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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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  • Consoli, A, et al. (författare)
  • CT perfusion and angiographic assessment of pial collateral reperfusion in acute ischemic stroke: the CAPRI study
  • 2016
  • Ingår i: Journal of neurointerventional surgery. - : BMJ. - 1759-8486 .- 1759-8478. ; 8:12, s. 1211-
  • Tidskriftsartikel (refereegranskat)abstract
    • The purpose of this study was to evaluate the correlation between a novel angiographic score for collaterals and CT perfusion (CTP) parameters in patients undergoing endovascular treatment for acute ischemic stroke (AIS).Methods103 patients (mean age 66.7±12.7; 48.5% men) with AIS in the anterior circulation territory, imaged with non-contrast CT, CT angiography, and CTP, admitted within 8 h from symptom onset and treated with any endovascular approach, were retrospectively included in the study. Clinical, neuroradiological data, and all time intervals were collected. Careggi Collateral Score (CCS) was used for angiographic assessment of collaterals and the Alberta Stroke Program Early CT Score (ASPECTS) for semiquantitative analysis of CTP maps. Two centralized core laboratories separately reviewed angiographic data, whereas CT findings were evaluated by an expert neuroradiologist. Univariate and multivariate analysis were performed considering CCS both as an ordinal and a dichotomous variable.Results37/103 patients (35.9%) received intravenous tissue plasminogen activator. Median (IQR) ASPECTS was 9 (6–10) for admission CT, 9 (5–10) for cerebral blood volume (CBV) maps, 3 (2–3) for mean transit time maps, 3 (2–4), for cerebral blood flow maps, and 5 (3–7) for CTP mismatch. Univariate analysis showed a significant correlation between CCS and ASPECTS for all CTP parameters. Multivariate analysis confirmed an independent association only between CCS and CBV (p=0.020 when CCS was considered as a dichotomous variable, p=0.026 with ordinal CCS).ConclusionsA correlation between angiographic assessment of the collateral circulation and CTP seems to be present, suggesting that CCS may provide an indirect evaluation of the infarct core volume to consider for patient selection in AIS.
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  • Holmberg, Carl Jacob, et al. (författare)
  • The efficacy of immune checkpoint blockade for melanoma in-transit with or without nodal metastases - A multicenter cohort study
  • 2022
  • Ingår i: EUROPEAN JOURNAL OF CANCER. - : Elsevier BV. - 0959-8049 .- 1879-0852. ; 40:16
  • Tidskriftsartikel (refereegranskat)abstract
    • Purpose: Guidelines addressing melanoma in-transit metastasis (ITM) recommend immune checkpoint inhibitors (ICI) as a first-line treatment option, despite the fact that there are no efficacy data available from prospective trials for exclusively ITM disease. The study aims to analyze the outcome of patients with ITM treated with ICI based on data from a large cohort of patients treated at international referral clinics. Methods: A multicenter retrospective cohort study of patients treated between January 2015 and December 2020 from Australia, Europe, and the USA, evaluating treatment with ICI for ITM with or without nodal involvement (AJCC8 N1c, N2c, and N3c) and without distant disease (M0). Treatment was with PD-1 inhibitor (nivolumab or pembrolizumab) and/or CTLA-4 inhibitor (ipilimumab). The response was evaluated according to the RECIST criteria modified for cutaneous lesions. Results: A total of 287 patients from 21 institutions in eight countries were included. Immunotherapy was first-line treatment in 64 (22%) patients. PD-1 or CTLA-4 inhibitor monotherapy was given in 233 (81%) and 23 (8%) patients, respectively, while 31 (11%) received both in combination. The overall response rate was 56%, complete response (CR) rate was 36%, and progressive disease (PD) rate was 32%. Median PFS was ten months (95% CI 7.4-12.6 months) with a one-, two-, and five-year PFS rate of 48%, 33%, and 18%, respectively. Median MSS was not reached, and the one-, two-, and five-year MSS rates were 95%, 83%, and 71%, respectively. Conclusion: Systemic immunotherapy is an effective treatment for melanoma ITM. Future studies should evaluate the role of systemic immunotherapy in the context of multimodality therapy, including locoregional treatments such as surgery, intralesional therapy, and regional therapies.
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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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  • 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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  • 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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  • Gerdtsson, Axel, et al. (författare)
  • Validation of a prediction model for post-chemotherapy fibrosis in nonseminoma patients
  • 2023
  • Ingår i: Bju International. - 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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  • Grant, S. C., et al. (författare)
  • Alginate assessment by NMR microscopy
  • 2005
  • Ingår i: Journal of materials science. Materials in medicine. - : Springer Science and Business Media LLC. - 0957-4530 .- 1573-4838. ; 16:6, s. 511-514
  • Tidskriftsartikel (refereegranskat)abstract
    • Alginate hydrogels have long been used to encapsulate cells for the purpose of cell transplantation. However, they also have been criticized because they fail to consistently maintain their integrity for extended periods of time. Two issues of critical importance that have yet to be thoroughly addressed concerning the long-term integrity of alginate/poly-L-lysine/alginate microcapsules are: (i) are there temporal changes in the alginate/poly-L-lysine interaction and (ii) are there temporal changes in the alginate gel structure. NMR microscopy is a non-invasive analytical technique that can address these issues. in this report, we present data to demonstrate the utility of H-1 NMR microscopy to (i) visualize the poly-L-lysine layer in an effort to address the first question, and (ii) to observe temporal changes in the alginate matrix that may represent changes in the gel structure.
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  • Hallqvist, Andreas, 1973, et al. (författare)
  • Dose escalation to 84 Gy with concurrent chemotherapy in stage III NSCLC appears excessively toxic: Results from a prematurely terminated randomized phase II trial
  • 2018
  • Ingår i: Lung Cancer. - : Elsevier BV. - 0169-5002 .- 1872-8332. ; 122, s. 180-186
  • Tidskriftsartikel (refereegranskat)abstract
    • Objectives: Concurrent chemoradiotherapy is the mainstay treatment for NSCLC stage III disease. To investigate whether radiation dose escalation based on individual normal tissue constraints can improve outcome, the Swedish lung cancer study group launched this randomized phase II trial. Materials and Methods: NSCLC patients with stage III disease, good performance status (0-1) and adequate lung function (FEV1 > 1.0 L and CO diffusion capacity > 40%) received three cycles of cisplatin (75 mg/m(2) day 1) and vinorelbine (25 mg/m(2) day 1 and 8) every third week. Radiotherapy started concurrently with the second cycle, with either 2 Gy daily, 5 days a week, to 68 Gy (A) or escalated therapy (B) based on constraints to the spinal cord, esophagus and lungs up to 84 Gy by adding an extra fraction of 2 Gy per week. Results: A pre-planned safety analysis revealed excessive toxicity and decreased survival in the escalated arm, and the study was stopped. Thirty-six patients were included during 2011-2013 (56% male, 78% with adenocarcinoma, 64% with PS 0 and 53% with stage IIIB). The median progression-free survival (PFS) and overall survival (OS) were 11 and 17 months in arm B compared to the encouraging results of 28 and 45 months in the standard arm. The 1- and 3-year survival rates were 56% and 33% (B) and 72% and 56% (A), respectively. There were seven toxicity-related deaths due to esophageal perforations and pneumonitis: five in the escalated group and two with standard treatment. Conclusion: Dose-escalated concurrent chemoradiotherapy to 84 Gy to primary tumor and nodal disease is hazardous, with a high risk of excessive toxicity, whereas modern standard dose chemoradiotherapy with proper staging given in the control arm shows a promising outcome with a median survival of 45 months and a 3-year survival of 56% (NCT01664663).
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  • 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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  • 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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  • Nyman, J., et al. (författare)
  • Dose Escalated Chemo-RT to 84 Gy in Stage III NSCLC Appears Excessively Toxic : Results from a Randomized Phase II Trial
  • 2018
  • Ingår i: Journal of Thoracic Oncology. - : Elsevier. - 1556-0864 .- 1556-1380. ; 13:10, s. S373-S373
  • Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
    • Background: Concurrent chemoradiotherapy is the mainstay treatment for NSCLC stage III disease, however, with a rather high probability of locoregional and metastatic recurrence further treatment optimization is warranted. Based on previous one-armed trials with dose escalated radiotherapy, showing feasibility, the Swedish Lung Cancer Study Group aimed to investigate whether dose escalation based on individual normal tissue constraints could improve outcome in this randomized phase II trial.Method: NSCLC patients with stage III disease, good performance status (0-1), adequate lung function (FEV1 > 1.0 L and CO diff. > 40%) received three cycles of cisplatin (75 mg/m2 day 1) and vinorelbine (25 mg/m2 day 1 and 8) every third week. The radiotherapy started concurrently with the second cycle, with either 2 Gy daily, 5 days a week, to a total dose of 68 Gy (standard arm A) or escalated therapy (B) based on constraints to the spinal cord, esophagus and lungs up to 84 Gy by adding an extra fraction of 2 Gy per week while keeping the total treatment time constant at seven weeks with the same dose to involved nodes and primary tumor.Result: A pre-planned safety analysis revealed excessive toxicity and decreased survival in the escalated arm, and the study was stopped. Thirty-six patients were included during 2011-2013 (56% male, 78% with adenocarcinoma, 64% with PS 0 and 53% with stage IIIB). The median progression-free survival (PFS) and overall survival (OS) were 11 and 17 months in the dose escalated group compared to 28 and 45 months in the standard group. The 1-, 3- and 5-year survival rates were 56%, 33% and 17% in the escalated arm and 72%, 61% and 34% in the standard arm. There were four toxicity-related deaths due to esophageal perforations (one in arm A and three in arm B) and three deaths due to pneumonitis (one in arm A and two in arm B).Conclusion: Dose-escalated concurrent chemoradiotherapy to 84 Gy to primary tumor and nodal disease is hazardous, with a high risk of excessive toxicity, whereas modern standard dose chemoradiotherapy with proper staging given in the control arm shows a promising outcome with a median survival of 45 months and a 5-year survival of 34%. A possible step forward will be to improve systemic therapy, but future approaches with escalated radiotherapy may include boost techniques to remaining PET positive areas or different escalation schedules to the primary tumor and mediastinal nodes.
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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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41.
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42.
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43.
  • Sakai, S., et al. (författare)
  • Dust-plasma interaction through magnetosphere-ionosphere coupling in Saturn’s plasma disk
  • 2012
  • Ingår i: European Planetary Science Congress 2012, held 23-28 September, 2012 in Madrid, Spain. http://meetings.copernicus.org/epsc2012, id. EPSC2012-433.
  • Konferensbidrag (refereegranskat)abstract
    • The ion bulk speeds in the equatorial region of Saturn’s inner magnetosphere, according to data from the Langmuir Probe (LP) on board the Cassini spacecraft, are about 60% of the ideal co-rotation speed. These findings suggest that sub-micrometer negatively charged E ring dust contributes to the plasma dynamics in the plasma disk. We calculated the ion speeds by using multicomponent MHD equations, taking into account dust interactions to investigate the effects of ion-dust coulomb collision, mass loading, as well as taking into account magnetosphere-ionosphere coupling to investigate the effect of the magnetospheric electric field. The results show that the ion speeds can be significantly reduced by the electric fields generated by the ion-dust collisions when the dust density is high and the thickness of dust distribution is large. We also show that the ion speeds from our model are consistent with the LP observations when the maximum density of dust is larger than ~10\^5 m\^-3.
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44.
  • Sakai, S., et al. (författare)
  • Dust-plasma interaction through magnetosphere-ionosphere coupling in Saturn's plasma disk
  • 2013
  • Ingår i: Planetary and Space Science. - : Elsevier BV. - 0032-0633 .- 1873-5088. ; 75:1, s. 11-16
  • Forskningsöversikt (refereegranskat)abstract
    • The ion bulk speeds in the equatorial region of Saturn's inner magnetosphere, according to data from the Langmuir Probe (LP) on board the Cassini spacecraft, are about 60% of the ideal co-rotation speed; the ion speeds are between the co-rotation and Keplerian speeds (Holmberg et al.; Ion densities and velocities in the inner plasma torus of Saturn, Planetary and Space Science). These findings suggest that sub-micrometer negatively charged E ring dust contributes to the plasma dynamics in the plasma disk. We calculated the ion speeds by using a multi-species fluid model, taking into account dust interactions to investigate the effects of ion-dust coulomb collision, mass loading, as well as taking into account magnetosphere-ionosphere coupling to investigate the effect of the magnetospheric electric field. The results show that the ion speeds can be significantly reduced by the electric fields generated by the collisions between ions and dusts when the dust density is high and the thickness of dust distribution is large. We also show that the ion speeds from our model are consistent with the LP observations when the maximum density of dust is larger than ∼105 m-3.
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45.
  • Sedimbi, S. K., et al. (författare)
  • SUMO4 M55V polymorphism affects susceptibility to type I diabetes in HLA DR3- and DR4-positive Swedish patients
  • 2007
  • Ingår i: Genes Immun. - : Springer Science and Business Media LLC. - 1466-4879 .- 1476-5470. ; 8:6, s. 518-21
  • Tidskriftsartikel (refereegranskat)abstract
    • SUMO4 M55V, located in IDDM5, has been a focus for debate because of its association to type I diabetes (TIDM) in Asians but not in Caucasians. The current study aims to test the significance of M55V association to TIDM in a large cohort of Swedish Caucasians, and to test whether M55V is associated in those carrying human leukocyte antigen (HLA) class II molecules. A total of 673 TIDM patients and 535 age- and sex-matched healthy controls were included in the study. PCR-RFLP was performed to identify the genotype and allele variations. Our data suggest that SUMO4 M55V is not associated with susceptibility to TIDM by itself. When we stratified our patients and controls based on heterozygosity for HLA-DR3/DR4 and SUMO4 genotypes, we found that presence of SUMO4 GG increased further the relative risk conferred by HLA-DR3/DR4 to TIDM, whereas SUMO4 AA decreased the risk. From the current study, we conclude that SUMO4 M55V is associated with TIDM in association with high-risk HLA-DR3 and DR4, but not by itself.
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46.
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47.
  • Shin, J. H., et al. (författare)
  • IA-2 autoantibodies in incident type I diabetes patients are associated with a polyadenylation signal polymorphism in GIMAP5
  • 2007
  • Ingår i: Genes Immun. - : Springer Science and Business Media LLC. - 1466-4879 .- 1476-5470. ; 8:6, s. 503-12
  • 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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