma included, does not increase the risk of subsequent RA development. Shared susceptibility for RA and lymphoma may thus be of limited importance. By contrast increased lymphoma risks were observed already within the first decade following RA diagnosis.
|
|
| 32. |
- Hellgren, Karin, et al.
(författare)
-
Rheumatoid arthritis, treatment with corticosteroids, and risk of malignant lymphomas : results from a case-control study
- 2010
-
Ingår i: Annals of the Rheumatic Diseases. - : BMJ. - 0003-4967 .- 1468-2060. ; 69:4, s. 654-659
-
Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE:Benefits and risks of corticosteroid treatment in rheumatoid arthritis (RA) are debated. Patients with RA are at increased risk of malignant lymphomas. In a large case-control study of risk factors for lymphoma in RA, we recently reported that steroid treatment was associated with decreased lymphoma risk. This study sought to further assess the nature of this association.METHODS:In a cohort of 74,651 patients with RA, we identified 378 cases with lymphoma and 378 matched RA controls, and abstracted information on inflammatory activity and different aspects of steroid treatment (duration, therapeutic strategy and mode of administration) from their medical records. Lymphomas were reclassified (WHO classification) and examined for Epstein-Barr virus. Relative risks were assessed as adjusted odds ratios (OR) through conditional logistic regression.RESULTS:A total duration of oral steroid treatment less than two years was not associated with lymphoma risk (OR=0.87; 95% confidence interval [CI] 0.51-1.5), whereas total treatment longer than two years was associated with a lower lymphoma risk (OR= 0.43; 95% CI 0.26-0.72). RA duration at the initiation of oral steroids did not affect lymphoma risk. Intra-articular steroids were associated with a reduced lymphoma risk, but only when used as swift flare therapy (OR= 0.22; 95% CI 0.13-0.37). Analyses by lymphoma subtype showed a reduced risk of diffuse large B-cell lymphoma (crude OR=0.59; 95% CI 0.37-0.94).CONCLUSION:In this RA population, use of steroids was associated with reduced lymphoma risk. Whether this association is a generic effect of steroids or specific to the studied population remains unknown.
|
|
| 33. |
- Holmen, Carolina, et al.
(författare)
-
A Swedish national post-marketing surveillance study of natalizumab treatment in multiple sclerosis
- 2011
-
Ingår i: Multiple Sclerosis Journal. - : SAGE Publications. - 1477-0970 .- 1352-4585. ; 17:6, s. 708-719
-
Tidskriftsartikel (refereegranskat)abstract
- Background: A post marketing surveillance study was conducted to evaluate safety and efficacy of natalizumab in Swedish multiple sclerosis (MS) patients since its introduction in August 2006 until March 2010. Methods: Patients were registered in the web-based Swedish MS-registry at 40 locations and evaluated every 6 months. Adverse events and clinical outcomes were recorded. Results: One thousand one hundred and fifty-two patients were included (71.4% female) and 149 patients stopped treatment; the main reason was planned pregnancy. Anti-natalizumab antibodies were found in 4.5% (52 patients) of which 1.6% displayed persistent antibodies. Serious adverse events were rare, but included three cases with progressive multifocal leukoencephalopathy (PML). There were seven fatal cases, probably unrelated to the natalizumab treatment. For relapsing-remitting MS patients (n = 901), mean Expanded Disability Status Scale (EDSS, -10.7%), Multiple Sclerosis Severity Scale (MSSS, -20.4%), Multiple Sclerosis Impact Scale (MSIS-29, physical -9.9%, psychological -13.3%) and Symbol Digit Modalities Test (SDMT, +10.7%) all showed significant improvements during 24 months of treatment with natalizumab. The Swedish web-based MS quality registry proved to function as a platform for post-marketing MS drug surveillance, providing long-term data regarding drug effects and adverse events beyond clinical trials. Conclusions: Our results indicate that natalizumab is generally well tolerated and has sustained efficacy for patients with active MS, though the risk of PML is still an important concern.
|
|
| 34. |
- Kapetanovic, Meliha C., et al.
(författare)
-
Ny diagnostik och behandling vid gikt
- 2016
-
Ingår i: Läkartidningen. - 0023-7205. ; 113:34-35
-
Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
|
|
| 35. |
- Ljung, Lotta, et al.
(författare)
-
Response to biological treatment and subsequent risk of coronary events in rheumatoid arthritis
- 2016
-
Ingår i: Annals of the Rheumatic Diseases. - : BMJ. - 0003-4967 .- 1468-2060. ; 75:12, s. 2087-2094
-
Tidskriftsartikel (refereegranskat)abstract
- Objectives Whether the increased risk of comorbidities, such as cardiovascular disease, in rheumatoid arthritis (RA) can be reverted by particular antirheumatic therapies, or response to these, is unclear but of critical clinical importance. We wanted to investigate whether response to tumour necrosis factor inhibitors (TNFi) translates into a reduced risk for acute coronary syndrome (ACS). Methods A cohort of patients with RA initiating a first TNFi 2001-2012 was identified in the Swedish Biologics Register. The association between European League Against Rheumatism (EULAR) response after 3-8 months of treatment (assessed using the first, the best and the measurement closest to 5 months, respectively), and the risk of incident ACS during the subsequent year was analysed in Cox regression models. Adjustments included cardiovascular risk factors, joint surgery, RA duration, education and work disability. Results During 6592 person-years among TNFi initiators (n=6864, mean age 55 years, 77% women), 47 ACS occurred. The adjusted HRs (95% CI), which were similar to the crude HRs, of the 1-year risk of ACS among EULAR good responders compared with non-responders were 0.5 (0.2 to 1.4), 0.4 (0.2 to 0.9) and 0.5 (0.2 to 1.2), for the first, the best and the evaluation closest to 5 months, respectively. EULAR moderate responders had equal risk to that of EULAR non-responders, who, compared with the general population referents (n=34 229), had a more than twice the risk of ACS. For good responders, there was no statistically significant difference in risk versus the general population. Conclusions Optimised RA disease control has the potential to revert otherwise increased risks for ACS in RA.
|
|
| 36. |
- Ludvigsson, Jonas F., 1969-, et al.
(författare)
-
Maternal vaccination against H1N1 influenza and offspring mortality : population based cohort study and sibling design
- 2015
-
Ingår i: BMJ. British Medical Journal. - London, United Kingdom : BMJ Publishing Group Ltd. - 0959-8146 .- 0959-535X. ; 351
-
Tidskriftsartikel (refereegranskat)abstract
- Study question: What is the mortality in offspring of mothers who hadinfluenza A(H1N1)pdm09 vaccination during pregnancy?Methods: This was a prospective population based cohort study in seven healthcare regions in Sweden based on vaccinations taking place between 2 October 2009 and 26 November 2010. H1N1 vaccination data were linked with pregnancy and birth characteristics and offspring mortality data in 275 500 births (of which 1203 were stillbirths) from 137 886 mothers. Of these offspring, 41 183 had been exposed to vaccination with Pandemrix, a monovalent AS03 adjuvanted H1N1 influenza vaccine, during fetal life. A primary comparison group consisted of pregnancies of women who were not vaccinated during the same calendar period. In a second comparison, non-exposed siblings of infants prenatally exposed to vaccination were used as controls. Cox regression was used to estimate hazard ratios for stillbirth, early neonatal mortality (days 0-6 after birth), and subsequent mortality (beginning on day 7) in vaccinated versus nonvaccinated women, adjusting for mother’s age at delivery, body mass index, parity, smoking, country of birth, and disposable income and for sex of offspring.Study answer and limitations: The results of this study suggest that AS03 adjuvanted H1N1 vaccination during pregnancy does not affect the risk of stillbirth, early neonatal death, or later mortality in the offspring. During follow-up, 1172 stillbirths, 380 early neonatal deaths, and 706 deaths thereafter occurred. Compared with general population controls, this corresponded to adjusted hazard ratios of 0.83 (95% confidence interval 0.65 to 1.04) for stillbirth, 0.71 (0.44 to 1.14) for early neonatal death, and 0.97 (0.69 to 1.36) for later death. When siblings were used as controls, adjusted hazard ratios were 0.88 (0.59 to 1.30) for stillbirth, 0.82 (0.46 to 1.49) for early neonatal death, and 0.78 (0.52 to 1.19) for later death. Limitations of the study include lack of data on miscarriage before gestational week 22, inability to ascertain which mothers had pandemic flu during pregnancy, and lack of data on factors influencing the decision to vaccinate during pregnancy.What this study adds: H1N1 vaccination during pregnancy is not associated with adverse fetal outcome or offspring mortality, including when familial factors are taken into account.
|
|
| 37. |
- Ludvigsson, Jonas F., 1969-, et al.
(författare)
-
Risk for Congenital Malformation With H1N1 Influenza Vaccine : A Cohort Study With Sibling Analysis
- 2016
-
Ingår i: Annals of Internal Medicine. - Philadelphia, USA : American College of Physicians. - 0003-4819 .- 1539-3704. ; 165:12, s. 848-855
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Earlier studies reporting varying risk estimates for congenital malformation in offspring of mothers undergoing vaccination against H1N1 influenza during pregnancy did not consider the potential role of confounding by familial (genetic and shared environmental) factors.Objective: To evaluate an association between maternal H1N1 vaccination during pregnancy and offspring malformation, with familial factors taken into account.Design: Population-based prospective study.Setting: Sweden.Participants: Liveborn offspring born between 1 October 2009 and 1 October 2011 to mothers receiving monovalent AS03-adjuvanted H1N1 influenza vaccine (Pandemrix [GlaxoSmithKline]) during pregnancy. A total of 40 983 offspring were prenatally exposed to the vaccine, 14 385 were exposed within the first trimester (14 weeks), and 7502 were exposed during the first 8 weeks of pregnancy. Exposed offspring were compared with 197 588 unexposed offspring. Corresponding risks in exposed versus unexposed siblings were also estimated.Measurements: Congenital malformation, with subanalyses for congenital heart disease, oral cleft, and limb deficiency.Results: Congenital malformation was observed in 2037 (4.97%) exposed offspring and 9443 (4.78%) unexposed offspring. Adjusted risk for congenital malformation was 4.98% in exposed offspring versus 4.96% in unexposed offspring (risk difference, 0.02% [95% CI, -0.26% to 0.30%]). The corresponding risk differences were 0.16% (CI, -0.23% to 0.56%) for vaccination during the first trimester and 0.10% (CI, -0.41% to 0.62%) for vaccination in the first 8 weeks. Using siblings as comparators yielded no statistically significant risk differences.Limitations: The study was based on live births, and the possibility that data on miscarriage or induced abortion could have influenced the findings cannot be ruled out. Study power was limited in analyses of specific malformations.Conclusion: When intrafamilial factors were taken into consideration, H1N1 vaccination during pregnancy did not seem to be linked to overall congenital malformation in offspring, although risk increases for specific malformations could not be ruled out completely.
|
|
| 38. |
- Simard, Julia F., et al.
(författare)
-
Ten years with biologics : to whom do data on effectiveness and safety apply?
- 2011
-
Ingår i: Rheumatology. - : Oxford University Press (OUP). - 1462-0324 .- 1462-0332. ; 50:1, s. 204-213
-
Tidskriftsartikel (refereegranskat)abstract
- Methods. We identified all adult patients with RA (n = 9612), PsA (n = 1417) and other SpA (n = 1652) initiating a first biologic therapy between 1 January 1999 and 31 December 2008, registered in the Swedish Biologics Register (ARTIS), including information on demographics, disease characteristics and 1-year risk of first-line treatment discontinuation. Results. Over calendar time, measures of disease activity at start declined substantially for all indications, and diminished between first-, second- and third-line therapy starts. One-year risks of first-line therapy discontinuation increased. Switchers to anti-TNF and non-TNF biologics had different comorbidities. Despite < 50% drug retention at 5 years, most patients remained exposed to some biologic. Conclusions. The trends in baseline characteristics and drug retention underscores that any effects of biologics, including comparison between different biologics, must be interpreted in light of the characteristics of the population treated. The observed differences further call for continued vigilance to properly evaluate the safety profiles of biologic treatments as they are currently used. Exposure to multiple biologics presents a challenge for attribution of long-term effects.
|
|
| 39. |
|
|
