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  • Fullman, N., et al. (författare)
  • 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
  • Ingår i: Lancet. - 0140-6736 .- 1474-547X. ; 390:10100, s. 1423-1459
  • 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)
  • Effects of chemotherapy and hormonal therapy for early breast cancer on recurrence and 15-year survival: an overview of the randomised trials
  • 2005
  • Ingår i: The Lancet. - 1474-547X. ; 365:9472, s. 1687-1717
  • 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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  • Pardo, M., et al. (författare)
  • Data preprocessing enhances the classification of different brands of Espresso coffee with an electronic nose
  • 2000
  • Ingår i: Sensors and actuators. B, Chemical. - 0925-4005 .- 1873-3077. ; 69:3, s. 397-403
  • Tidskriftsartikel (refereegranskat)abstract
    • Two different ways of preprocessing chemical sensor data are presented as a means to improve the interpretation and the classification ability of an electronic nose (EN). The practical problem at hand is the distinction between four commercial coffee blends - containing up to 12 types of coffees - all of which are to be consumed as Espresso. Coffee was sampled in three successive preparation phases: a beans, ground (powder) or liquid (the actual Espresso). In the case of beans, stress is put on the improved clusters visualization after the preprocessing and before the actual classification is performed. Different catalysed sensors and successive extractions were used to differentiate the response pattern towards the various coffees. The features which permitted the best samples' classification as judged from Principal Component Analysis (PCA) score plots were selected. To this end, an empirical search strategy inside the feature space is presented. Scores from PCA were subsequently utilized as inputs for a feed forward multilayer perceptron (MLP) with cross-validation resulting in 100% correct classification with just two sensors. In the case of ground coffee, a (supervised) drift compensation algorithm was developed. It essentially consists of removing the first principal component (PC) for every cluster since this is seen to be given by the drift. An 87.5% classification performance was achieved. Liquid coffee, on the other hand, was not successfully classified, probably due to the difficulty in assuring reproducible sampling conditions.
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  • Coombes, R C, et al. (författare)
  • Survival and safety of exemestane versus tamoxifen after 2-3 years' tamoxifen treatment (Intergroup Exemestane Study): a randomised controlled trial.
  • 2007
  • Ingår i: Lancet. - 1474-547X. ; 369:9561, s. 559-70
  • 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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  • Hedlund, J., et al. (författare)
  • Management of patients with community-acquired pneumonia treated in hospital in Sweden
  • 2002
  • Ingår i: Scandinavian Journal of Infectious Diseases. - 0036-5548. ; 34:12, s. 887-92
  • Tidskriftsartikel (refereegranskat)abstract
    • To investigate the management of patients with community-acquired pneumonia (CAP) treated in hospital in Sweden, a multicentre retrospective cohort study was performed with medical record review of 982 patients (mean age 63 y) at 17 departments of infectious diseases at hospitals in Sweden. Information on antimicrobial therapy, demographic characteristics, comorbid conditions, physical examination findings, and laboratory and microbiological test results were recorded. Outcome measures were in-hospital mortality and length of hospital stay (LOS). Cultures were obtained from blood in 80% and from sputum in 22% of the patients. A microbiological aetiology was determined for 23% of the patients, with Streptococcus pneumoniae as the dominating agent (9%). The initial antibiotic treatment was mostly given intravenously (78%). Penicillin (50%) or a cephalosporin (30%) was the most common choice. Both of these drugs were usually given as a single agent. The overall mortality was 3.5% and the mean LOS was 6.4 d. Thus, the outcome was favourable despite the empirical antibiotic treatment having a narrow spectrum compared with the broader approach recommended in most recent guidelines on the management of CAP. These findings suggest that a majority of patients who are hospitalized with moderately severe pneumonia can be treated initially with penicillin alone.
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  • Hultborn, Ragnar, 1946, et al. (författare)
  • Efficacy of pamidronate in breast cancer with bone metastases: a randomized, double-blind placebo-controlled multicenter study
  • 1999
  • Ingår i: Anticancer Res. - 0250-7005. ; 19:4C, s. 3383-92
  • Tidskriftsartikel (refereegranskat)abstract
    • PURPOSE: To evaluate the efficacy of pamidronate 60 mg i.v. q 4 weeks in women with advanced breast cancer with skeletal metastases. PATIENTS AND METHODS: 404 woman with skeletal metastases from breast cancer in Sweden and Norway were included in a randomized, placebo-controlled, multicenter study. Except for the study medication, other palliative treatment was chosen at the discretion of the physician. Skeletal related events, i.e. increased pain, treatment of hypercalcemia, pathologic fractures of long bones or pelvis, paralyses due to vertebral compression, palliative radiotherapy for skeletal metastases, surgery on bone and change of antitumor therapy were recorded every third month as well as a self-estimated pain-score using visual Analog Scales and analgesic consumption. RESULTS: There was a significantly increased time to progression of pain (p < 0.01), to hypercalcemic events (p < 0.05) as well as for the cumulative number of skeletal related events (p < 0.01) in favor for the pamidronate group. No statistically significant reduction of pathologic fractures of long bones or pelvis, or pareses due to vertebral compression occurred. No statistically significant differences were found for the need of radiotherapy and surgery on bone. The pamidronate group faired better regarding performance status (p < 0.05). There was a statistically not significant lower consumption of opioid analgesics in the pamidronate group (p = 0.14). CONCLUSION: Pamidronate 60 mg i.v. q 4 weeks reduces skeletal events and improves the quality of life in women with bone metastases from breast cancer.
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  • Landin-Olsson, Mona, et al. (författare)
  • Immunoreactive trypsin(Ogen) in the sera of children with recent-onset insulin-dependent diabetes and matched controls
  • 1990
  • Ingår i: Pancreas. - : Ovid Technologies (Wolters Kluwer Health). - 0885-3177. ; 5:3, s. 241-247
  • Tidskriftsartikel (refereegranskat)abstract
    • To evaluate the exocrine pancreatic function at the time of diagnosis of insulin-dependent diabetes mellitus, we determined immunoreactive an-odal and cathodal trypsin(ogen) levels in sera from almost all children (n = 375) 0-14 years of age in Sweden in whom diabetes developed during 1 year, and in sex-, age-, and geographically matched control subjects (n = 312). The median level of anodal trypsin(ogen) was 5 (quartile range, 3-7) µg/L in children with newly diagnosed diabetes, compared with a median level of 7 (quartile range, 4-8) µg/L in control subjects (p < 0.0001). Similarly, the median level of cathodal trypsin(ogen) was 8 (quartile range, 4-10) µg/L in children with diabetes, compared with a median level of 11 (quartile range, 7-15) µg/L in control subjects (p < 0.0001). The median of the individual ratios between cathodal and anodal trypsin(ogen) was 1.4 in the diabetic patients and 1.7 in the control children (p < 0.001). In a multivariate test, however, only the decrease in cathodal trypsin(ogen) concentration was associated with diabetes. The levels of trypsin(ogen)s did not correlate with levels of islet cell antibodies, present in 81% of the diabetic children. Several mechanisms may explain our findings, for example, similar pathogenetic factors may affect both the endocrine and exocrine pancreas simultaneously, a failing local trophic stimulation by insulin on the exocrine cells may decrease the trypsinogen production, and there may be an increased elimination of trypsin(ogen) because of higher filtration through the kidneys in the hyperglycemic state.
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  • Lindblad, K, et al. (författare)
  • An expanded CAG repeat sequence in spinocerebellar ataxia type 7
  • 1996
  • Ingår i: Genome research. - : Cold Spring Harbor Laboratory. - 1088-9051. ; 6:10, s. 965-971
  • Tidskriftsartikel (refereegranskat)abstract
    • Expanded CAG repeat sequences have been identified in the coding region of genes mutated in several neurodegenerative disorders, including spinocerebellar ataxia type 1 and Machado-Joseph disease. In all disorders described to date the CAG expansion codes for an elongated polyglutamine chain. An increased polyglutamine chain size leads to a more severe disease, thus correlating with the genetic anticipation seen in repeat expansion disorders. Spinocerebellar ataxia type 7 (SCA7) is an autosomal dominant spinocerebellar ataxia with anticipation and a progressive degeneration of the cerebellar cortex. Using repeat expansion detection (RED), a method in which a thermostable ligase is used to detect repeat expansions directly from genomic DNA, we have analyzed 8 SCA7 families for the presence of CAG repeat expansions. RED products of 150-240 bp were found in all affected individuals and found to cosegregate with the disease (P < 0.000001, n = 66), indicating strongly that a CAG expansion is the cause of SCA7. On the basis of a previously established correlation between RED product sizes and actual repeat sizes in Machado-Joseph disease, we were able to estimate the average expansion size in SCA7 to be 64 CAG copies.
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  • Roussos, E., et al. (författare)
  • Energetic electron observations of Rhea's magnetospheric interaction
  • 2012
  • Ingår i: Icarus. - : Elsevier BV. - 0019-1035 .- 1090-2643. ; 221:1, s. 116-134
  • Tidskriftsartikel (refereegranskat)abstract
    • Saturn's moon Rhea is thought to be a simple plasma absorber, however, energetic particle observations in its vicinity show a variety of unexpected and complex interaction features that do not conform with our current understanding about plasma absorbing interactions. Energetic electron data are especially interesting, as they contain a series of broad and narrow flux depletions on either side of the moon's wake. The association of these dropouts with absorption by dust and boulders orbiting within Rhea's Hill sphere was suggested but subsequently not confirmed, so in this study we review data from all four Cassini flybys of Rhea to date seeking evidence for alternative processes operating within the moon's interaction region. We focus on energetic electron observations, which we put in context with magnetometer, cold plasma density and energetic ion data. All flybys have unique features, but here we only focus on several structures that are consistently observed. The most interesting common feature is that of narrow dropouts in energetic electron fluxes, visible near the wake flanks. These are typically seen together with narrow flux enhancements inside the wake. A phase-space-density analysis for these structures from the first Rhea flyby (R1) shows that Liouville's theorem holds, suggesting that they may be forming due to rapid transport of energetic electrons from the magnetosphere to the wake, through narrow channels. A series of possibilities are considered to explain this transport process. We examined whether complex energetic electron drifts in the interaction region of a plasma absorbing moon (modeled through a hybrid simulation code) may allow such a transport. With the exception of several features (e.g. broadening of the central wake with increasing electron energy), most of the commonly observed interaction signatures in energetic electrons (including the narrow structures) were not reproduced. Additional dynamical processes, not simulated by the hybrid code, should be considered in order to explain the data. For the small scale features, the possibility that a flute (interchange) instability acts on the electrons is discussed. This instability is probably driven by strong gradients in the plasma pressure and the magnetic field magnitude: magnetometer observations show clearly signatures consistent with the (expected) plasma pressure loss due to ion absorption at Rhea. Another potential driver of the instability could have been gradients in the cold plasma density, which are, however, surprisingly absent from most crossings of Rhea's plasma wake. The lack of a density depletion in Rhea's wake suggests the presence of a local cold plasma source region. Hybrid plasma simulations show that this source cannot be the ionized component of Rhea's weak exosphere. It is probably related to accelerated photoelectrons from the moon's negatively charged surface, indicating that surface charging may play a very important role in shaping Rhea's magnetospheric interaction region. (C) 2012 Elsevier Inc. All rights reserved.
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  • Sanjeevi, Carani B., et al. (författare)
  • The risk conferred by HLA-DR and DQ for type 1 diabetes in 0-35-year age group are different in different regions of Sweden
  • 2008
  • Ingår i: Annals of the New York Academy of Sciences. - : Wiley. - 0077-8923 .- 1749-6632. - 9781573317337 ; 1150, s. 106-11
  • Tidskriftsartikel (refereegranskat)abstract
    • HLA DR4-DQ8 and DR3-DQ2 haplotypes account for 89% of newly diagnosed cases of type 1 diabetes (T1D) in Sweden. The presence of a single copy of DQ6 confers protection. The aim of the present study is to evaluate whether the risk conferred by high risk HLA DR and DQ to T1D is similar in all regions of Sweden and see whether there are any significant regional differences. The subjects comprised 799 consecutively diagnosed T1D patients and 585 age-, sex-, and geography-matched healthy controls in the age group 0-35 years. HLA typing for high-risk haplotypes was previously performed using PCR-SSOP and RFLP. The results showed that HLA DR3-DR4 gave an odds ratio of 8.14 for the whole of Sweden. However, when the study group was divided into six geographical regions, subjects from Stockholm had the highest OR, followed by those from Lund, Linköping, Gothenburg, Umeå, and Uppsala. Absolute protection was conferred by the presence of DQ6 in subjects from the Linköping region, but varied in the other regions. The frequency of DR3 and DQ2, DR4 and DQ8, DR15, and DQ6 in patients showed high linkage for each region, but were different between regions. In conclusion: The risk conferred by high-risk HLA varies in different regions for a homogenous population in Sweden. The results highlight the important role played by the various environmental factors in the precipitation of T1D.
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  • Bill-Axelson, Anna, et al. (författare)
  • Radical prostatectomy versus watchful waiting in localized prostate cancer : the Scandinavian prostate cancer group-4 randomized trial
  • 2008
  • Ingår i: Journal of the National Cancer Institute. - : Oxford University Press. - 0027-8874 .- 1460-2105. ; 100:16, s. 1144-1154
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: The benefit of radical prostatectomy in patients with early prostate cancer has been assessed in only one randomized trial. In 2005, we reported that radical prostatectomy improved prostate cancer survival compared with watchful waiting after a median of 8.2 years of follow-up. We now report results after 3 more years of follow-up.METHODS: From October 1, 1989, through February 28, 1999, 695 men with clinically localized prostate cancer were randomly assigned to radical prostatectomy (n = 347) or watchful waiting (n = 348). Follow-up was complete through December 31, 2006, with histopathologic review and blinded evaluation of causes of death. Relative risks (RRs) were estimated using the Cox proportional hazards model. Statistical tests were two-sided.RESULTS: During a median of 10.8 years of follow-up (range = 3 weeks to 17.2 years), 137 men in the surgery group and 156 in the watchful waiting group died (P = .09). For 47 of the 347 men (13.5%) who were randomly assigned to surgery and 68 of the 348 men (19.5%) who were not, death was due to prostate cancer. The difference in cumulative incidence of death due to prostate cancer remained stable after about 10 years of follow-up. At 12 years, 12.5% of the surgery group and 17.9% of the watchful waiting group had died of prostate cancer (difference = 5.4%, 95% confidence interval [CI] = 0.2 to 11.1%), for a relative risk of 0.65 (95% CI = 0.45 to 0.94; P = .03). The difference in cumulative incidence of distant metastases did not increase beyond 10 years of follow-up. At 12 years, 19.3% of men in the surgery group and 26% of men in the watchful waiting group had been diagnosed with distant metastases (difference = 6.7%, 95% CI = 0.2 to 13.2%), for a relative risk of 0.65 (95% CI = 0.47 to 0.88; P = .006). Among men who underwent radical prostatectomy, those with extracapsular tumor growth had 14 times the risk of prostate cancer death as those without it (RR = 14.2, 95% CI = 3.3 to 61.8; P < .001).CONCLUSION: Radical prostatectomy reduces prostate cancer mortality and risk of metastases with little or no further increase in benefit 10 or more years after surgery. 
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  • Botling, Johan, et al. (författare)
  • Biomarker Discovery in Non-Small Cell Lung Cancer : Integrating Gene Expression Profiling, Meta-analysis, and Tissue Microarray Validation
  • 2013
  • Ingår i: Clinical Cancer Research. - 1078-0432 .- 1557-3265. ; 19:1, s. 194-204
  • Tidskriftsartikel (refereegranskat)abstract
    • Purpose: Global gene expression profiling has been widely used in lung cancer research to identify clinically relevant molecular subtypes as well as to predict prognosis and therapy response. So far, the value of these multigene signatures in clinical practice is unclear, and the biologic importance of individual genes is difficult to assess, as the published signatures virtually do not overlap.Experimental Design: Here, we describe a novel single institute cohort, including 196 non-small lung cancers (NSCLC) with clinical information and long-term follow-up. Gene expression array data were used as a training set to screen for single genes with prognostic impact. The top 450 probe sets identified using a univariate Cox regression model (significance level P < 0.01) were tested in a meta-analysis including five publicly available independent lung cancer cohorts (n = 860).Results: The meta-analysis revealed 14 genes that were significantly associated with survival (P < 0.001) with a false discovery rate < 1%. The prognostic impact of one of these genes, the cell adhesion molecule 1 (CADM1), was confirmed by use of immunohistochemistry on tissue microarrays from 2 independent NSCLC cohorts, altogether including 617 NSCLC samples. Low CADM1 protein expression was significantly associated with shorter survival, with particular influence in the adenocarcinoma patient subgroup.Conclusions: Using a novel NSCLC cohort together with a meta-analysis validation approach, we have identified a set of single genes with independent prognostic impact. One of these genes, CADM1, was further established as an immunohistochemical marker with a potential application in clinical diagnostics. Clin Cancer Res; 19(1); 194-204. (c) 2012 AACR.
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  • Calon, Tim G A, et al. (författare)
  • 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
  • Ingår i: Trials. - : Springer Science and Business Media LLC. - 1745-6215. ; 17:1
  • 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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  • Calon, T. G. A., et al. (författare)
  • Minimally Invasive Ponto Surgery Versus the Linear Incision Technique With Soft Tissue Preservation for Bone Conduction Hearing Implants: A Multicenter Randomized Controlled Trial
  • 2018
  • Ingår i: Otology & Neurotology. - : Ovid Technologies (Wolters Kluwer Health). - 1531-7129 .- 1537-4505. ; 39:7, s. 882-893
  • 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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30.
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31.
  • Carlsson, Anna, et al. (författare)
  • Identification of a susceptibility locus for migraine with and without aura on 6p12.2-p21.1
  • 2002
  • Ingår i: Neurology. - : Lippincott Williams & Wilkins. - 0028-3878 .- 1526-632X. ; 59:11, s. 1804-1807
  • Tidskriftsartikel (refereegranskat)abstract
    • Migraine is the most common type of chronic episodic headache. To find novel susceptibility genes for familial migraine with and without aura, a genomewide screen was performed in a large family from northern Sweden. Evidence of linkage was obtained on chromosome 6p12.2-p21.1, with a maximum two-point lod score of 5.41 for marker D6S452. The patients with migraine shared a common haplotype of 10 Mb between markers D6S1650 and D6S1960.
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32.
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33.
  • Christlieb, N., et al. (författare)
  • 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
  • Ingår i: Astronomy & Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 428:3, s. 1027-1037
  • 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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34.
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35.
  • Gamier, P., et al. (författare)
  • Deriving the characteristics of warm electrons (100-500 eV) in the magnetosphere of Saturn with the Cassini Langmuir probe
  • 2014
  • Ingår i: Planetary and Space Science. - : Elsevier BV. - 0032-0633 .- 1873-5088. ; 104, s. 173-184
  • Tidskriftsartikel (refereegranskat)abstract
    • Though Langmuir probes (LP) are designed to investigate cold plasma regions (e.g. ionospheres), a recent analysis revealed a strong sensitivity of the Cassini LP measurements to hundreds of eV electrons. These warm electrons impact the surface of the probe and generate a significant current of secondary electrons, that impacts both the DC level and the slope of the current-voltage curve of the LP (for negative potentials) through energetic contributions that may be modeled with a reasonable precision. We show here how to derive information about the incident warm electrons from the analysis of these energetic contributions, in the regions where the cold plasma component is small with an average temperature in the range similar to [100-500] eV. First, modeling the energetic contributions (based on the incident electron flux given by a single anode of the CAPS spectrometer) allows us to provide information about the pitch angle anisotropies of the incident hundreds of eV electrons. The modeling reveals indeed sometimes a large variability of the estimated maximum secondary electron yield (which is a constant for a surface material) needed to reproduce the observations. Such dispersions give evidence for strong pitch angle anisotropies of the incident electrons, and using a functional form of the pitch angle distribution even allows us to derive the real peak angle of the distribution. Second, rough estimates of the total electron temperature may be derived in the regions where the warm electrons are dominant and thus strongly influence the LP observations, i.e. when the average electron temperature is in the range similar to [100-500] eV. These regions may be identified from the LP observations through large positive values of the current-voltage slope at negative potentials. The estimated temperature may then be used to derive the electron density in the same region, with estimated densities between similar to 0.1 and a few particles/cm(3) (cc). The derived densities are in better agreement with the CAPS measurements than the values derived from the proxy technique (Morooka et al., 2009) based on the floating potential of the LP. Both the electron temperature and the density estimates lie outside the classical capabilities of the LP, which are essentially n(e) > 5 cc and T-e <5 eV at Saturn. This approximate derivation technique may be used in the regions where the cold plasma component is small with an average temperature in the range similar to [100-500] eV, which occurs often in the L range 6.4-9.4 R-S when Cassini is off the equator, but may occur anywhere in the magnetosphere. This technique may be all the more interesting since the CAPS instrument was shut down, and, though it cannot replace the CAPS instrument, the technique can provide useful information about the electron moments, with probably even better estimates than CAPS in some cases (when the plasma is strongly anisotropic). Finally, a simple modeling approach allows us to predict the impact of the energetic contributions on LP measurements in any plasma environment whose characteristics (density, temperature, etc.) are known. LP observations may thus be influenced by warm electrons in several planetary plasma regions in the solar system, and ambient magnetospheric electron density and temperature could be estimated in some of them (e.g. around several galilean satellites) through the use of Langmuir probes.
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36.
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37.
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38.
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39.
  • Gerdtsson, Axel, et al. (författare)
  • Validation of a prediction model for post-chemotherapy fibrosis in nonseminoma patients
  • 2023
  • Ingår i: Bju International. - : John Wiley & Sons. - 1464-4096 .- 1464-410X. ; 132:3, s. 329-336
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective To validate Vergouwe's prediction model using the Swedish and Norwegian Testicular Cancer Group (SWENOTECA) RETROP database and to define its clinical utility. Materials and methods Vergouwe's prediction model for benign histopathology in post-chemotherapy retroperitoneal lymph node dissection (PCRPLND) uses the following variables: presence of teratoma in orchiectomy specimen; pre-chemotherapy level of alphafetoprotein; b-Human chorionic gonadotropin and lactate dehydrogenase; and lymph node size pre- and postchemotherapy. Our validation cohort consisted of patients included in RETROP, a prospective population-based database of patients in Sweden and Norway with metastatic nonseminoma, who underwent PC-RPLND in the period 2007-2014. Discrimination and calibration analyses were used to validate Vergouwe's prediction model results. Calibration plots were created and a Hosmer-Lemeshow test was calculated. Clinical utility, expressed as opt-out net benefit (NBopt-out), was analysed using decision curve analysis. Results Overall, 284 patients were included in the analysis, of whom 130 (46%) had benign histology after PC-RPLND. Discrimination analysis showed good reproducibility, with an area under the receiver-operating characteristic curve (AUC) of 0.82 (95% confidence interval 0.77-0.87) compared to Vergouwe's prediction model (AUC between 0.77 and 0.84). Calibration was acceptable with no recalibration. Using a prediction threshold of 70% for benign histopathology, NBopt-out was 0.098. Using the model and this threshold, 61 patients would have been spared surgery. However, only 51 of 61 were correctly classified as benign. Conclusions The model was externally validated with good reproducibility. In a clinical setting, the model may identify patients with a high chance of benign histopathology, thereby sparing patients of surgery. However, meticulous follow-up is required.
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40.
  • Gillman, Anna, et al. (författare)
  • Oseltamivir-Resistant Influenza A (H1N1) Virus Strain with an H274Y Mutation in Neuraminidase Persists without Drug Pressure in Infected Mallards
  • 2015
  • Ingår i: Applied and Environmental Microbiology. - : American Society for Microbiology. - 0099-2240 .- 1098-5336. ; 81:7, s. 2378-2383
  • Tidskriftsartikel (refereegranskat)abstract
    • Influenza A virus (IAV) has its natural reservoir in wild waterfowl and emerging human IAVs often contain gene segments from avian viruses. The active drug metabolite of oseltamivir (oseltamivir carboxylate (OC)), stockpiled as Tamiflu® for influenza pandemic preparedness, is not removed by conventional sewage treatment and has been detected in river water. There, it may there exert evolutionary pressure on avian IAV in waterfowl, resulting in development of resistant viral variants. A resistant avian IAV can circulate among wild birds only if resistance does not restrict viral fitness and if the resistant virus can persist without continuous drug pressure. In this in vivo Mallard (Anas platyrhynchos) study we tested if an OC-resistant avian IAV strain (A(H1N1)/NA-H274Y) could retain resistance while drug pressure was gradually removed. Successively infected Mallards were exposed to decreasing levels of OC, and fecal samples were analyzed for neuraminidase sequence and phenotypic resistance. No reversion to wild-type virus was observed during the experiment, which included 17 days of viral transmission in 10 ducks exposed to OC concentrations below resistance induction levels. We conclude that resistance in avian IAV, induced by OC exposure of the natural host, can persist in absence of the drug. Thus, there is a risk that human pathogenic IAVs that evolve from IAVs circulating among wild birds may contain resistance mutations. An oseltamivir resistant pandemic IAV would be a substantial public health threat. Therefore, our observations underscore the need for prudent oseltamivir use, upgraded sewage treatment and resistance surveillance of IAV in wild birds.
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41.
  • Grinin, V. P., et al. (författare)
  • Modelling UX Ori star eclipses based on spectral observations with the Nordic Optical Telescope - I. RR Tau
  • 2023
  • Ingår i: Monthly notices of the Royal Astronomical Society. - : Oxford University Press. - 0035-8711 .- 1365-2966. ; 524:3, s. 4047-4061
  • Tidskriftsartikel (refereegranskat)abstract
    • Based on observations obtained with the Nordic Optical Telescope (NOT) we investigate the spectral variability of the Herbig Ae star RR Tau. This star belongs to the UX Ori family, characterized by very deep fadings caused by the screening of the star with opaque fragments (clouds) of the protoplanetary discs. At the moments of such minima one observes strong spectral variability due to the fact that the dust cloud occults, for an observer, not only the star but also a part of the region where the emission spectrum originates. We calculated a series of obscuration models to interpret the observed variability of the H a line parameters. We consider two main obscuration scenarios: (1) the dust screen rises vertically above the circumstellar disc, and (2) the screen intersects the line-of-sight moving azimuthally with the disc. In both cases, the model of the emission region consists of a compact magnetosphere and a magnetocentrifugal disc wind. Comparison with observations shows that the first scenario explains well the variability of the radiation flux, the equivalent width, as well as the asymmetry of the H a line during eclipses, while the second scenario explains them only partly. This permits us to suggest that in the case of RR Tau, the main causes of the eclipses are either a structured disc wind, or the charged dust lifted along the field lines of the poloidal component of the magnetic field of the circumstellar disc.
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42.
  • Gruber, G, et al. (författare)
  • Extracapsular tumor spread and the risk of local, axillary and supraclavicular recurrence in node-positive, premenopausal patients with breast cancer.
  • 2008
  • Ingår i: Annals of oncology : official journal of the European Society for Medical Oncology / ESMO. - : Elsevier BV. - 1569-8041. ; 19:8, s. 1393-401
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Extracapsular tumor spread (ECS) has been identified as a possible risk factor for breast cancer recurrence, but controversy exists regarding its role in decision making for regional radiotherapy. This study evaluates ECS as a predictor of local, axillary, and supraclavicular recurrence. PATIENTS AND METHODS: International Breast Cancer Study Group Trial VI accrued 1475 eligible pre- and perimenopausal women with node-positive breast cancer who were randomly assigned to receive three to nine courses of classical combination chemotherapy with cyclophosphamide, methotrexate, and fluorouracil. ECS status was determined retrospectively in 933 patients based on review of pathology reports. Cumulative incidence and hazard ratios (HRs) were estimated using methods for competing risks analysis. Adjustment factors included treatment group and baseline patient and tumor characteristics. The median follow-up was 14 years. RESULTS: In univariable analysis, ECS was significantly associated with supraclavicular recurrence (HR = 1.96; 95% confidence interval 1.23-3.13; P = 0.005). HRs for local and axillary recurrence were 1.38 (P = 0.06) and 1.81 (P = 0.11), respectively. Following adjustment for number of lymph node metastases and other baseline prognostic factors, ECS was not significantly associated with any of the three recurrence types studied. CONCLUSIONS: Our results indicate that the decision for additional regional radiotherapy should not be based solely on the presence of ECS.
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43.
  • Herlitz, Johan, et al. (författare)
  • A comparison between patients suffering in-hospital and out-of-hospital cardiac arrest in terms of treatment and outcome
  • 2000
  • Ingår i: Journal of Internal Medicine. - : Wiley-Blackwell Publishing Ltd.. - 0954-6820 .- 1365-2796. ; 248:1, s. 53-60
  • Tidskriftsartikel (refereegranskat)abstract
    • AIM: To compare treatment and outcome amongst patients suffering in-hospital and out-of-hospital cardiac arrest in the same community. PATIENTS: All patients suffering in-hospital cardiac arrest in Sahlgrenska University Hospital covering half the catchment area of the community of Göteborg (500 000 inhabitants) and all patients suffering out-of-hospital cardiac arrest in the community of Göteborg. Criteria for inclusion were that resuscitation efforts should have been attempted. TIME OF SURVEY: From 1 November 1994 to 1 November 1997. METHODS: Data were recorded both prospectively and retrospectively. RESULTS: In total, 422 patients suffered in-hospital cardiac arrest and 778 patients suffered out-of-hospital cardiac arrest. Patients with in-hospital cardiac arrest included more women and were more frequently found in ventricular fibrillation. The median interval between collapse and defibrillation was 2 min in in-hospital cardiac arrest compared with 7 min in out-of-hospital cardiac arrest (< 0.001). The proportion of patients being discharged from hospital was 37.5% after in-hospital cardiac arrest, compared with 8.7% after out-of-hospital cardiac arrest (P < 0.001). Corresponding figures for patients found in ventricular fibrillation were 56.9 vs. 19.7% (P < 0.001) and for patients found in asystole 25.2 vs. 1.8% (P < 0.001). CONCLUSION: In a survey evaluating patients with in-hospital and out-of-hospital cardiac arrest in whom resuscitation efforts were attempted, we found that the former group had a survival rate more than four times higher than the latter. Possible strong contributing factors to this observation are: (i) shorter time interval to start of treatment, and (ii) a prepared selection for resuscitation efforts.
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44.
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45.
  • Holmberg, K, et al. (författare)
  • Generation and phenotypic characterization of a galanin overexpressing mouse
  • 2005
  • Ingår i: Neuroscience. - : Elsevier BV. - 0306-4522 .- 1873-7544. ; 133:1, s. 59-77
  • Tidskriftsartikel (refereegranskat)abstract
    • In most parts of the peripheral nervous system galanin is expressed at very low levels. To further understand the functional role of galanin, a mouse overexpressing galanin under the platelet-derived growth factor-B was generated, and high levels of galanin expression were observed in several peripheral tissues and spinal cord. Thus, a large proportion of neurons in autonomic and sensory ganglia were galanin-positive, as were most spinal motor neurons. Strong galanin-like immunoreactivity was also seen in nerve terminals in the corresponding target tissues, including skin, blood vessels, sweat and salivary glands, motor end-plates and the gray matter of the spinal cord. In transgenic superior cervical ganglia around half of all neuron profiles expressed galanin mRNA but axotomy did not cause a further increase, even if mRNA levels were increased in individual neurons. In transgenic dorsal root ganglia galanin mRNA was detected in around two thirds of all neuron profiles, including large ones, and after axotomy the percentage of galanin neuron profiles was similar in overexpressing and wild type mice. Axotomy reduced the total number of DRG neurons less in overexpressing than in wild type mice, indicating a modest rescue effect. Aging by itself increased galanin expression in the superior cervical ganglion in wild type and transgenic mice, and in the latter also in preganglionic cholinergic neurons projecting to the superior cervical ganglion. Galanin overexpressing mice showed an attenuated plasma extravasation, an increased pain response in the formalin test, and changes in muscle physiology, but did not differ from wild type mice in sudomotor function. These findings suggest that overexpressed galanin in some tissues of these mice can be released and via a receptor-mediated action influence pathophysiological processes. © 2005 Published by Elsevier Ltd on behalf of IBRO.
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46.
  • Holmberg, M. K. G., et al. (författare)
  • Cassini-Plasma Interaction Simulations Revealing the Cassini Ion Wake Characteristics : Implications for In-Situ Data Analyses and Ion Temperature Estimates
  • 2021
  • Ingår i: Journal of Geophysical Research - Space Physics. - : American Geophysical Union (AGU). - 2169-9380 .- 2169-9402. ; 126:8
  • Tidskriftsartikel (refereegranskat)abstract
    • We have used Spacecraft Plasma Interaction Software (SPIS) simulations to study the characteristics (i.e., dimensions, ion depletion, and evolution with the changing spacecraft attitude) of the Cassini ion wake. We focus on two regions, the plasma disk at 4.5-€“4.7 RS, where the most prominent wake structure will be formed, and at 7.6 RS, close to the maximum distance at which a wake structure can be detected in the Cassini Langmuir probe (LP) data. This study also reveals how the ion wake and the spacecraft plasma interaction have impacted the Cassini LP measurements in the studied environments, for example, with a strong decrease in the measured ion density but with minor interference from the photoelectrons and secondary electrons originating from the spacecraft. The simulated ion densities and spacecraft potentials are in very good agreement with the LP measurements. This shows that SPIS is an excellent tool to use for analyses of LP data, when spacecraft material properties and environmental parameters are known and used correctly. The simulation results are also used to put constraints on the ion temperature estimates in the inner magnetosphere of Saturn. The best agreement between the simulated and measured ion density is obtained using an ion temperature of 8 eV at ∼4.6 RS. This study also shows that SPIS simulations can be used in order to better constrain plasma parameters in regions where accurate measurements are not available.
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47.
  • Klyuchnikov, Evgeny, et al. (författare)
  • Reduced-Intensity Allografting as First Transplantation Approach in Relapsed/Refractory Grades One and Two Follicular Lymphoma Provides Improved Outcomes in Long-Term Survivors
  • 2015
  • Ingår i: Biology of blood and marrow transplantation. - : Elsevier BV. - 1083-8791 .- 1523-6536. ; 21:12, s. 2091-2099
  • Tidskriftsartikel (refereegranskat)abstract
    • This study was conducted to compare long-term outcomes in patients with refractory/relapsed grades 1 and 2 follicular lymphoma (FL) after allogeneic (allo) versus autologous (auto) hematopoietic cell transplantation (HCT) in the rituximab era. Adult patients with relapsed/refractory grades 1 and 2 FL undergoing first reduced-intensity allo-HCT or first autograft during 2000 to 2012 were evaluated. A total of 518 rituximab-treated patients were included. Allo-HCT patients were younger and more heavily pretreated, and more patients had advanced stage and chemoresistant disease. The 5-year adjusted probabilities, comparing auto-HCT versus allo-HCT groups for nonrelapse mortality (NRM) were 5% versus 26% (P <.0001); relapse/progression: 54% versus 20% (P <.0001); progression-free survival (PFS): 41% versus 58% (P <.001), and overall survival (OS): 74% versus 66% (P =.05). Auto-HCT was associated with a higher risk of relapse/progression beyond 5 months after HCT (relative risk [RR], 4.4; P <.0001) and worse PFS (RR, 2.9; P <.0001) beyond 11 months after HCT. In the first 24 months after HO', auto-HCT was associated with improved OS (RR,.41; P <.0001), but beyond 24 months, it was associated with inferior OS (RR, 2.2; P =.006). A landmark analysis of patients alive and progression-free at 2 years after HO' confirmed these observations, showing no difference in further NRM between both groups, but there was significantly higher risk of relapse/progression (RR, 7.3; P <.0001) and inferior PFS (RR, 3.2; P <.0001) and OS (RR, 2.1; P =.04) after auto-HCT. The 10-year cumulative incidences of second hematological malignancies after allo-HCT and auto-HCT were 0% and 7%, respectively. Auto-HCT and reduced-intensity conditioned allo-HCT as first transplantation approach can provide durable disease control in grades 1 and 2 FL patients. Continued disease relapse risk after auto-HCT translates into improved PFS and OS after allo-HCT in long-term survivors.
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48.
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49.
  • Malmström, Per, et al. (författare)
  • Breast conservation surgery, with and without radiotherapy, in women with lymph node-negative breast cancer: a randomised clinical trial in a population with access to public mammography screening.
  • 2003
  • Ingår i: European journal of cancer (Oxford, England : 1990). - 0959-8049. ; 39, s. 1690-
  • Tidskriftsartikel (refereegranskat)abstract
    • The effect of postoperative radiotherapy after sector resection for stage I-II lymph node-negative breast cancer was evaluated in a patient population with access to public mammographical screening. 1187 women were randomised to no further treatment or postoperative radiotherapy following a standardised sector resection and axillary dissection. Radiation was administered to a dose of 48-54 Gy. Median age was 60 years, and median size of the detected tumours was 12 mm. Of the women 65% had their tumours detected by mammographical screening. The relative risk (RR) of ipsilateral breast recurrence was significantly higher in the non-irradiated patients compared with the irradiated patients, RR=3.33 (95% Confidence Interval (CI) 2.13-5.19, P<0.001). The corresponding cumulative incidence at 5 years was 14% versus 4%, respectively. Overall survival (OS) was similar, RR=1.16 (95% CI 0.81-1.65, P=0.41), with 5 year probabilities of 93 and 94%, respectively. Recurrence-free survival (RFS) at 5 years was significantly lower in the non-irradiated women, 77% versus 88% (P<0.001). Although women above 49 years of age, whose tumours were detected with mammographical screening, had the lowest rate of ipsilateral breast recurrence in this study, the cumulative incidence of such event amounted to 10% at 5 years if radiotherapy was not given. Such a recurrence rate has been considered as unacceptably high, but is, however, in the same range as that reported after lumpectomy and postoperative radiotherapy in published series.
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