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- Fullman, N., et al.
(författare)
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Measuring progress and projecting attainment on the basis of past trends of the health-related Sustainable Development Goals in 188 countries: an analysis from the Global Burden of Disease Study 2016
- 2017
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Ingår i: Lancet. - 0140-6736 .- 1474-547X. ; 390:10100, s. 1423-1459
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Tidskriftsartikel (refereegranskat)abstract
- Background The UN's Sustainable Development Goals (SDGs) are grounded in the global ambition of "leaving no one behind". Understanding today's gains and gaps for the health-related SDGs is essential for decision makers as they aim to improve the health of populations. As part of the Global Burden of Diseases, Injuries, and Risk Factors Study 2016 (GBD 2016), we measured 37 of the 50 health-related SDG indicators over the period 1990-2016 for 188 countries, and then on the basis of these past trends, we projected indicators to 2030. Methods We used standardised GBD 2016 methods to measure 37 health-related indicators from 1990 to 2016, an increase of four indicators since GBD 2015. We substantially revised the universal health coverage (UHC) measure, which focuses on coverage of essential health services, to also represent personal health-care access and quality for several non-communicable diseases. We transformed each indicator on a scale of 0-100, with 0 as the 2.5th percentile estimated between 1990 and 2030, and 100 as the 97.5th percentile during that time. An index representing all 37 health-related SDG indicators was constructed by taking the geometric mean of scaled indicators by target. On the basis of past trends, we produced projections of indicator values, using a weighted average of the indicator and country-specific annualised rates of change from 1990 to 2016 with weights for each annual rate of change based on out-of-sample validity. 24 of the currently measured health-related SDG indicators have defined SDG targets, against which we assessed attainment. Findings Globally, the median health-related SDG index was 56.7 (IQR 31.9-66.8) in 2016 and country-level performance markedly varied, with Singapore (86.8, 95% uncertainty interval 84.6-88.9), Iceland (86.0, 84.1-87.6), and Sweden (85.6, 81.8-87.8) having the highest levels in 2016 and Afghanistan (10.9, 9.6-11.9), the Central African Republic (11.0, 8.8-13.8), and Somalia (11.3, 9.5-13.1) recording the lowest. Between 2000 and 2016, notable improvements in the UHC index were achieved by several countries, including Cambodia, Rwanda, Equatorial Guinea, Laos, Turkey, and China; however, a number of countries, such as Lesotho and the Central African Republic, but also high-income countries, such as the USA, showed minimal gains. Based on projections of past trends, the median number of SDG targets attained in 2030 was five (IQR 2-8) of the 24 defined targets currently measured. Globally, projected target attainment considerably varied by SDG indicator, ranging from more than 60% of countries projected to reach targets for under-5 mortality, neonatal mortality, maternal mortality ratio, and malaria, to less than 5% of countries projected to achieve targets linked to 11 indicator targets, including those for childhood overweight, tuberculosis, and road injury mortality. For several of the health-related SDGs, meeting defined targets hinges upon substantially faster progress than what most countries have achieved in the past. Interpretation GBD 2016 provides an updated and expanded evidence base on where the world currently stands in terms of the health-related SDGs. Our improved measure of UHC offers a basis to monitor the expansion of health services necessary to meet the SDGs. Based on past rates of progress, many places are facing challenges in meeting defined health-related SDG targets, particularly among countries that are the worst off. In view of the early stages of SDG implementation, however, opportunity remains to take actions to accelerate progress, as shown by the catalytic effects of adopting the Millennium Development Goals after 2000. With the SDGs' broader, bolder development agenda, multisectoral commitments and investments are vital to make the health-related SDGs within reach of all populations. Copyright The Authors. Published by Elsevier Ltd. This is an Open Access article published under the CC BY 4.0 license.
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- Abe, O, et al.
(författare)
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Effects of chemotherapy and hormonal therapy for early breast cancer on recurrence and 15-year survival: an overview of the randomised trials
- 2005
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Ingår i: The Lancet. - 1474-547X. ; 365:9472, s. 1687-1717
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Tidskriftsartikel (refereegranskat)abstract
- Background Quinquennial overviews (1985-2000) of the randomised trials in early breast cancer have assessed the 5-year and 10-year effects of various systemic adjuvant therapies on breast cancer recurrence and survival. Here, we report the 10-year and 15-year effects. Methods Collaborative meta-analyses were undertaken of 194 unconfounded randomised trials of adjuvant chemotherapy or hormonal therapy that began by 1995. Many trials involved CMF (cyclophosphamide, methotrexate, fluorouracil), anthracycline-based combinations such as FAC (fluorouracil, doxombicin, cyclophosphamide) or FEC (fluorouracil, epirubicin, cyclophosphamide), tamoxifen, or ovarian suppression: none involved taxanes, trastuzumab, raloxifene, or modem aromatase inhibitors. Findings Allocation to about 6 months of anthracycline-based polychemotherapy (eg, with FAC or FEC) reduces the annual breast cancer death rate by about 38% (SE 5) for women younger than 50 years of age when diagnosed and by about 20% (SE 4) for those of age 50-69 years when diagnosed, largely irrespective of the use of tamoxifen and of oestrogen receptor (ER) status, nodal status, or other tumour characteristics. Such regimens are significantly (2p=0 . 0001 for recurrence, 2p<0 . 00001 for breast cancer mortality) more effective than CMF chemotherapy. Few women of age 70 years or older entered these chemotherapy trials. For ER-positive disease only, allocation to about 5 years of adjuvant tamoxifen reduces the annual breast cancer death rate by 31% (SE 3), largely irrespective of the use of chemotherapy and of age (<50, 50-69, &GE; 70 years), progesterone receptor status, or other tumour characteristics. 5 years is significantly (2p<0 . 00001 for recurrence, 2p=0 . 01 for breast cancer mortality) more effective than just 1-2 years of tamoxifen. For ER-positive tumours, the annual breast cancer mortality rates are similar during years 0-4 and 5-14, as are the proportional reductions in them by 5 years of tamoxifen, so the cumulative reduction in mortality is more than twice as big at 15 years as at 5 years after diagnosis. These results combine six meta-analyses: anthracycline-based versus no chemotherapy (8000 women); CMF-based versus no chemotherapy (14 000); anthracycline-based versus CMF-based chemotherapy (14 000); about 5 years of tamoxifen versus none (15 000); about 1-2 years of tamoxifen versus none (33 000); and about 5 years versus 1-2 years of tamoxifen (18 000). Finally, allocation to ovarian ablation or suppression (8000 women) also significantly reduces breast cancer mortality, but appears to do so only in the absence of other systemic treatments. For middle-aged women with ER-positive disease (the commonest type of breast cancer), the breast cancer mortality rate throughout the next 15 years would be approximately halved by 6 months of anthracycline-based chemotherapy (with a combination such as FAC or FEC) followed by 5 years of adjuvant tamoxifen. For, if mortality reductions of 38% (age <50 years) and 20% (age 50-69 years) from such chemotherapy were followed by a further reduction of 31% from tamoxifen in the risks that remain, the final mortality reductions would be 57% and 45%, respectively (and, the trial results could well have been somewhat stronger if there had been full compliance with the allocated treatments). Overall survival would be comparably improved, since these treatments have relatively small effects on mortality from the aggregate of all other causes. Interpretation Some of the widely practicable adjuvant drug treatments that were being tested in the 1980s, which substantially reduced 5-year recurrence rates (but had somewhat less effect on 5-year mortality rates), also substantially reduce 15-year mortality rates. Further improvements in long-term survival could well be available from newer drugs, or better use of older drugs.
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- Coombes, R C, et al.
(författare)
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Survival and safety of exemestane versus tamoxifen after 2-3 years' tamoxifen treatment (Intergroup Exemestane Study): a randomised controlled trial.
- 2007
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Ingår i: Lancet. - 1474-547X. ; 369:9561, s. 559-70
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Early improvements in disease-free survival have been noted when an aromatase inhibitor is given either instead of or sequentially after tamoxifen in postmenopausal women with oestrogen-receptor-positive early breast cancer. However, little information exists on the long-term effects of aromatase inhibitors after treatment, and whether these early improvements lead to real gains in survival. METHODS: 4724 postmenopausal patients with unilateral invasive, oestrogen-receptor-positive or oestrogen-receptor-unknown breast cancer who were disease-free on 2-3 years of tamoxifen, were randomly assigned to switch to exemestane (n=2352) or to continue tamoxifen (n=2372) for the remainder of a 5-year endocrine treatment period. The primary endpoint was disease-free survival; overall survival was a secondary endpoint. Efficacy analyses were intention-to-treat. This study is registered as an International Standard Randomised Controlled Trial, number ISRCTN11883920. RESULTS: After a median follow-up of 55.7 months (range 0-89.7), 809 events contributing to the analysis of disease-free survival had been reported (354 exemestane, 455 tamoxifen); unadjusted hazard ratio 0.76 (95% CI 0.66-0.88, p=0.0001) in favour of exemestane, absolute benefit 3.3% (95% CI 1.6-4.9) by end of treatment (ie, 2.5 years after randomisation). 222 deaths occurred in the exemestane group compared with 261 deaths in the tamoxifen group; unadjusted hazard ratio 0.85 (95% CI 0.71-1.02, p=0.08), 0.83 (0.69-1.00, p=0.05) when 122 patients with oestrogen-receptor-negative disease were excluded. CONCLUSIONS: Our results suggest that early improvements in disease-free survival noted in patients who switch to exemestane after 2-3 years on tamoxifen persist after treatment, and translate into a modest improvement in overall survival.
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| 18. |
- Gyllenberg, A, et al.
(författare)
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Variability in the CIITA gene interacts with HLA in multiple sclerosis.
- 2014
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Ingår i: Genes and immunity. - Stockholm : Springer Science and Business Media LLC. - 1476-5470 .- 1466-4879. ; 15, s. 162-167
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Tidskriftsartikel (refereegranskat)abstract
- The human leukocyte antigen (HLA) is the main genetic determinant of multiple sclerosis (MS) risk. Within the HLA, the class II HLA-DRB1*15:01 allele exerts a disease-promoting effect, whereas the class I HLA-A*02 allele is protective. The CIITA gene is crucial for expression of class II HLA molecules and has previously been found to associate with several autoimmune diseases, including MS and type 1 diabetes. We here performed association analyses with CIITA in 2000 MS cases and up to 6900 controls as well as interaction analysis with HLA. We find that the previously investigated single-nucleotide polymorphism rs4774 is associated with MS risk in cases carrying the HLA-DRB1*15 allele (P=0.01, odds ratio (OR): 1.21, 95% confidence interval (CI): 1.04-1.40) or the HLA-A*02 allele (P=0.01, OR: 1.33, 95% CI: 1.07-1.64) and that these associations are independent of the adjacent confirmed MS susceptibility gene CLEC16A. We also confirm interaction between rs4774 and HLA-DRB1*15:01 such that individuals carrying the risk allele for rs4774 and HLA-DRB1*15:01 have a higher than expected risk for MS. In conclusion, our findings support previous data that variability in the CIITA gene affects MS risk, but also that the effect is modulated by MS-associated HLA haplotypes. These findings further underscore the biological importance of HLA for MS risk.Genes and Immunity advance online publication, 16 January 2014; doi:10.1038/gene.2013.71.
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| 19. |
- Shin, J. H., et al.
(författare)
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IA-2 autoantibodies in incident type I diabetes patients are associated with a polyadenylation signal polymorphism in GIMAP5
- 2007
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Ingår i: Genes Immun. - : Springer Science and Business Media LLC. - 1466-4879 .- 1476-5470. ; 8:6, s. 503-12
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Tidskriftsartikel (refereegranskat)abstract
- In a large case-control study of Swedish incident type I diabetes patients and controls, 0-34 years of age, we tested the hypothesis that the GIMAP5 gene, a key genetic factor for lymphopenia in spontaneous BioBreeding rat diabetes, is associated with type I diabetes; with islet autoantibodies in incident type I diabetes patients or with age at clinical onset in incident type I diabetes patients. Initial scans of allelic association were followed by more detailed logistic regression modeling that adjusted for known type I diabetes risk factors and potential confounding variables. The single nucleotide polymorphism (SNP) rs6598, located in a polyadenylation signal of GIMAP5, was associated with the presence of significant levels of IA-2 autoantibodies in the type I diabetes patients. Patients with the minor allele A of rs6598 had an increased prevalence of IA-2 autoantibody levels compared to patients without the minor allele (OR=2.2; Bonferroni-corrected P=0.003), after adjusting for age at clinical onset (P=8.0 x 10(-13)) and the numbers of HLA-DQ A1*0501-B1*0201 haplotypes (P=2.4 x 10(-5)) and DQ A1*0301-B1*0302 haplotypes (P=0.002). GIMAP5 polymorphism was not associated with type I diabetes or with GAD65 or insulin autoantibodies, ICA, or age at clinical onset in patients. These data suggest that the GIMAP5 gene is associated with islet autoimmunity in type I diabetes and add to recent findings implicating the same SNP in another autoimmune disease.
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- Budde, U, et al.
(författare)
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Detailed von Willebrand factor multimer analysis in patients with von Willebrand disease in the European study, molecular and clinical markers for the diagnosis and management of type 1 von Willebrand disease (MCMDM-1VWD)
- 2008
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Ingår i: Journal of Thrombosis and Haemostasis. - : Elsevier BV. - 1538-7933 .- 1538-7836. ; 6:5, s. 762-771
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Tidskriftsartikel (refereegranskat)abstract
- Background: Type 1 von Willebrand disease (VWD) is a congenital bleeding disorder characterized by a partial quantitative deficiency of plasma von Willebrand factor (VWF) in the absence of structural and/or functional VWF defects. Accurate assessment of the quantity and quality of plasma VWF is difficult but is a prerequisite for correct classification. Objective: To evaluate the proportion of misclassification of patients historically diagnosed with type 1 VWD using detailed analysis of the VWF multimer structure. Patients and methods: Previously diagnosed type 1 VWD families and healthy controls were recruited by 12 expert centers in nine European countries. Phenotypic characterization comprised plasma VWF parameters and multimer analysis using low- and intermediate-resolution gels combined with an optimized visualization system. VWF genotyping was performed in all index cases (ICs). Results: Abnormal multimers were present in 57 out of 150 ICs; however, only 29 out of these 57 (51%) had VWF ristocetin cofactor to antigen ratio below 0.7. In most cases multimer abnormalities were subtle, and only two cases had a significant loss of the largest multimers. Conclusions: Of the cases previously diagnosed as type 1 VWD, 38% showed abnormal multimers. Depending on the classification criteria used, 22 out of these 57 cases (15% of the total cohort) may be reclassified as type 2, emphasizing the requirement for multimer analysis compared with a mere ratio of VWF functional parameters and VWF:Ag. This is further supported by the finding that even slightly aberrant multimers are highly predictive for the presence of VWF mutations.
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| 26. |
- Calon, T. G. A., et al.
(författare)
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Minimally Invasive Ponto Surgery Versus the Linear Incision Technique With Soft Tissue Preservation for Bone Conduction Hearing Implants: A Multicenter Randomized Controlled Trial
- 2018
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Ingår i: Otology & Neurotology. - : Ovid Technologies (Wolters Kluwer Health). - 1531-7129 .- 1537-4505. ; 39:7, s. 882-893
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Tidskriftsartikel (refereegranskat)abstract
- Objective:To compare the surgical outcomes of the Minimally Invasive Ponto Surgery (MIPS) technique with those of the linear incision technique with soft-tissue preservation for bone-anchored hearing systems (BAHS).Design:Sponsor-initiated multicenter, open, randomized, controlled clinical trial.Setting:Maastricht University Medical Centre, Ziekenhuisgroep Twente and Medisch Centrum Leeuwarden, all situated in The Netherlands.Participants:Sixty-four adult patients eligible for unilateral BAHS surgery.Interventions Single-stage BAHS surgery with 1:1 randomization to the linear incision technique with soft-tissue preservation (control) or the MIPS (test) group.Primary and Secondary Outcome Measurements:Primary objective: compare the incidence of inflammation (Holgers Index 2) during 12 weeks' follow-up after surgery. Secondary objectives: skin dehiscence, pain scores, loss of sensibility around the implant, soft-tissue overgrowth, skin sagging, implant extrusion, cosmetic results, surgical time, wound healing and Implant Stability Quotient measurements.Results:Sixty-three subjects were analyzed in the intention-to-treat population. No significant difference was found for the incidence of inflammation between groups. Loss of skin sensibility, cosmetic outcomes, skin sagging, and surgical time were significantly better in the test group. No statistically significant differences were found for dehiscence, pain, and soft-tissue overgrowth. A nonsignificant difference in extrusion was found for the test group. The Implant Stability Quotient was statistically influenced by the surgical technique, abutment length, and time.Conclusion:No significant differences between the MIPS and the linear incision techniques were observed regarding skin inflammation. MIPS results in a statistically significant reduction in the loss of skin sensibility, less skin sagging, improved cosmetic results, and reduced surgical time. Although nonsignificant, the implant extrusion rate warrants further research.
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| 27. |
- Christlieb, N., et al.
(författare)
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The Hamburg/ESO R-process Enhanced Star survey (HERES). I. Project description, and discovery of two stars with strong enhancements of neutron-capture elements
- 2004
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Ingår i: Astronomy & Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 428:3, s. 1027-1037
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Tidskriftsartikel (refereegranskat)abstract
- We report on a dedicated effort to identify and study metal-poor stars strongly enhanced in r-process elements ([r/Fe]>1 dex; hereafter r-IIstars), the Hamburg/ESO R-process Enhanced Star survey (HERES).Moderate-resolution (∼2 Å) follow-up spectroscopy has been obtained for metal-poor giant candidates selected from the Hamburg/ESO objective-prism survey (HES) as well as the HK survey to identify sharp-lined stars with [Fe/H]<-2.5 dex. For several hundred confirmed metal-poor giants brighter than B∼ 16.5 mag (most of them from theHES), ``snapshot'' spectra (R∼ 20 000; S/N ∼ 30 per pixel) are being obtained with VLT/UVES, with the main aim of finding the 2-3% r-II stars expected to be among them. These are studied in detail by means of higher resolution and higher S/N spectra. In this paper we describe a pilot study based on a set of 35 stars, including 23 from the HK survey,eight from the HES, and four comparison stars. We discovered two new r-II stars, CS 29497-004 ([Eu/Fe]=1.64± 0.22) and CS 29491-069([Eu/Fe]=1.08± 0.23). A first abundance analysis of CS 29497-004 yields that its abundances of Ba to Dy are on average enhanced by 1.5 dex with respect to iron and the Sun and match a scaled solar r-process pattern well, while Th is underabundant relative to that pattern by 0.3dex, which we attribute to radioactive decay. That is, CS 29497-004 seems not to belong to the class of r-process enhanced stars displaying an ``actinide boost'', like CS 31082-001 (Hill et al. 2002), or CS30306-132 (Honda et al. 2004b). The abundance pattern agrees well with predictions of the phenomenological model of Qian & Wasserburg.Based in large part on observations collected at the European Southern Observatory, Paranal, Chile (proposal number 68.B-0320).}
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| 28. |
- Eikenboom, J, et al.
(författare)
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Linkage analysis in families diagnosed with type 1 von Willebrand disease in the European study, molecular and clinical markers for the diagnosis and management of type 1 VWD
- 2006
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Ingår i: Journal of Thrombosis and Haemostasis. - : Elsevier BV. - 1538-7933 .- 1538-7836. ; 4:4, s. 774-782
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Tidskriftsartikel (refereegranskat)abstract
- Background: von Willebrand disease (VWD) type 1 is a congenital bleeding disorder caused by genetic defects in the von Willebrand factor (VWF) gene and characterized by a reduction of structurally normal VWF. The diagnosis of type 1 VWD is difficult because of clinical and laboratory variability. Furthermore, inconsistency of linkage between type 1 VWD and the VWF locus has been reported. Objectives: To estimate the proportion of type 1 VWD that is linked to the VWF gene. Patients and methods: Type 1 VWD families and healthy control individuals were recruited. An extensive questionnaire on bleeding symptoms was completed and phenotypic tests were performed. Linkage between VWF gene haplotypes and the diagnosis of type 1 VWD, the plasma levels of VWF and the severity of bleeding symptoms was analyzed. Results: Segregation analysis in 143 families diagnosed with type 1 VWD fitted a model of autosomal dominant inheritance. Linkage analysis under heterogeneity resulted in a summed lod score of 23.2 with an estimated proportion of linkage of 0.70. After exclusion of families with abnormal multimer patterns the linkage proportion was 0.46. LOD scores and linkage proportions were higher in families with more severe phenotypes and with phenotypes suggestive of qualitative VWF defects. About 40% of the total variation of VWF antigen could be attributed to the VWF gene. Conclusions: We conclude that the diagnosis of type 1 VWD is linked to the VWF gene in about 70% of families, however after exclusion of qualitative defects this is about 50%.
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| 31. |
- Sadler, J. E., et al.
(författare)
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Update on the pathophysiology and classification of von Willebrand disease: a report of the Subcommittee on von Willebrand Factor
- 2006
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Ingår i: Journal of Thrombosis and Haemostasis. - : Elsevier BV. - 1538-7933 .- 1538-7836. ; 4:10, s. 2103-2114
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Forskningsöversikt (refereegranskat)abstract
- von Willebrand disease (VWD) is a bleeding disorder caused by inherited defects in the concentration, structure, or function of von Willebrand factor (VWF). VWD is classified into three primary categories. Type 1 includes partial quantitative deficiency, type 2 includes qualitative defects, and type 3 includes virtually complete deficiency of VWF. VWD type 2 is divided into four secondary categories. Type 2A includes variants with decreased platelet adhesion caused by selective deficiency of high-molecular-weight VWF multimers. Type 2B includes variants with increased affinity for platelet glycoprotein Ib. Type 2M includes variants with markedly defective platelet adhesion despite a relatively normal size distribution of VWF multimers. Type 2N includes variants with markedly decreased affinity for factor VIII. These six categories of VWD correlate with important clinical features and therapeutic requirements. Some VWF gene mutations, alone or in combination, have complex effects and give rise to mixed VWD phenotypes. Certain VWD types, especially type 1 and type 2A, encompass several pathophysiologic mechanisms that sometimes can be distinguished by appropriate laboratory studies. The clinical significance of this heterogeneity is under investigation, which may support further subdivision of VWD type 1 or type 2A in the future.
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| 32. |
- Tosetto, A, et al.
(författare)
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A quantitative analysis of bleeding symptoms in type 1 von Willebrand disease: results from a multicenter European study (MCMDM-1 VWD)
- 2006
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Ingår i: Journal of Thrombosis and Haemostasis. - : Elsevier BV. - 1538-7933 .- 1538-7836. ; 4:4, s. 766-773
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Tidskriftsartikel (refereegranskat)abstract
- Background: A quantitative description of bleeding symptoms in type 1 von Willebrand disease (VWD) has never been reported. Objectives: The aim was to quantitatively evaluate the severity of bleeding symptoms in type 1 VWD and its correlation with clinical and laboratory features. Patients and methods: Bleeding symptoms were retrospectively recorded in a European cohort of VWD type 1 families, and for each subject a quantitative bleeding score (BS) was obtained together with phenotypic tests. Results: A total of 712 subjects belonging to 144 families and 195 controls were available for analysis. The BS was higher in index cases than in affected family members (BS 9 vs. 5, P < 0.0001) and in unaffected family members than in controls (BS 0 vs. -1, P < 0.0001). There was no effect of ABO blood group. BS showed a strong significant inverse relation with either von Willebrand ristocetin cofactor (VWF:RCo), von Willebrand antigen (VWF:Ag) or factor VIII procoagulant activity (FVIII:C) measured at time of enrollment, even after adjustment for age, sex and blood group (P < 0.001 for all the four upper quintiles of BS vs. the first quintile, for either VWF:RCo, VWF:Ag or FVIII:C). Higher BS was related with increasing likelihood of VWD, and a mucocutaneous BS (computed from spontaneous, mucocutaneous symptoms) was strongly associated with bleeding after surgery or tooth extraction. Conclusions: Quantitative analysis of bleeding symptoms is potentially useful for a more accurate diagnosis of type 1 VWD and to develop guidelines for its optimal treatment.
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| 33. |
- Tosetto, A., et al.
(författare)
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Impact of plasma von Willebrand factor levels in the diagnosis of type 1 von Willebrand disease: results from a multicenter European study (MCMDM-1VWD)
- 2007
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Ingår i: Journal of Thrombosis and Haemostasis. - : Elsevier BV. - 1538-7933 .- 1538-7836. ; 5:4, s. 715-721
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Tidskriftsartikel (refereegranskat)abstract
- Background: Presence of bleeding symptoms, inheritance and reduced von Willebrand factor (VWF) contribute to the diagnosis of type 1 von Willebrand disease (VWD). However, quantitative analysis of the importance of VWF antigen (VWF:Ag) and ristocetin cofactor activity (VWF:RCo) levels in the diagnosis is lacking. Objectives: To evaluate the relative contribution of VWF measurement to the diagnosis of VWD. Patients and methods: From the MCMDM-1VWD study cohort, 204 subjects (considered as affected by VWD based on the enrolling Center diagnoses and the presence of linkage with the VWF locus) were compared with 1155 normal individuals. Sensitivity, specificity and diagnostic positive likelihood ratios (LR) of VWF:Ag and VWF:RCo were computed. Results: ABO blood group was the variable most influencing VWF levels, but adjustment of the lower reference limit for the ABO group did not improve sensitivity and specificity of VWF:Ag or VWF:RCo. The lower reference limit (2.5th percentile) was 47 IU dL(-1) for both VWF:Ag and VWF:RCo and showed similar diagnostic performance [receiver-operator curve area: 0.962 and 0.961 for VWF:Ag and VWF:RCo, respectively; P = 0.81]. The probability of VWD was markedly increased only for values below 40 IU dL(-1) (positive LR: 95.1 for VWF:Ag), whereas intermediate values (40 to 60 IU dL(-1)) of VWF only marginally indicated the probability of VWD. Conclusions: Although the conventional 2.5 lower percentile has good sensitivity and specificity, only VWF:Ag or VWF:RCo values below 40 IU dL(-1) appear to significantly indicate the likelihood of type 1 VWD. The LR profile of VWF level could be used in a diagnostic algorithm.
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| 35. |
- Edberg, Niklas J. T., et al.
(författare)
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Effects of Saturn's magnetospheric dynamics on Titan's ionosphere
- 2015
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Ingår i: Journal of Geophysical Research - Space Physics. - 2169-9380 .- 2169-9402. ; 120:10, s. 8884-8898
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Tidskriftsartikel (refereegranskat)abstract
- We use the Cassini Radio and Plasma Wave Science/Langmuir probe measurements of the electron density from the first 110 flybys of Titan to study how Saturn's magnetosphere influences Titan's ionosphere. The data is first corrected for biased sampling due to varying solar zenith angle and solar energy flux (solar cycle effects). We then present results showing that the electron density in Titan's ionosphere, in the altitude range 1600-2400km, is increased by about a factor of 2.5 when Titan is located on the nightside of Saturn (Saturn local time (SLT) 21-03h) compared to when on the dayside (SLT 09-15 h). For lower altitudes (1100-1600km) the main dividing factor for the ionospheric density is the ambient magnetospheric conditions. When Titan is located in the magnetospheric current sheet, the electron density in Titan's ionosphere is about a factor of 1.4 higher compared to when Titan is located in the magnetospheric lobes. The factor of 1.4 increase in between sheet and lobe flybys is interpreted as an effect of increased particle impact ionization from approximate to 200eV sheet electrons. The factor of 2.5 increase in electron density between flybys on Saturn's nightside and dayside is suggested to be an effect of the pressure balance between thermal plus magnetic pressure in Titan's ionosphere against the dynamic pressure and energetic particle pressure in Saturn's magnetosphere.
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| 39. |
- Sandblom, G, et al.
(författare)
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Prostate-specific antigen as surrogate for characterizing prostate cancer subgroups
- 2002
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Ingår i: Scandinavian Journal of Urology and Nephrology. - : Informa UK Limited. - 0036-5599 .- 1651-2065. ; 36:2, s. 106-112
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE To evaluate how serum prostate-specific antigen (PSA) levels in a population-based cohort of men with prostate cancer vary with age and intensity in the diagnostic activity and to describe the treatment selection processes associated with PSA level. MATERIAL AND METHODS All men in the Swedish National Prostate Cancer Register diagnosed during 1996-1997 were included. In 1996 the register included 19 counties, covering 61% of the Swedish male population, and in 1997 21 counties with 79% of the Swedish male population. RESULTS A total of 8328 men were registered. PSA levels were missing in 341 cases. With increasing PSA there was a shift towards more advanced and poorly differentiated tumours. PSA at diagnosis increased with age, with the exception of patients younger than 50 years who had higher PSA values. The mean logarithm of PSA correlated negatively with the percentage of localized tumours (p < 0.005) and the age-adjusted incidence (p < 0.05) in each respective county in 1997. PSA was higher in men receiving radiotherapy compared with those treated with radical prostatectomy as well as in the group treated with bilateral orchiectomy compared with those receiving GnRH-analogues. CONCLUSIONS If PSA is used as a surrogate measure of extent of tumour volume in a population of prostate cancer patients, our findings indicate that age distribution and differences in incidence (possibly due to variation in diagnostic activity) should be taken into account. In our cohort there was a selection process, probably in part guided by PSA level, when choosing type of curative or palliative treatment.
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| 40. |
- Sandblom, G, et al.
(författare)
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Prostate-Specific Antigen for Prostate Cancer Staging in a Population-based Register
- 2002
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Ingår i: Scandinavian Journal of Urology and Nephrology. - : Informa UK Limited. - 0036-5599 .- 1651-2065. ; 36:2, s. 99-105
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Tidskriftsartikel (refereegranskat)abstract
- Objective: Previous studies have shown a relationship between serum prostate-specific antigen (PSA) level and prostate tumour volume. Reports based on selected case series have also indicated that serum PSA may be used for staging, although a varying prevalence of metastasizing tumours complicates the interpretation of these studies. In order to determine the accuracy of the serum level of PSA in predicting the presence of metastases we performed a prospective cohort study of a geographically defined population of men with prostate cancer.Methods: Serum level of PSA and the results of investigations for regional lymph node and distant metastases were recorded for all 8328 men with prostate cancer registered in the Swedish National Prostate Cancer Register 1996-1997.Results: The prevalence of lymph node metastases among men who had undergone lymph node exploration was 4%, 16% and 33% for well, moderately and poorly differentiated tumours. The corresponding prevalence of distant metastases was 12%, 30% and 48%. With serum PSA <20 ng/ml as a cut-off point the negative likelihood ratios for well and moderately differentiated tumours were found to be 0.47 and 0.45 for lymph node metastases and 0.24 and 0.18 for distant metastases, resulting in post-test probabilities >92% for the exclusion of metastases. In men with poorly differentiated tumours, the negative likelihood ratio would need to be even lower to safely exclude disseminated disease.Conclusion: For well to moderately differentiated tumours, further investigations to assess the presence of metastases may be omitted with no great risk for understaging if serum PSA <20 ng/ml.
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| 41. |
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| 42. |
- Andersson, Charlotte I J, et al.
(författare)
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Error-prone PCR of Vitreoscilla hemoglobin (VHb) to support the growth of microaerobic Escherichia coli
- 2000
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Ingår i: Biotechnology and Bioengineering. - 0006-3592. ; 70:4, s. 55-446
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Tidskriftsartikel (refereegranskat)abstract
- Expression of the gene encoding bacterial hemoglobin (VHb) from Vitreoscilla has been previously used to improve recombinant cell growth and enhance product formation under microaerobic conditions. It is very likely that the properties of VHb are not optimized for foreign hosts; therefore, we used error-prone PCR to generate a number of randomly mutated vhb genes to be expressed and studied in Escherichia coli. In addition, the mutated VHb proteins also contained an extension of eight residues (MTMITPSF) at the amino terminus. VHb mutants were screened for improved growth properties under microaerobic conditions and 15 clones expressing mutated hemoglobin protein were selected for further characterization and cultivated in a microaerobic bioreactor to analyze the physiological effects of novel VHb proteins on cell growth. The expression of four VHb mutants, carried by pVM20, pVM50, pVM104, and pVM134, were able to enhance microaerobic growth of E. coli by approximately 22%, 155%, 50%, and 90%, respectively, with a concomitant decrease of acetate excretion into the culture medium. The vhb gene in pVM20 contains two mutations substituting residues Glu19(A17) and Glu137(H23) to Gly. pVM50 expresses a VHb protein carrying two mutations: His36(C1) to Arg36 and Gln66(E20) to Arg66. pVM104 and pVM134 express VHb proteins carrying the mutations Ala56(E10) to Gly and Ile24(B5) to Thr, respectively. Our experiments also indicate that the positive effects elicited by mutant VHb-expression from pVM20 and pVM50 are linked to the peptide tail. Removal of the N-terminal sequence reduced cell growth approximately 23% and 53%, respectively, relative to wild-type controls. These results clearly demonstrate that it is possible to obtain mutated VHb proteins with improved characteristics for improving microaerobic growth of E. coli by using combined mutation techniques, addition of a peptide tail, and random error-prone PCR.
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| 43. |
- Andersson, J., et al.
(författare)
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Worse survival for TP53 (p53)-mutated breast cancer patients receiving adjuvant CMF
- 2005
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Ingår i: Ann Oncol. - : Elsevier BV. - 0923-7534 .- 1569-8041. ; 16:5, s. 743-8
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: TP53 has been described as a prognostic factor in many malignancies, including breast cancer. Whether it also might be a predictive factor with reference to chemo- and endocrine therapy is more controversial. PATIENTS AND METHODS: We investigated relapse-free (RFS), breast cancer-corrected (BCCS) and overall survival (OS) related to TP53 status in node-positive breast cancer patients that had received polychemotherapy [cyclophosphamide, methotrexate, 5-fluorouracil (CMF)] and/or endocrine therapy (tamoxifen). Sequence analyses of the whole TP53 coding region was performed in 376 patients operated on for primary breast cancer with axillary lymph node metastases between 1984 and 1989 (median follow-up time 84 months). RESULTS: TP53 mutations were found in 105 patients (28%). We found 90 (82%) of the 110 mutations in the more frequently analysed exons 5-8, while the other 20 (18%) were located in exons 3-4 and 9-10, respectively. Univariate analyses showed TP53 to be a significant prognostic factor with regard to RFS, BCCS and OS in patients who received adjuvant CMF. CONCLUSIONS: TP53 mutations might induce resistance to certain modalities of breast cancer therapy. Sequence-determined TP53 mutation was of negative prognostic value in the total patient population and in the CMF treated patients.
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| 44. |
- Astermark, J., et al.
(författare)
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Symposium in memory of Professor Inga Marie Nilsson
- 2001
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Ingår i: Haemophilia. - : Wiley. - 1351-8216. ; 7:4, s. 401-410
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Konferensbidrag (refereegranskat)abstract
- Professor Inga Marie Nilsson (1923-99) was a pioneer in the field of bleeding and thrombo-embolic disorders and made several major scientific contributions during her career. To honour her memory, colleagues from all over the world were invited to cover several aspects of haemostasis by giving state-of-the-art lectures at an international symposium in Malmö on September 22-23, 2000, chaired by Professors Lou Aledort and Erik Berntorp. Colleagues of Professor Nilsson in Malmö gave a short introduction to each topic. A short review of the meeting will be presented.
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| 45. |
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| 46. |
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| 47. |
- Calbet, J. A. L., et al.
(författare)
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A time-efficient reduction of fat mass in 4 days with exercise and caloric restriction
- 2015
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Ingår i: Scandinavian Journal of Medicine and Science in Sports. - : Wiley. - 0905-7188 .- 1600-0838. ; 25:2, s. 223-233
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Tidskriftsartikel (refereegranskat)abstract
- To determine whether a fast reduction in fat mass can be achieved in 4 days by combining caloric restriction (CR: 3.2kcal/kg body weight per day) with exercise (8-h walking+45-min arm cranking per day) to induce an energy deficit of approximate to 5000kcal/day, 15 overweight men underwent five experimental phases: pretest, exercise+CR for 4 days (WCR), control diet+reduced exercise for 3 days (DIET), and follow-up 4 weeks (POST1) and 1 year later (POST2). During WCR, the diet consisted solely of whey protein (n=8) or sucrose (n=7) (0.8g/kg body weight per day). After WCR, DIET, POST1, and POST2, fat mass was reduced by a mean of 2.1, 2.8, 3.8, and 1.9kg (P<0.05), with two thirds of this loss from the trunk; and lean mass by 2.8, 1.0, 0.5, and 0.4kg, respectively. After WCR, serum glucose, insulin, homeostatic model assessment, total and low-density lipoprotein cholesterol and triglycerides were reduced, and free fatty acid and cortisol increased. Serum leptin was reduced by 64%, 50%, and 33% following WCR, DIET, and POST1, respectively (P<0.05). The effects were similar in both groups. In conclusion, a clinically relevant reduction in fat mass can be achieved in overweight men in just 4 days by combining prolonged exercise with CR.
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| 48. |
- Calon, Tim G A, et al.
(författare)
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Minimally Invasive Ponto Surgery compared to the linear incision technique without soft tissue reduction for bone conduction hearing implants: study protocol for a randomized controlled trial.
- 2016
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Ingår i: Trials. - : Springer Science and Business Media LLC. - 1745-6215. ; 17:1
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Tidskriftsartikel (refereegranskat)abstract
- Over the last years, less invasive surgical techniques with soft tissue preservation for bone conduction hearing implants (BCHI) have been introduced such as the linear incision technique combined with a punch. Results using this technique seem favorable in terms of rate of peri-abutment dermatitis (PAD), esthetics, and preservation of skin sensibility. Recently, a new standardized surgical technique for BCHI placement, the Minimally Invasive Ponto Surgery (MIPS) technique has been developed by Oticon Medical AB (Askim, Sweden). This technique aims to standardize surgery by using a novel surgical instrumentation kit and minimize soft tissue trauma.A multicenter randomized controlled trial is designed to compare the MIPS technique to the linear incision technique with soft tissue preservation. The primary investigation center is Maastricht University Medical Center. Sixty-two participants will be included with a 2-year follow-up period. Parameters are introduced to quantify factors such as loss of skin sensibility, dehiscence of the skin next to the abutment, skin overgrowth, and cosmetic results. A new type of sampling method is incorporated to aid in the estimation of complications. To gain further understanding of PAD, swabs and skin biopsies are collected during follow-up visits for evaluation of the bacterial profile and inflammatory cytokine expression. The primary objective of the study is to compare the incidence of PAD during the first 3 months after BCHI placement. Secondary objectives include the assessment of parameters related to surgery, wound healing, pain, loss of sensibility of the skin around the implant, implant extrusion rate, implant stability measurements, dehiscence of the skin next to the abutment, and esthetic appeal. Tertiary objectives include assessment of other factors related to PAD and a health economic evaluation.This is the first trial to compare the recently developed MIPS technique to the linear incision technique with soft tissue preservation for BCHI surgery. Newly introduced parameters and sampling method will aid in the prediction of results and complications after BCHI placement.Registered at the CCMO register in the Netherlands on 24 November 2014: NL50072.068.14 . Retrospectively registered on 21 April 2015 at ClinicalTrials.gov: NCT02438618 . This trial is sponsored by Oticon Medical AB.
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| 49. |
- Colleoni, M, et al.
(författare)
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Timing of CMF chemotherapy in combination with tamoxifen in postmenopausal women with breast cancer: role of endocrine responsiveness of the tumor.
- 2005
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Ingår i: Annals of oncology : official journal of the European Society for Medical Oncology / ESMO. - : Elsevier BV. - 0923-7534. ; 16:5, s. 716-25
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Controversy persists about whether chemotherapy benefits all breast cancer patients. PATIENTS AND METHODS: In the International Breast Cancer Study Group (IBCSG) trial VII, 1212 postmenopausal patients with node-positive disease were randomized to receive tamoxifen for 5 years or tamoxifen plus three concurrent courses of cyclophosphamide, methotrexate and 5-fluorouracil ('classical' CMF) chemotherapy, either early, delayed or both. In IBCSG trial IX, 1669 postmenopausal patients with node-negative disease were randomized to receive either tamoxifen alone or three courses of adjuvant classical CMF prior to tamoxifen. Results were assessed according to estrogen receptor (ER) content of the primary tumor. RESULTS: For patients with node-positive, ER-positive disease, adding CMF either early, delayed or both reduced the risk of relapse by 21% (P=0.06), 26% (P=0.02) and 25% (P=0.02), respectively, compared with tamoxifen alone. There was no difference in disease-free survival when CMF was given prior to tamoxifen in patients with node-negative, ER-positive tumors. CONCLUSIONS: CMF given concurrently (early, delayed or both) with tamoxifen was more effective than tamoxifen alone for patients with node-positive, endocrine-responsive breast cancer, supporting late administration of chemotherapy even after commencement of tamoxifen. In contrast, sequential CMF and tamoxifen for patients with node-negative, endocrine-responsive disease was ineffective.
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| 50. |
- Cuzick, Jack, et al.
(författare)
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Prevention and early detection of prostate cancer.
- 2014
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Ingår i: The Lancet Oncology. - 1470-2045 .- 1474-5488. ; 15:11, s. e484-92
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Tidskriftsartikel (refereegranskat)abstract
- Prostate cancer is a common malignancy in men and the worldwide burden of this disease is rising. Lifestyle modifications such as smoking cessation, exercise, and weight control offer opportunities to reduce the risk of developing prostate cancer. Early detection of prostate cancer by prostate-specific antigen (PSA) screening is controversial, but changes in the PSA threshold, frequency of screening, and the use of other biomarkers have the potential to minimise the overdiagnosis associated with PSA screening. Several new biomarkers for individuals with raised PSA concentrations or those diagnosed with prostate cancer are likely to identify individuals who can be spared aggressive treatment. Several pharmacological agents such as 5α-reductase inhibitors and aspirin could prevent development of prostate cancer. In this Review, we discuss the present evidence and research questions regarding prevention, early detection of prostate cancer, and management of men either at high risk of prostate cancer or diagnosed with low-grade prostate cancer.
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