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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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- Wille-Jorgensen, Peer, et al.
(författare)
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Effect of More vs Less Frequent Follow-up Testing on Overall and Colorectal Cancer-Specific Mortality in Patients With Stage II or III Colorectal Cancer The COLOFOL Randomized Clinical Trial
- 2018
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Ingår i: Journal of the American Medical Association (JAMA). - : AMER MEDICAL ASSOC. - 0098-7484 .- 1538-3598. ; 319:20, s. 2095-2103
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Tidskriftsartikel (refereegranskat)abstract
- IMPORTANCE Intensive follow-up of patients after curative surgery for colorectal cancer is common in clinical practice, but evidence of a survival benefit is limited.OBJECTIVE To examine overall mortality, colorectal cancer-specific mortality, and colorectal cancer-specific recurrence rates among patients with stage II or III colorectal cancer who were randomized after curative surgery to 2 alternative schedules for follow-up testing with computed tomography and carcinoembryonic antigen.DESIGN, SETTING, AND PARTICIPANTS Unblinded randomized trial including 2509 patients with stage II or III colorectal cancer treated at 24 centers in Sweden, Denmark, and Uruguay from January 2006 through December 2010 and followed up for 5 years; follow-up ended on December 31, 2015.INTERVENTIONS Patients were randomized either to follow-up testing with computed tomography of the thorax and abdomen and serum carcinoembryonic antigen at 6, 12, 18, 24, and 36 months after surgery (high-frequency group; n = 1253 patients) or at 12 and 36 months after surgery (low-frequency group; n = 1256 patients).MAIN OUTCOMES AND MEASURES The primary outcomes were 5-year overall mortality and colorectal cancer-specific mortality rates. The secondary outcome was the colorectal cancer-specific recurrence rate. Both intention-to-treat and per-protocol analyses were performed.RESULTS Among 2555 patients who were randomized, 2509 were included in the intention-to-treat analysis (mean age, 63.5 years; 1128 women [45%]) and 2365 (94.3%) completed the trial. The 5-year overall patient mortality rate in the high-frequency group was 13.0%(161/1253) compared with 14.1%(174/1256) in the low-frequency group (risk difference, 1.1% [95% CI, -1.6% to 3.8%]; P =.43). The 5-year colorectal cancer-specific mortality rate in the high-frequency group was 10.6%(128/1248) compared with 11.4%(137/1250) in the low-frequency group (risk difference, 0.8%[ 95% CI, -1.7% to 3.3%]; P =.52). The colorectal cancer-specific recurrence rate was 21.6%(265/1248) in the high-frequency group compared with 19.4%(238/1250) in the low-frequency group (risk difference, 2.2%[ 95% CI, -1.0% to 5.4%]; P =.15).CONCLUSIONS AND RELEVANCE Among patients with stage II or III colorectal cancer, follow-up testing with computed tomography and carcinoembryonic antigen more frequently compared with less frequently did not result in a significant rate reduction in 5-year overall mortality or colorectal cancer-specific mortality.
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- Cao, Christopher, et al.
(författare)
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Prospective Registry On Mesothelioma Peritonei Treatment (PROMPT) : study design and rationale
- 2012
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Ingår i: Tumori (Milano). - 0300-8916 .- 2038-2529. ; 98:1, s. 166-171
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Tidskriftsartikel (refereegranskat)abstract
- Diffuse malignant peritoneal mesothelioma (DMPM) is an aggressive and rare form of cancer arising from the mesothelial lining of the peritoneum. Due to the latency period between asbestos exposure and disease progression, the peak in incidence of DMPM is likely to occur in the coming decade for many industrialized nations, with a multitude of industrial, medico-legal and health-related implications(1,2). Traditional therapeutic modalities such as systemic chemotherapy and radiotherapy have not been proven to be effective in the treatment of DMPM, and patients diagnosed with the disease have a life expectancy of less than 12 months(3-5). Combined treatment involving cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) has been utilized in several specialized centers around the world and has been found to be a feasible procedure with encouraging survival outcomes(6-8).
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- Laurberg, M, et al.
(författare)
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Structure of a mutant EF-G reveals domain III and possibly the fusidic acid binding site
- 2000
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Ingår i: Journal of Molecular Biology. - : Elsevier BV. - 0022-2836 .- 1089-8638. ; 303:4, s. 593-603
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Tidskriftsartikel (refereegranskat)abstract
- The crystal structure of Thermus thermophilus elongation factor G (EF-G) carrying the point mutation His573Ala was determined at a resolution of 2.8 Å. The mutant has a more closed structure than that previouslyreported for wild-type EF-G. This is obtained by a 10° rigid rotation of domains III, IV and V with regardto domains I and II. This rotation results in a displacement of the tipof domain IV by approximately 9 Å. The structure of domain III is nowfully visible and reveals the double split β-α-β motif also observed for EF-G domain V and for several ribosomal proteins. A large number of fusidic acid resistant mutations found in domain III have now been possible tolocate. Possible locations for the effector loop and a possible bindingsite for fusidic acid are discussed in relation to some of the fusidic acid resistant mutations.
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- 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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