| 1. |
- Hedlund, Pe rOlov, et al.
(författare)
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Significance of pretreatment cardiovascular morbidity as a risk factor during treatment with parenteral oestrogen or combined androgen deprivation of 915 patients with metastasized prostate cancer: Evaluation of cardiovascular events in a randomized trial
- 2011
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Ingår i: Scandinavian Journal of Urology and Nephrology. - London : Informa Healthcare. - 0036-5599 .- 1651-2065. ; 45:5, s. 346-353
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Tidskriftsartikel (refereegranskat)abstract
- Objective. This study aimed to evaluate prognostic risk factors for cardiovascular events during treatment of metastatic prostate cancer patients with high-dose parenteral polyoestradiol phosphate (PEP, Estradurin (R)) or combined androgen deprivation (CAD) with special emphasis on pretreatment cardiovascular disease. Material and methods. Nine-hundred and fifteen patients with T0-4, Nx, M1, G1-3, hormone- naive prostate cancer were randomized to treatment with PEP 240 mg i.m. twice a month for 2 months and thereafter monthly, or to flutamide (Eulexin (R)) 250 mg per os three times daily in combination with either triptorelin (Decapeptyl (R)) 3.75 mg i.m. per month or on an optional basis with bilateral orchidectomy. Pretreatment cardiovascular morbidity was recorded and cardiovascular events during treatment were assessed by an experienced cardiologist. A multivariate analysis was done using logistic regression. Results. There was a significant increase in cardiovascular events during treatment with PEP in patients with previous ischaemic heart disease (p = 0.008), ischaemic cerebral disease (p = 0.002), intermittent claudication (p = 0.031) and especially when the whole group of patients with pretreatment cardiovascular diseases was analysed together (p andlt; 0.001). In this group 33% of the patients had a cardiovascular event during PEP treatment. In the multivariate analysis PEP stood out as the most important risk factor for cardiac complications (p = 0.029). Even in the CAD group there was a significant increase in cardiovascular events in the group with all previous cardiovascular diseases taken together (p = 0.036). Conclusions. Patients with previous cardiovascular disease are at considerable risk of cardiovascular events during treatment with high-dose PEP and even during CAD therapy. Patients without pretreatment cardiovascular morbidity have a moderate cardiovascular risk during PEP treatment and could be considered for this treatment if the advantages of this therapy, e. g. avoidance of osteopenia and hot flushes and the low price, are given priority.
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| 2. |
- Beer, Tomasz M, et al.
(författare)
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Enzalutamide in metastatic prostate cancer before chemotherapy
- 2014
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Ingår i: New England Journal of Medicine. - 0028-4793 .- 1533-4406. ; 371:5, s. 33-424
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Enzalutamide is an oral androgen-receptor inhibitor that prolongs survival in men with metastatic castration-resistant prostate cancer in whom the disease has progressed after chemotherapy. New treatment options are needed for patients with metastatic prostate cancer who have not received chemotherapy, in whom the disease has progressed despite androgen-deprivation therapy.METHODS: In this double-blind, phase 3 study, we randomly assigned 1717 patients to receive either enzalutamide (at a dose of 160 mg) or placebo once daily. The coprimary end points were radiographic progression-free survival and overall survival.RESULTS: The study was stopped after a planned interim analysis, conducted when 540 deaths had been reported, showed a benefit of the active treatment. The rate of radiographic progression-free survival at 12 months was 65% among patients treated with enzalutamide, as compared with 14% among patients receiving placebo (81% risk reduction; hazard ratio in the enzalutamide group, 0.19; 95% confidence interval [CI], 0.15 to 0.23; P<0.001). A total of 626 patients (72%) in the enzalutamide group, as compared with 532 patients (63%) in the placebo group, were alive at the data-cutoff date (29% reduction in the risk of death; hazard ratio, 0.71; 95% CI, 0.60 to 0.84; P<0.001). The benefit of enzalutamide was shown with respect to all secondary end points, including the time until the initiation of cytotoxic chemotherapy (hazard ratio, 0.35), the time until the first skeletal-related event (hazard ratio, 0.72), a complete or partial soft-tissue response (59% vs. 5%), the time until prostate-specific antigen (PSA) progression (hazard ratio, 0.17), and a rate of decline of at least 50% in PSA (78% vs. 3%) (P<0.001 for all comparisons). Fatigue and hypertension were the most common clinically relevant adverse events associated with enzalutamide treatment.CONCLUSIONS: Enzalutamide significantly decreased the risk of radiographic progression and death and delayed the initiation of chemotherapy in men with metastatic prostate cancer. (Funded by Medivation and Astellas Pharma; PREVAIL ClinicalTrials.gov number, NCT01212991.).
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| 3. |
- Tyrsted, Christoffer, et al.
(författare)
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In-Situ Synchrotron Radiation Study of Formation and Growth of Crystalline CexZr1-xO2 Nanoparticles Synthesized in Supercritical Water
- 2010
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Ingår i: Chemistry of Materials. - : American Chemical Society (ACS). - 0897-4756 .- 1520-5002. ; 22:5, s. 1814-1820
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Tidskriftsartikel (refereegranskat)abstract
- In situ synchrotron powder X-ray diffraction (PXRD) measurements have been conducted to follow the nucleation and growth of crystalline CexZr1-xO2 nanoparticles synthesized in supercritical water with a full substitution variation (x = 0, 0.2, 0.5, 0.8, and 1.0). Direction-dependent growth curves are determined and described using reaction kinetic models. A disctinct change in growth kinetics is observed with increasing cerium content. For x = 0.8 and 1.0 (high cerium content), the growth in initially limited by the surface reaction kinetics, however, at a size of similar to 6 nm, the growth changes and becomes limited by the diffusion of monomers toward the surface. For x = 0 and 0.2, the opposite behavior is observed with the growth initially being limited by diffusion (up to similar to 3.5 nm) and later by the surface reaction kinetics. Thus, although a continuous solid solution can be obtained for the ceria-zirconia system, the growth of ceria and zirconia nanoparticles is fundamentally different under supercritical flow reactor. The resulting samples were analyzed using PXRD, small-angle X-ray scattering (SAXS), and transmission electron microscopy (TEM). The nanoparticles with x = 0, 0.2, and 0.5 have very low polydispersities. The sizes range from 4 nm to 7 nm, and the particles exhibit a reversibly pH-dependent agglomeration.
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| 4. |
- Bianchi, Marco, et al.
(författare)
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Robust Surface Doping of Bi2Se3 by Rubidium Intercalation
- 2012
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Ingår i: ACS Nano. - : American Chemical Society (ACS). - 1936-086X .- 1936-0851. ; 6:8, s. 7009-7015
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Tidskriftsartikel (refereegranskat)abstract
- Rubidium adsorption on the surface of the topological insulator Bi2Se3 is found to induce a strong downward band bending, leading to the appearance of a quantum-confined two-dimensional electron gas state (2DEG) in the conduction band. The 2DEG shows a strong Rashba-type spin orbit splitting, and it has previously been pointed out that this has relevance to nanoscale spintronics devices. The adsorption of Rb atoms, on the other hand, renders the surface very reactive, and exposure to oxygen leads to a rapid degrading of the 2DEG. We show that intercalating the Rb atoms, presumably into the van der Waals gaps in the quintuple layer structure of Bi2Se3, drastically reduces the surface reactivity while not affecting the promising electronic structure. The intercalation process is observed above room temperature and accelerated with increasing initial Rb coverage, an effect that is ascribed to the Coulomb interaction between the charged Rb ions. Coulomb repulsion is also thought to be responsible for a uniform distribution of Rb on the surface.
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| 5. |
- Kulmala, M., et al.
(författare)
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General overview: European Integrated project on Aerosol Cloud Climate and Air Quality interactions (EUCAARI) - integrating aerosol research from nano to global scales
- 2011
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Ingår i: Atmospheric Chemistry And Physics. - : Copernicus GmbH. - 1680-7316 .- 1680-7324. ; 11:24, s. 13061-13143
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Tidskriftsartikel (refereegranskat)abstract
- In this paper we describe and summarize the main achievements of the European Aerosol Cloud Climate and Air Quality Interactions project (EUCAARI). EUCAARI started on 1 January 2007 and ended on 31 December 2010 leaving a rich legacy including: (a) a comprehensive database with a year of observations of the physical, chemical and optical properties of aerosol particles over Europe, (b) comprehensive aerosol measurements in four developing countries, (c) a database of airborne measurements of aerosols and clouds over Europe during May 2008, (d) comprehensive modeling tools to study aerosol processes fron nano to global scale and their effects on climate and air quality. In addition a new Pan-European aerosol emissions inventory was developed and evaluated, a new cluster spectrometer was built and tested in the field and several new aerosol parameterizations and computations modules for chemical transport and global climate models were developed and evaluated. These achievements and related studies have substantially improved our understanding and reduced the uncertainties of aerosol radiative forcing and air quality-climate interactions. The EUCAARI results can be utilized in European and global environmental policy to assess the aerosol impacts and the corresponding abatement strategies.
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| 6. |
- Larsen, Signe Benzon, et al.
(författare)
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Baseline prostate-specific antigen measurements and subsequent prostate cancer risk in the Danish Diet, Cancer and Health cohort
- 2013
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Ingår i: European Journal of Cancer. - : Elsevier BV. - 1879-0852 .- 0959-8049. ; 49:14, s. 3041-3048
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Tidskriftsartikel (refereegranskat)abstract
- Aim: Although prostate-specific antigen (PSA) screening reduces mortality from prostate cancer, substantial over-diagnosis and subsequent overtreatment are concerns. Early screening of men for PSA may serve to stratify the male population by risk of future clinical prostate cancer. Methods and material: Case-control study nested within the Danish 'Diet, Cancer and Health' cohort of 27,179 men aged 50-64 at enrolment. PSA measured in serum collected at cohort entry in 1993-1997 was used to evaluate prostate cancer risk diagnosed up to 14 years after. We identified 911 prostate cancer cases in the Danish Cancer Registry through 31st December 2007 1:1 age-matched with cancer-free controls. Aggressive cancer was defined as >= T3 or Gleason score >= 7 or N1 or M1. Statistical analyses were based on conditional logistic regression with age as underlying time axis. Results: Total PSA and free-to-total PSA ratio at baseline were strongly associated with prostate cancer risk up to 14 years later. PSA was grouped in quintiles and free-to-total PSA ratio divided in three risk groups. The incidence rate ratio for prostate cancer was 150 (95% confidence interval, 72-310) among men with a total PSA in the highest quintile (>5.1 ng/ml) compared to the lowest (<0.80 ng/ml). The risk of aggressive cancer was highly elevated in men with a PSA level in the highest quintile. The results indicate that one-time measurement of PSA could be used in an individualised screening strategy, sparing a large proportion of men from further PSA-based screening. (C) 2013 Elsevier Ltd. All rights reserved.
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| 7. |
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| 8. |
- Tibaek, Sigrid, et al.
(författare)
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Is well-being associated with lower urinary tract symptoms in patients with stroke?
- 2011
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Ingår i: Scandinavian Journal of Urology and Nephrology. - : Informa UK Limited. - 0036-5599 .- 1651-2065. ; 45:2, s. 134-142
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Tidskriftsartikel (refereegranskat)abstract
- Objective. This study aimed to assess self-reported well-being in a clinical sample of stroke patients and to identify possible associations with prevalence, severity and bother of lower urinary tract symptoms (LUTS). Material and methods. A cross-sectional, clinical survey was initiated whereby stroke patients were invited to complete The WHO-Five Well-Being Index (WHO-5) and a LUTS instrument, the Danish Prostatic Symptom Score (DAN-PSS-1) questionnaire. Of 519 stroke patients invited, 482 subjects were eligible and 407 (84%) respondents answered the questionnaires. Results. Poor well-being (sum score < 13) was reported by 22% of all stroke patients, for women 29% and for men 14%. Depression (sum score < 8) was reported by 10%, for women 11% and for men 8%. Poor well-being was significantly (p < 0.01) associated with severity and bother of LUTS. Likewise, poor well-being was significantly (p < 0.001) associated with the prevalence of four different symptom groups of LUTS. Conclusions. The results indicate that poor well-being is present in stroke patients with LUTS, especially in women. Likewise, the data showed significant association between poor well-being and LUTS. Screening for well-being and LUTS in stroke patients is strongly recommended.
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| 9. |
- Ulmert, David, et al.
(författare)
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Rapid elimination kinetics of free PSA or human kallikrein-related peptidase 2 after initiation of gonadotropin-releasing hormone-antagonist treatment of prostate cancer: potential for rapid monitoring of treatment responses
- 2012
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Ingår i: Clinical Chemistry and Laboratory Medicine. - : Walter de Gruyter GmbH. - 1434-6621 .- 1437-4331. ; 50:11, s. 1993-1998
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Tidskriftsartikel (refereegranskat)abstract
- Background: The utility of conventional prostate-specifi c antigen (PSA) measurements in blood for monitoring rapid responses to treatment for prostate cancer is limited because of its slow elimination rate. Prior studies have shown that free PSA (fPSA), intact PSA (iPSA) and human kallikrein-related peptidase 2 (hK2) are eliminated more rapidly after radical prostatectomy. In contrast, all three markers have similarly slow elimination rates after castration induced by gonadotropin-releasing hormone (GnRH) agonists, possibly due to the slow onset of castration. Therefore, we assessed elimination rates of tPSA, fPSA, iPSA and hK2 after rapid induction of castration with degarelix (Firmagon (R)), a novel GnRH antagonist. Methods: This study included 24 patients treated with degarelix. Blood was taken at 1, 3, 7, 14, 21 and 28 days after injection of degarelix. Free and total PSA were measured with a commercial dual-label assay, and with inhouse research assays of intact PSA and hK2. Results: Median (interquartile range, IQR) tPSA at baseline was 23.4 (15.8, 59.8). Twenty-two patients (92%) reached castrate levels of testosterone within 24 h of degarelix initiation, and all patients did so within 72 h. All kallikrein forms declined in an exponential fashion after degarelix administration. The median time to 50% reduction in biomarker level was 8-9 days for tPSA or complexed PSA vs. 2-4 days for hK2, iPSA and fPSA. The percentage eliminated at day 3 and day 7 was significantly higher for hK2, iPSA and fPSA than for tPSA (all p<0.02), while tPSA and complexed PSA were similar. Conclusions: The rapid decline of fPSA, iPSA and hK2 after fast induction of castration with degarelix is similar to that reported after prostatectomy and offers a novel, informative method to monitor rapid onset of therapeutic action targeting signaling of the androgen receptor.
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| 10. |
- van de Velde, Cornelis J. H., et al.
(författare)
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EURECCA colorectal : Multidisciplinary Mission statement on better care for patients with colon and rectal cancer in Europe
- 2013
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Ingår i: European Journal of Cancer. - : Elsevier BV. - 0959-8049 .- 1879-0852. ; 49:13, s. 2784-2790
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Tidskriftsartikel (refereegranskat)abstract
- Background: Care for patients with colon and rectal cancer has improved in the last twenty years however still considerable variation exists in cancer management and outcome between European countries. Therefore, EURECCA, which is the acronym of European Registration of cancer care, is aiming at defining core treatment strategies and developing a European audit structure in order to improve the quality of care for all patients with colon and rectal cancer. In December 2012 the first multidisciplinary consensus conference about colon and rectum was held looking for multidisciplinary consensus. The expert panel consisted of representatives of European scientific organisations involved in cancer care of patients with colon and rectal cancer and representatives of national colorectal registries.Methods: The expert panel had delegates of the European Society of Surgical Oncology (ESSO), European Society for Radiotherapy & Oncology (ESTRO), European Society of Pathology (ESP), European Society for Medical Oncology (ESMO), European Society of Radiology (ESR), European Society of Coloproctology (ESCP), European CanCer Organisation (ECCO), European Oncology Nursing Society (EONS) and the European Colorectal Cancer Patient Organisation (EuropaColon), as well as delegates from national registries or audits. Experts commented and voted on the two web-based online voting rounds before the meeting (between 4th and 25th October and between the 20th November and 3rd December 2012) as well as one online round after the meeting (4th-20th March 2013) and were invited to lecture on the subjects during the meeting (13th-15th December 2012). The sentences in the consensus document were available during the meeting and a televoting round during the conference by all participants was performed. All sentences that were voted on are available on the EURECCA website www.canceraudit.eu. The consensus document was divided in sections describing evidence based algorithms of diagnostics, pathology, surgery, medical oncology, radiotherapy, and follow-up where applicable for treatment of colon cancer, rectal cancer and stage IV separately. Consensus was achieved using the Delphi method.Results: The total number of the voted sentences was 465. All chapters were voted on by at least 75% of the experts. Of the 465 sentences, 84% achieved large consensus, 6% achieved moderate consensus, and 7% resulted in minimum consensus. Only 3% was disagreed by more than 50% of the members.Conclusions: It is feasible to achieve European Consensus on key diagnostic and treatment issues using the Delphi method. This consensus embodies the expertise of professionals from all disciplines involved in the care for patients with colon and rectal cancer. Diagnostic and treatment algorithms were developed to implement the current evidence and to define core treatment guidance for multidisciplinary team management of colon and rectal cancer throughout Europe.
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