| 1. |
- 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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| 2. |
- 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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| 3. |
- Lekander, Ingrid, et al.
(författare)
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The cost-effectiveness of TNF-inhibitors for the treatment of rheumatoid arthritis in Swedish clinical practice
- 2013
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Ingår i: European Journal of Health Economics. - : Springer Science and Business Media LLC. - 1618-7601 .- 1618-7598. ; 14:6, s. 863-873
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Tidskriftsartikel (refereegranskat)abstract
- The objective was to estimate the cost-effectiveness of TNF-inhibitors for the treatment of rheumatoid arthritis in Swedish clinical practice, both as a first and second biological treatment, with or without the combination of conventional DMARDs. Further sub-group analysis of etanercept treatment was performed. Patient level data were obtained from three regions of the Swedish Rheumatology Registers. The dataset contained 2,558 patients who had started TNF-inhibitor treatment, 1,049 with etanercept as their first biological treatment. A total of 819 patients had switched to a second TNF-inhibitor, of which 425 to etanercept. A Markov cohort model was used in which health states of disease severity were classified according to HAQ and DAS28. Disease progression and discontinuation rates of TNF-inhibitors were based on the registry and for the comparator on published literature. Mortality, costs and utilities were based on Swedish data. The main analysis had a societal perspective over 20 years and efficacy was measured in quality-adjusted life-years (QALYs). TNF-inhibitor treatment was associated with an increase in QALYs and an incremental cost compared to no biological treatment. The cost per QALY gained with the three TNF-inhibitors ranged from a,not sign50,000 to a,not sign120,000, with lower estimates for TNF-inhibitors used in combination with MTX and as a first biologic. At a progression of 0.045 for the comparator, most values remain within the accepted range for cost-effectiveness. These results demonstrate that the cost per QALY for TNF-inhibitors was higher than in previous assessments based on registry data and that the results were sensitive to the HAQ progression of the comparator.
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| 4. |
- Lysholm, Fredrik, 1981-
(författare)
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Bioinformatic methods for characterization of viral pathogens in metagenomic samples
- 2013
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Virus infections impose a huge disease burden on humanity and new viruses are continuously found. As most studies of viral disease are limited to theinvestigation of known viruses, it is important to characterize all circulating viruses. Thus, a broad and unselective exploration of the virus flora would be the most productive development of modern virology. Fueled by the reduction in sequencing costs and the unbiased nature of shotgun sequencing, viral metagenomics has rapidly become the strategy of choice for this exploration.This thesis mainly focuses on improving key methods used in viral metagenomics as well as the complete viral characterization of two sets of samples using these methods. The major methods developed are an efficient automated analysis pipeline for metagenomics data and two novel, more accurate, alignment algorithms for 454 sequencing data. The automated pipeline facilitates rapid, complete and effortless analysis of metagenomics samples, which in turn enables detection of potential pathogens, for instance in patient samples. The two new alignment algorithms developed cover comparisons both against nucleotide and protein databases, while retaining the underlying 454 data representation. Furthermore, a simulator for 454 data was developed in order to evaluate these methods. This simulator is currently the fastest and most complete simulator of 454 data, which enables further development of algorithms and methods. Finally, we have successfully used these methods to fully characterize a multitude of samples, including samples collected from children suffering from severe lower respiratory tract infections as well as patients diagnosed with chronic fatigue syndrome, both of which presented in this thesis. In these studies, a complete viral characterization has revealed the presence of both expected and unexpected viral pathogens as well as many potential novel viruses.
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| 5. |
- Lysholm, Sara, et al.
(författare)
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Seropositivity rates of zoonotic pathogens in small ruminants and associated public health risks at informal urban markets in Zambia
- 2022
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Ingår i: Acta Tropica. - : Elsevier. - 0001-706X .- 1873-6254. ; 225
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Tidskriftsartikel (refereegranskat)abstract
- Informal livestock markets are an important source of animal-derived proteins for growing urban populations in countries such as Zambia. In parallel, they can also constitute pathways of zoonotic pathogen transmission to humans. This risk is aggravated by limited disease monitoring and poor control systems with regards to biosecurity and public health. The aim of this study was to investigate the risks for spread of zoonotic diseases in Zambia's two largest informal small ruminant markets, located in Lusaka and Kasumbalesa, through combining seroepidemiology with interviews and observations. In April, May and September 2018, serum samples (n = 237) were collected and analysed for antibodies for the zoonotic pathogens Brucella spp., Coxiella (C.) burnetii and Rift Valley fever virus (RVFV), using commercially available enzyme linked immunosorbent assays (ELISA). In addition, slaughterhouse activities were observed and semi-structured interviews and focus group discussions held with slaughterhouse workers and small ruminant traders, focusing on the handling of animals and meat, and the perceptions of zoonotic disease risks at slaughter and consumption. The study found seropositivity rates of 10.1% (95% confidence interval [CI] 6.60–14.7) for Brucella spp., 5.9% (95% CI 3.27–9.71) for C. burnetii, and 0.8% (95% CI 0.10–3.01) for RVFV. Interviews with value chain members and observations at the slaughterhouse revealed unsanitary procedures and multiple occupational hazards for slaughterhouse workers. This study showed that the Zambian informal small ruminant trade system poses risks to public health, and that these risks are exacerbated by a lack of information about food-borne diseases and how associated risks can be mitigated amongst value chain actors. The results of this study can be used to formulate preventive measures to improve informal meat markets and reduce the risks to public health.
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| 6. |
- Sullivan, Patrick F, et al.
(författare)
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An unbiased metagenomic search for infectious agents using monozygotic twins discordantfor chronic fatigue
- 2011
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Ingår i: BMC Microbiology. - : BMC. - 1471-2180. ; 11:2
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Tidskriftsartikel (refereegranskat)abstract
- Background: Chronic fatigue syndrome is an idiopathic syndrome widely suspected of having an infectious orimmune etiology. We applied an unbiased metagenomic approach to try to identify known or novel infectiousagents in the serum of 45 cases with chronic fatigue syndrome or idiopathic chronic fatigue. Controls were theunaffected monozygotic co-twins of cases, and serum samples were obtained at the same place and time.Results: No novel DNA or RNA viral signatures were confidently identified. Four affected twins and no unaffectedtwins evidenced viremia with GB virus C (8.9% vs. 0%, p = 0.019), and one affected twin had previously undetectedhepatitis C viremia. An excess of GB virus C viremia in cases with chronic fatigue requires confirmation.Conclusions: Current, impairing chronic fatigue was not robustly associated with viremia detectable in serum.
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