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- Hetland, M. L., et al.
(författare)
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Active conventional treatment and three different biological treatments in early rheumatoid arthritis: phase IV investigator initiated, randomised, observer blinded clinical trial
- 2020
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Ingår i: Bmj-British Medical Journal. - : BMJ. - 1756-1833. ; 371
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE To evaluate and compare benefits and harms of three biological treatments with different modes of action versus active conventional treatment in patients with early rheumatoid arthritis. DESIGN Investigator initiated, randomised, open label, blinded assessor, multiarm, phase IV study. SETTING Twenty nine rheumatology departments in Sweden, Denmark, Norway, Finland, the Netherlands, and Iceland between 2012 and 2018. PARTICIPANTS Patients aged 18 years and older with treatment naive rheumatoid arthritis, symptom duration less than 24 months, moderate to severe disease activity, and rheumatoid factor or anti-citrullinated protein antibody positivity, or increased C reactive protein. INTERVENTIONS Randomised 1:1:1:1, stratified by country, sex, and anti-citrullinated protein antibody status. All participants started methotrexate combined with (a) active conventional treatment (either prednisolone tapered to 5 mg/day, or sulfasalazine combined with hydroxychloroquine and intraarticular corticosteroids), (b) certolizumab pegol, (c) abatacept, or (d) tocilizumab. MAIN OUTCOME MEASURES The primary outcome was adjusted clinical disease activity index remission (CDAI <= 2.8) at 24 weeks with active conventional treatment as the reference. Key secondary outcomes and analyses included CDAI remission at 12 weeks and over time, other remission criteria, a non-inferiority analysis, and harms. RESULTS 812 patients underwent randomisation. The mean age was 54.3 years (standard deviation 14.7) and 68.8% were women. Baseline disease activity score of 28 joints was 5.0 (standard deviation 1.1). Adjusted 24 week CDAI remission rates were 42.7% (95% confidence interval 36.1% to 49.3%) for active conventional treatment, 46.5% (39.9% to 53.1%) for certolizumab pegol, 52.0% (45.5% to 58.6%) for abatacept, and 42.1% (35.3% to 48.8%) for tocilizumab. Corresponding absolute differences were 3.9% (95% confidence interval -5.5% to 13.2%) for certolizumab pegol, 9.4% (0.1% to 18.7%) for abatacept, and -0.6% (-10.1% to 8.9%) for tocilizumab. Key secondary outcomes showed no major differences among the four treatments. Differences in CDAI remission rates for active conventional treatment versus certolizumab pegol and tocilizumab, but not abatacept, remained within the prespecified non-inferiority margin of 15% (per protocol population). The total number of serious adverse events was 13 (percentage of patients who experienced at least one event 5.6%) for active conventional treatment, 20 (8.4%) for certolizumab pegol, 10 (4.9%) for abatacept, and 10 (4.9%) for tocilizumab. Eleven patients treated with abatacept stopped treatment early compared with 20-23 patients in the other arms. CONCLUSIONS All four treatments achieved high remission rates. Higher CDAI remission rate was observed for abatacept versus active conventional treatment, but not for certolizumab pegol or tocilizumab versus active conventional treatment. Other remission rates were similar across treatments. Non-inferiority analysis indicated that active conventional treatment was non-inferior to certolizumab pegol and tocilizumab, but not to abatacept. The results highlight the efficacy and safety of active conventional treatment based on methotrexate combined with corticosteroids, with nominally better results for abatacept, in treatment naive early rheumatoid arthritis.
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- Fedorov, R V, et al.
(författare)
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Structure of ribosomal protein TL5 complexed with RNA provides new insights into the CTC family of stress proteins
- 2001
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Ingår i: Acta Crystallographica. Section D: Biological Crystallography. - 1399-0047. ; D57:7, s. 968-976
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Tidskriftsartikel (refereegranskat)abstract
- The crystal structure of Thermus thermophilus ribosomal protein TL5 in complex with a fragment of Escherichia coli 5S rRNA has been determined at 2.3 Å resolution. The protein consists of two domains. The structure of the N-terminal domain is close to the structure of E. coli ribosomal protein L25, but the C-terminal domain represents a new fold composed of seven -strands connected by long loops. TL5 binds to the RNA through its N-terminal domain, whereas the C-terminal domain is not included in this interaction. Cd2+ ions, the presence of which improved the crystal quality significantly, bind only to the protein component of the complex and stabilize the protein molecule itself and the interactions between the two molecules in the asymmetric unit of the crystal. The TL5 sequence reveals homology to the so-called general stress protein CTC. The hydrophobic cores which stabilize both TL5 domains are highly conserved in CTC proteins. Thus, all CTC proteins may fold with a topology close to that of TL5.
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- Kristensen, O, et al.
(författare)
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Structural characterization of the stringent response related exopolyphosphatase/guanosine pentaphosphate phosphohydrolase protein family
- 2004
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Ingår i: Biochemistry. - : American Chemical Society (ACS). - 0006-2960 .- 1520-4995. ; 43:28, s. 8894-8900
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Tidskriftsartikel (refereegranskat)abstract
- Exopolyphosphatase/guanosine pentaphosphate phosphohydrolase (PPX/GPPA) enzymes play central roles in the bacterial stringent response induced by starvation. The high-resolution crystal structure of the putative Aquifex aeolicus PPX/GPPA phosphatase from the actin-like ATPase domain superfamily has been determined, providing the first insights to features of the common catalytic core of the PPX/GPPA family. The protein has a two-domain structure with an active site located in the interdomain cleft. Two crystal forms were investigated (type I and 11) at resolutions of 1.53 and 2.15 Angstrom, respectively. This revealed a structural flexibility that has previously been described as a "butterfly-like" cleft opening around the active site in other actin-like superfamily proteins. A calcium ion is observed at the center of this region in type I crystals, substantiating that PPX/GPPA enzymes use metal ions for catalysis. Structural analysis suggests that nucleotides bind at a similar position to that seen in other members of the superfamily.
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| 27. |
- Nielsen, MB, et al.
(författare)
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Current management of locally recurrent rectal cancer
- 2011
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Ingår i: Colorectal disease : the official journal of the Association of Coloproctology of Great Britain and Ireland. - : Wiley. - 1463-1318. ; 13:7, s. 732-742
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Tidskriftsartikel (refereegranskat)
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- Nyström, Helena Filipsson, 1966, et al.
(författare)
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Iodine status in the Nordic countries past and present
- 2016
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Ingår i: Food & Nutrition Research. - : SNF Swedish Nutrition Foundation. - 1654-6628 .- 1654-661X. ; 60
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Tidskriftsartikel (refereegranskat)abstract
- Background: Adequate iodine nutrition is dependent on ground water content, seafood, and, as many countries use iodized cow fodder, dairy products. In most countries, salt fortification programs are needed to assure adequate iodine intake. Objectives: The objectives are threefold: 1) to describe the past and present iodine situation in the Nordic countries, 2) to identify important gaps of knowledge, and 3) to highlight differences among the Nordic countries' iodine biomonitoring and fortification policies. Design: Historical data are compared with the current situation. The Nordic countries' strategies to achieve recommended intake and urine iodine levels and their respective success rates are evaluated. Results: In the past, the iodine situation ranged from excellent in Iceland to widespread goiter and cretinism in large areas of Sweden. The situation was less severe in Norway and Finland. According to a 1960 World Health Organization (WHO) report, there were then no observations of iodine deficiency in Denmark. In Sweden and Finland, the fortification of table salt was introduced 5075 years ago, and in Norway and Finland, the fortification of cow fodder starting in the 1950s helped improve the population's iodine status due to the high intake of milk. In Denmark, iodine has been added to household salt and salt in bread for the past 15 years. The Nordic countries differ with regard to regulations and degree of governmental involvement. There are indications that pregnant and lactating women, the two most vulnerable groups, are mildly deficient in iodine in several of the Nordic countries. Conclusion: The Nordic countries employ different strategies to attain adequate iodine nutrition. The situation is not optimal and is in need of re-evaluation. Iodine researchers, Nordic national food administrations, and Nordic governmental institutions would benefit from collaboration to attain a broader approach and guarantee good iodine health for all. © 2016 Helena Filipsson Nyström et al.
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- Wille-Jørgensen, P., et al.
(författare)
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An interim analysis of recruitment to the COLOFOL trial
- 2009
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Ingår i: Colorectal Disease. - : Wiley. - 1462-8910 .- 1463-1318. ; 10, s. 756-758
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: To analyse the ongoing process of recruiting patients into a multicenter randomized trial on follow-up after curative surgery for colorectal cancer. The trial is registered in Clinical Trials Registration. METHOD: Prospective registration of all operated patients as well as inclusions (curative resection, stage II or III disease, RESULTS: Between January 2006 and September 2007, 1309 patients have been operated upon. Of these 502 (38.3 %) met the inclusion criteria, 148 (29.5%) had exclusion criteria. Of the final eligible patients 241 (68.1%) were randomized. No specific barriers to inclusion were identified. CONCLUSION: Of an overall population of patients operated for colorectal cancer about one in five were randomized. Bearing the rigorous inclusion and exclusion criteria in mind, this is considered satisfactory, and the investigated population may be representative of patients meeting the inclusion criteria.
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| 36. |
- Willows, R D, et al.
(författare)
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Crystallization and preliminary X-ray analysis of the Rhodobacter capsulatus magnesium chelatase BchI subunit
- 1999
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Ingår i: Acta Crystallographica. Section D: Biological Crystallography. - 1399-0047. ; D55, s. 689-690
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Tidskriftsartikel (refereegranskat)abstract
- The Rhodobacter capsulatus BchI protein is one of three subunits of Mg chelatase, the enzyme which catalyzes the first committed step of chlorophyll and bacteriochlorophyll biosynthesis. The BchI protein was produced with an inducible T7 RNA polymerase expression system in Escherichia coli. The protein was purified from the soluble cell-extract fraction and crystallized from polyethylene glycol solution. The crystals diffract to a minimum Bragg spacing of 2.1 Å. The space group is P63 with unit-cell dimensions a = b = 90.6, c = 84.1 Å.
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