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| 2. |
- 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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- Madler, C.F., et al.
(författare)
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Non-invasive diagnosis of coronary artery disease by quantitative stress echocardiography : Optimal diagnostic models using off-line tissue Doppler in the MYDISE study
- 2003
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Ingår i: European Heart Journal. - 0195-668X .- 1522-9645. ; 24:17, s. 1584-1594
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Tidskriftsartikel (refereegranskat)abstract
- Aims: To develop optimal methods for the objective non-invasive diagnosis of coronary artery disease, using myocardial Doppler velocities during dobutamine stress echocardiography. Methods and results: We acquired tissue Doppler digital data during dobutamine stress in 289 subjects, and measured myocardial responses by off-line analysis of 11 left ventricular segments. Diagnostic criteria developed by comparing 92 normal subjects with 48 patients with coronary disease were refined in a prospective series of 149 patients referred with chest pain. Optimal diagnostic accuracy was achieved by logistic regression models, using systolic velocities at maximal stress in 7 myocardial segments, adjusting for independent correlations directly with heart rate and inversely with age and female gender (all p<0.001). Best cut-points from receiveroperator curves diagnosed left anterior descending, circumflex and right coronary disease with sensitivities and specificities of 80% and 80%, 91% and 80%, and 93% and 82%, respectively. All models performed better than velocity cut-offs alone (p<0.001). Conclusion: Non-invasive diagnosis of coronary artery disease by quantitative stress echocardiography is best performed using diagnostic models based on segmental velocities at peak stress and adjusting for heart rate, and gender or age. © 2003 Published by Elsevier Ltd on behalf of The European Society of Cardiology.
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| 4. |
- Ran, C., et al.
(författare)
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Strong association between glucocerebrosidase mutations and Parkinson's disease in Sweden
- 2016
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Ingår i: Neurobiology of Aging. - : Elsevier BV. - 0197-4580 .- 1558-1497. ; 45
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Tidskriftsartikel (refereegranskat)abstract
- Several genetic studies have demonstrated an association between mutations in glucocerebrosidase (GBA), originally implicated in Gaucher's disease, and an increased risk of Parkinson's disease (PD). We have investigated the possible involvement of genetic GBA variations in PD in the Swedish population. Three GBA variants, E326K, N370S, and L444P were screened in the largest Swedish Parkinson cohort reported to date; 1625 cases and 2025 control individuals. We found a significant association with high effect size of the rare variant L444P with PD (odds ratio 8.17; 95% confidence interval: 2.51-26.23; p-value = 0.0020) and a significant association of the common variant E326K (odds ratio 1.60; 95% confidence interval: 1.16-2.22; p-value = 0.026). The rare variant N370S showed a trend for association. Most L444P carriers (68%) were found to reside in northern Sweden, which is consistent with a higher prevalence of Gaucher's disease in this part of the country. Our findings support the role of GBA mutations as risk factors for PD and point to lysosomal dysfunction as a mechanism contributing to PD etiology. (C) 2016 The Author(s). Published by Elsevier Inc.
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| 6. |
- Hallqvist, Andreas, 1973, et al.
(författare)
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Concurrent cetuximab and radiotherapy after docetaxel-cisplatin induction chemotherapy in stage III NSCLC : Satellite-A phase II study from the Swedish Lung Cancer Study Group
- 2011
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Ingår i: Lung Cancer. - : Elsevier BV. - 0169-5002 .- 1872-8332. ; 71:2, s. 166-172
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Tidskriftsartikel (refereegranskat)abstract
- Background: Several attempts to increase the locoregional control in locally advanced lung cancer including concurrent chemotherapy, accelerated fractionation and dose escalation have been made during the last years. As the EGFR directed antibody cetuximab has shown activity concurrent with radiotherapy in squamous cell carcinoma of the head and neck, as well as in stage IV NSCLC combined with chemotherapy, we wanted to investigate radiotherapy with concurrent cetuximab in locally advanced NSCLC, a tumour type often over expressing the EGF-receptor. Methods: Between February 2006 and August 2007 75 patients in stage Ill NSCLC with good performance status (PS 0 or 1) and adequate lung function (FEV1 > 1.0) were enrolled in this phase II study at eight institutions. Treatment consisted of 2 cycles of induction chemotherapy, docetaxel 75 mg/m(2) and cisplatin 75 mg/m(2) with 3 weeks interval. An initial dose of cetuximab 400 mg/m(2) was given before start of 3D-CRT to 68 Gy with 2 Gy per fraction in 7 weeks concurrent with weekly cetuximab 250 mg/m(2). Toxicity was scored weekly during radiotherapy (CTC 3.0), and after treatment the patients were followed every third month with CT-scans, toxicity scoring and QLQ. Results: Seventy-one patients were eligible for analysis as four were incorrectly enrolled. Histology: adenocarcinoma 49%, squamous cell carcinoma 39% and other NSCLC 12%. The majority had PS 0 (62.5%), median age 62.2 (42-81), 50% were women and 37% had a pre-treatment weight loss > 5%. Toxicity: esophagitis grade 1-2: 72%; grade 3:1.4%. Hypersensitivity reactions grade 3-4: 5.6%. Febrile neutropenia grade 3-4: 15.4%. Skin reactions grade 1-2: 74%; grade 3: 4.2%. Diarrhoea grade 1-2: 38%; grade 3: 11.3%. Pneumonitis grade 1-2: 26.8%; grade 3: 4.2%; grade 5:1.4%. The median follow-up was 39 months for patients alive and the median survival was 17 months with a 1-, 2- and 3-year OS of 66%, 37% and 29% respectively. Until now local or regional failure has occurred in 20 patients and 22 patients have developed distant metastases. Weight loss, PS and stage were predictive for survival in univariate as well as in multivariate analysis. Conclusion: Induction chemotherapy followed by concurrent cetuximab and RT to 68 Gy is clearly feasible with promising survival. Toxicity, e.g. pneumonitis and esophagitis is low compared to most schedules with concurrent chemotherapy. This treatment strategy should be evaluated in a randomised manner vs. concurrent chemoradiotherapy to find out if it is a valid treatment option.
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| 7. |
- Janerot-Sjöberg, Birgitta, 1958-, et al.
(författare)
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Effect of contrast on systolic myocardial ultrasound color-Doppler velocity.
- 2001
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Ingår i: Proceedings to IEEE Engineering Med & Biol(CD skiva),2001. - : IEEE. - 0780372115 ; , s. 3289-3291
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Konferensbidrag (refereegranskat)abstract
- Intravenously distributed ultrasound contrast increases echoes from the normally low echogenic bloodpool and myocardial perfusion imaging is developing. However the microspheres used are potential endothelial stimulators as well as nonlinear scatterers. Tissue Doppler is developed to detect velocities of myocardial motion, which are in the same range as perfusion flow velocities. The effect of contrast is not evaluated. We performed echocardiography in 12 patients with ischemic heart disease before and immediately after a slow intravenous infusion of 27 ml Optison® using color myocardial Doppler imaging (GE Vingmed systemV). Longitudinal basal systolic velocities and their integrals were analyzed in digitally stored cineloops. Peak mean velocity increased 10% by contrast from mean 5.2 ± 1.8 (SD) to 5.7 ± 2.3 cm/s (p=0.02, confidence interval 2-16%) but integral did not change (0.8 ± 0.4 cm). Contrast has no effect on blood pressure or heart rate in used dose. It is therefore of interest to further evaluate if this increase in velocity; a) is a methodological effect that may be used to detect contrast within myocardium (and thereby perfusion/blood volume), or b) is secondary to increased flow and motion caused by endothelial and vascular effects from the contrast microspheres. Either have important methodological, physiological and clinical impact.
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| 8. |
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| 9. |
- Ressner, Marcus, 1967-, et al.
(författare)
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Effects of ultrasound contrast agents on Doppler tissue velocity estimation
- 2006
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Ingår i: Journal of the American Society of Echocardiography. - : Elsevier BV. - 0894-7317 .- 1097-6795. ; 19:2, s. 154-164
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Tidskriftsartikel (refereegranskat)abstract
- The combination of Doppler tissue imaging and myocardial contrast echocardiography has the potential to provide information about motion and perfusion of the myocardium in a single examination. The purpose of this study was to establish how the presence of ultrasound contrast agent (UCA) affects measurements of Doppler tissue velocities in vivo and in vitro. We performed echocardiography in 12 patients with ischemic heart disease before and immediately after a slow intravenous infusion of the UCA Optison, using color Doppler tissue imaging to examine the effect of contrast agents in vivo. The myocardial peak systolic velocities and their integrals were analyzed in digitally stored cineloops before and after contrast administration. To distinguish between methodologic and physiologic factors affecting the measurement of tissue velocity in vitro, experiments with a rotating disk and a flow cone phantom were also carried out for the 3 contrast agents: Optison, Sonovue, and Sonazoid. in vivo results show that the values for peak systolic velocity increased by about 10% during contrast infusion, from mean 5.2 +/- 1.8 to 5.7 +/- 2.3 cm/s (P = .02, 95% confidence interval 2%-16%). The increase in myocardial peak systolic velocities was verified in experimental models in which the UCA increased the estimated mean velocity in the order of 5% to 20% for the motion interval of 5 to 7 cm/s, corresponding to the myocardial velocities studied in vivo. The response was similar for all 3 contrast agents and was not affected by moderate variations in concentration of the agent. We have shown that the presence UCA will affect Doppler tissue measurements in vivo and in vitro. The observed bias is presumed to be an effect of harmonic signal contribution from rupturing contrast agent microbubbles and does not indicate biologic or physiologic effects.
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