1. |
- Horwich, A, et al.
(författare)
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EAU–ESMO consensus statements on the management of advanced and variant bladder cancer - an international collaborative multi-stakeholder effort : under the auspices of the EAU and ESMO Guidelines Committees
- 2019
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Ingår i: Annals of Oncology. - : Oxford University Press. - 0923-7534 .- 1569-8041. ; 30:11, s. 1697-1727
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Although guidelines exist for advanced and variant bladder cancer management, evidence is limited/conflicting in some areas and the optimal approach remains controversial.OBJECTIVE: To bring together a large multidisciplinary group of experts to develop consensus statements on controversial topics in bladder cancer management.DESIGN: A steering committee compiled proposed statements regarding advanced and variant bladder cancer management which were assessed by 113 experts in a Delphi survey. Statements not reaching consensus were reviewed; those prioritised were revised by a panel of 45 experts before voting during a consensus conference.SETTING: Online Delphi survey and consensus conference.PARTICIPANTS: The European Association of Urology (EAU), the European Society for Medical Oncology (ESMO), experts in bladder cancer management.OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Statements were ranked by experts according to their level of agreement: 1-3 (disagree), 4-6 (equivocal), 7-9 (agree). A priori (level 1) consensus was defined as ≥70% agreement and ≤15% disagreement, or vice versa. In the Delphi survey, a second analysis was restricted to stakeholder group(s) considered to have adequate expertise relating to each statement (to achieve level 2 consensus).RESULTS AND LIMITATIONS: Overall, 116 statements were included in the Delphi survey. Of these, 33 (28%) statements achieved level 1 consensus and 49 (42%) statements achieved level 1 or 2 consensus. At the consensus conference, 22 of 27 (81%) statements achieved consensus. These consensus statements provide further guidance across a broad range of topics, including the management of variant histologies, the role/limitations of prognostic biomarkers in clinical decision making, bladder preservation strategies, modern radiotherapy techniques, the management of oligometastatic disease and the evolving role of checkpoint inhibitor therapy in metastatic disease.CONCLUSIONS: These consensus statements provide further guidance on controversial topics in advanced and variant bladder cancer management until a time where further evidence is available to guide our approach.
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3. |
- Aarestrup, FM, et al.
(författare)
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Towards a European health research and innovation cloud (HRIC)
- 2020
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Ingår i: Genome medicine. - : Springer Science and Business Media LLC. - 1756-994X. ; 12:1, s. 18-
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Tidskriftsartikel (refereegranskat)abstract
- The European Union (EU) initiative on the Digital Transformation of Health and Care (Digicare) aims to provide the conditions necessary for building a secure, flexible, and decentralized digital health infrastructure. Creating a European Health Research and Innovation Cloud (HRIC) within this environment should enable data sharing and analysis for health research across the EU, in compliance with data protection legislation while preserving the full trust of the participants. Such a HRIC should learn from and build on existing data infrastructures, integrate best practices, and focus on the concrete needs of the community in terms of technologies, governance, management, regulation, and ethics requirements. Here, we describe the vision and expected benefits of digital data sharing in health research activities and present a roadmap that fosters the opportunities while answering the challenges of implementing a HRIC. For this, we put forward five specific recommendations and action points to ensure that a European HRIC: i) is built on established standards and guidelines, providing cloud technologies through an open and decentralized infrastructure; ii) is developed and certified to the highest standards of interoperability and data security that can be trusted by all stakeholders; iii) is supported by a robust ethical and legal framework that is compliant with the EU General Data Protection Regulation (GDPR); iv) establishes a proper environment for the training of new generations of data and medical scientists; and v) stimulates research and innovation in transnational collaborations through public and private initiatives and partnerships funded by the EU through Horizon 2020 and Horizon Europe.
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4. |
- Brausi, M., et al.
(författare)
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ECCO Essential Requirements for Quality Cancer Care: Prostate cancer
- 2020
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Ingår i: Critical Reviews in Oncology Hematology. - : Elsevier BV. - 1040-8428. ; 148
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Tidskriftsartikel (refereegranskat)abstract
- Background: ECCO Essential Requirements for Quality Cancer Care (ERQCC) are written by experts representing all disciplines involved in cancer care in Europe. They give oncology teams, patients, policymakers and managers an overview of essential care throughout the patient journey. Prostate cancer: Prostate cancer is the second most common male cancer and has a wide variation in outcomes in Europe. It has complex diagnosis and treatment challenges, and is a major healthcare burden. Care must only be a carried out in prostate/urology cancer units or centres that have a core multidisciplinary team (MDT) and an extended team of health professionals. Such units are far from universal in European countries. To meet European aspirations for comprehensive cancer control, healthcare organisations must consider the requirements in this paper, paying particular attention to multidisciplinarity and patient-centred pathways from diagnosis, to treatment, to survivorship.
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5. |
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6. |
- Witjes, J. Alfred, et al.
(författare)
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EAU-ESMO Consensus Statements on the Management of Advanced and Variant Bladder Cancer – An International Collaborative Multistakeholder Effort : Under the Auspices of the EAU-ESMO Guidelines Committees
- 2020
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Ingår i: European Urology. - : Elsevier. - 0302-2838 .- 1873-7560. ; 77:2, s. 223-250
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Although guidelines exist for advanced and variant bladder cancer management, evidence is limited/conflicting in some areas and the optimal approach remains controversial.OBJECTIVE: To bring together a large multidisciplinary group of experts to develop consensus statements on controversial topics in bladder cancer management.DESIGN: A steering committee compiled proposed statements regarding advanced and variant bladder cancer management which were assessed by 113 experts in a Delphi survey. Statements not reaching consensus were reviewed; those prioritised were revised by a panel of 45 experts prior to voting during a consensus conference.SETTING: Online Delphi survey and consensus conference.PARTICIPANTS: The European Association of Urology (EAU), the European Society for Medical Oncology (ESMO), experts in bladder cancer management.OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Statements were ranked by experts according to their level of agreement: 1-3 (disagree), 4-6 (equivocal), and 7-9 (agree). A priori (level 1) consensus was defined as ≥70% agreement and ≤15% disagreement, or vice versa. In the Delphi survey, a second analysis was restricted to stakeholder group(s) considered to have adequate expertise relating to each statement (to achieve level 2 consensus).RESULTS AND LIMITATIONS: Overall, 116 statements were included in the Delphi survey. Of these statements, 33 (28%) achieved level 1 consensus and 49 (42%) achieved level 1 or 2 consensus. At the consensus conference, 22 of 27 (81%) statements achieved consensus. These consensus statements provide further guidance across a broad range of topics, including the management of variant histologies, the role/limitations of prognostic biomarkers in clinical decision making, bladder preservation strategies, modern radiotherapy techniques, the management of oligometastatic disease, and the evolving role of checkpoint inhibitor therapy in metastatic disease.CONCLUSIONS: These consensus statements provide further guidance on controversial topics in advanced and variant bladder cancer management until a time when further evidence is available to guide our approach.PATIENT SUMMARY: This report summarises findings from an international, multistakeholder project organised by the EAU and ESMO. In this project, a steering committee identified areas of bladder cancer management where there is currently no good-quality evidence to guide treatment decisions. From this, they developed a series of proposed statements, 71 of which achieved consensus by a large group of experts in the field of bladder cancer. It is anticipated that these statements will provide further guidance to health care professionals and could help improve patient outcomes until a time when good-quality evidence is available.
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8. |
- Chetelat, G., et al.
(författare)
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Amyloid-PET and 18-F-FDG-PET in the diagnostic investigation of Alzheimer's disease and other dementias
- 2020
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Ingår i: Lancet Neurology. - 1474-4422 .- 1474-4465. ; 19:11, s. 951-962
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Forskningsöversikt (refereegranskat)abstract
- Various biomarkers are available to support the diagnosis of neurodegenerative diseases in clinical and research settings. Among the molecular imaging biomarkers, amyloid-PET, which assesses brain amyloid deposition, and F-18-fluorodeoxyglucose (F-18-FDG) PET, which assesses glucose metabolism, provide valuable and complementary information. However, uncertainty remains regarding the optimal timepoint, combination, and an order in which these PET biomarkers should be used in diagnostic evaluations because conclusive evidence is missing. Following an expert panel discussion, we reached an agreement on the specific use of the individual biomarkers, based on available evidence and clinical expertise. We propose a diagnostic algorithm with optimal timepoints for these PET biomarkers, also taking into account evidence from other biomarkers, for early and differential diagnosis of neurodegenerative diseases that can lead to dementia. We propose three main diagnostic pathways with distinct biomarker sequences, in which amyloid-PET and F-18-FDG-PET are placed at different positions in the order of diagnostic evaluations, depending on clinical presentation. We hope that this algorithm can support diagnostic decision making in specialist clinical settings with access to these biomarkers and might stimulate further research towards optimal diagnostic strategies.
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11. |
- Luster, M., et al.
(författare)
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Guidelines for radioiodine therapy of differentiated thyroid cancer
- 2008
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Ingår i: European Journal of Nuclear Medicine and Molecular Imaging. - : Springer Science and Business Media LLC. - 1619-7070 .- 1619-7089. ; 35:10, s. 1941-1959
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Forskningsöversikt (refereegranskat)abstract
- Introduction The purpose of the present guidelines on the radioiodine therapy (RAIT) of differentiated thyroid cancer (DTC) formulated by the European Association of Nuclear Medicine (EANM) Therapy Committee is to provide advice to nuclear medicine clinicians and other members of the DTC-treating community on how to ablate thyroid remnant or treat inoperable advanced DTC or both employing large 131-iodine (I-131) activities. Discussion For this purpose, recommendations have been formulated based on recent literature and expert opinion regarding the rationale, indications and contraindications for these procedures, as well as the radioiodine activities and the administration and patient preparation techniques to be used. Recommendations also are provided on pre-RAIT history and examinations, patient counselling and precautions that should be associated with I-131 iodine ablation and treatment. Furthermore, potential side effects of radioiodine therapy and alternate or additional treatments to this modality are reviewed. Appendices furnish information on dosimetry and post-therapy scintigraphy.
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12. |
- Blom, A M, et al.
(författare)
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Structural characterization of inter-alpha-inhibitor. Evidence for an extended shape
- 1999
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Ingår i: Journal of Biological Chemistry. - 1083-351X. ; 274:1, s. 298-304
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Tidskriftsartikel (refereegranskat)abstract
- Inter-alpha-inhibitor (IalphaI) is a 180-kDa serum protein consisting of three polypeptides. Two of these, the heavy chains 1 and 2 (H1 and H2), are of 75-80 kDa and have similar amino acid sequences. The third polypeptide, bikunin, has a molecular mass of 25 kDa and contains a 7-kDa chondroitin sulfate chain that is covalently linked to the C-terminal amino acid residues of H1 and H2. IalphaI has been shown to be required for the formation of the hyaluronan-containing extracellular matrix of certain cell types. How IalphaI exerts this function is not known, but it appears that upon interaction with cells, the heavy chains are released and become covalently linked to hyaluronan. Our results indicate that IalphaI and its heavy chains are extended molecules; thus, upon electron microscopy, IalphaI appeared to consist of two globular domains connected by a thin structure 31-nm long and the isolated heavy chains of a globular domain and a "tail" about 15-nm long. Analysis of the heavy chains by partial proteolysis showed that the C-terminal halves are particularly sensitive to hydrolysis indicating that they are loosely folded. Furthermore, electron microscopy showed that partially degraded heavy chains lacked the extended regions. Taken together, these results suggest that the N-terminal half of the heavy chains forms a globular domain, whereas the other half has an extended and loosely folded structure.
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13. |
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14. |
- Landsverk, Ole J. B., et al.
(författare)
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Antibody-secreting plasma cells persist for decades in human intestine
- 2017
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Ingår i: Journal of Experimental Medicine. - NewYork, USA : Rockefeller University Press. - 0022-1007 .- 1540-9538. ; 214:2, s. 309-317
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Tidskriftsartikel (refereegranskat)abstract
- Plasma cells (PCs) produce antibodies that mediate immunity after infection or vaccination. In contrast to PCs in the bone marrow, PCs in the gut have been considered short lived. In this study, we studied PC dynamics in the human small intestine by cell-turnover analysis in organ transplants and by retrospective cell birth dating measuring carbon-14 in genomic DNA. We identified three distinct PC subsets: a CD19(+) PC subset was dynamically exchanged, whereas of two CD19(-) PC subsets, CD45(+) PCs exhibited little and CD45(-) PCs no replacement and had a median age of 11 and 22 yr, respectively. Accumulation of CD45(-) PCs during ageing and the presence of rotavirus-specific clones entirely within the CD19(-) PC subsets support selection and maintenance of protective PCs for life in human intestine.
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15. |
- Salgado, Roberto, et al.
(författare)
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Societal challenges of precision medicine : Bringing order to chaos
- 2017
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Ingår i: European Journal of Cancer. - : Elsevier BV. - 0959-8049 .- 1879-0852. ; 84, s. 325-334
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Tidskriftsartikel (refereegranskat)abstract
- The increasing number of drugs targeting specific proteins implicated in tumourigenesis and the commercial promotion of relatively affordable genome-wide analyses has led to an increasing expectation among patients with cancer that they can now receive effective personalised treatment based on the often complex genomic signature of their tumour. For such approaches to work in routine practice, the development of correspondingly complex biomarker assays through an appropriate and rigorous regulatory framework will be required. It is becoming increasingly evident that a re-engineering of clinical research is necessary so that regulatory considerations and procedures facilitate the efficient translation of these required biomarker assays from the discovery setting through to clinical application. This article discusses the practical requirements and challenges of developing such new precision medicine strategies, based on leveraging complex genomic profiles, as discussed at the Innovation and Biomarkers in Cancer Drug Development meeting (8th–9th September 2016, Brussels, Belgium).
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16. |
- Wennergren, Göran, 1947, et al.
(författare)
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The decline in the incidence of SIDS in Scandinavia and its relation to risk-intervention campaigns. Nordic Epidemiological SIDS Study.
- 1997
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Ingår i: Acta paediatrica (Oslo, Norway : 1992). - : Wiley. - 0803-5253 .- 1651-2227. ; 86:9, s. 963-8
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Tidskriftsartikel (refereegranskat)abstract
- A prospective case-control study of sudden infant death syndrome (SIDS) in Norway, Denmark and Sweden between September 1, 1992 and August 31, 1995 comprised 244 cases and 869 matched controls. After the introduction of risk-intervention campaigns, the SIDS incidence decreased from 2.3/1000 live births in Norway, 1.6 in Denmark and 1.0 in Sweden to 0.6/1000 or fewer in all the Scandinavian countries in 1995. The decrease paralleled a decline in the prone sleeping position and there was an accompanying parallel fall in total postneonatal mortality in all three countries. Thus, the risk-reducing campaigns for SIDS have been successful not only in Norway and Denmark, starting from relatively high incidences, but also in Sweden, starting from a low incidence. During the study period, a gradual increase was observed for the effects of prone sleeping, smoking and bottle-feeding as risk factors for SIDS.
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17. |
- Alm, Bernt, 1951, et al.
(författare)
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A case-control study of smoking and sudden infant death syndrome in the Scandinavian countries, 1992 to 1995. The Nordic Epidemiological SIDS Study.
- 1998
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Ingår i: Archives of disease in childhood. - 1468-2044. ; 78:4, s. 329-34
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Tidskriftsartikel (refereegranskat)abstract
- To establish whether smoking is an independent risk factor for sudden infant death syndrome (SIDS), if the effect is mainly due to prenatal or postnatal smoking, and the effect of smoking cessation.The analyses were based on data from the Nordic epidemiological SIDS study, a case-control study with 244 cases and 869 controls. Odds ratios were computed by conditional logistic regression analysis.Smoking emerged as an independent risk factor for SIDS, and the effect was mainly mediated through maternal smoking in pregnancy (crude odds ratio 4.0 (95% confidence interval 2.9 to 5.6)). Maternal smoking showed a marked dose-response relation. There was no effect of paternal smoking if the mother did not smoke. Stopping or even reducing smoking was beneficial. SIDS cases exposed to tobacco smoke were breast fed for a shorter time than non-exposed cases, and feeding difficulties were also more common.Smoking is an independent risk factor for SIDS and is mainly mediated through maternal smoking during pregnancy. Stopping smoking or smoking less may be beneficial in reducing the risk of SIDS.
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18. |
- Alm, Bernt, 1951, et al.
(författare)
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Caffeine and alcohol as risk factors for sudden infant death syndrome. Nordic Epidemiological SIDS Study.
- 1999
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Ingår i: Archives of disease in childhood. - : BMJ. - 1468-2044 .- 0003-9888. ; 81:2, s. 107-11
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Tidskriftsartikel (refereegranskat)abstract
- To assess whether alcohol and caffeine are independent risk factors for sudden infant death syndrome (SIDS).Analyses based on data from the Nordic epidemiological SIDS study, a case control study in which all parents of SIDS victims in the Nordic countries from 1 September 1992 to 31 August 1995 were invited to participate with parents of four controls, matched for sex and age at death. Odds ratios (ORs) were calculated by conditional logistic regression analysis.The crude ORs for caffeine consumption > 800 mg/24 hours both during and after pregnancy were significantly raised: 3.9 (95% confidence interval (CI), 1.9 to 8.1) and 3.1 (95% CI, 1.5 to 6.3), respectively. However, after adjustment for maternal smoking in 1st trimester, maternal age, education and parity, no significant effect of caffeine during or after pregnancy remained. For maternal or paternal alcohol use, no significant risk increase was found after adjusting for social variables, except for heavy postnatal intake of alcohol by the mother, where the risk was significantly increased.Caffeine during or after pregnancy was not found to be an independent risk factor for SIDS after adjustment for maternal age, education, parity, and smoking during pregnancy. Heavy postnatal but not prenatal intake of alcohol by the mother increased the risk.
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19. |
- Brans, B., et al.
(författare)
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Clinical radionuclide therapy dosimetry: the quest for the "Holy Gray"
- 2007
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Ingår i: European Journal of Nuclear Medicine and Molecular Imaging. - : Springer Science and Business Media LLC. - 1619-7070 .- 1619-7089. ; 34:5, s. 772-786
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Forskningsöversikt (refereegranskat)abstract
- Introduction Radionuclide therapy has distinct similarities to, but also profound differences from external radiotherapy. Review This review discusses techniques and results of previously developed dosimetry methods in thyroid carcinoma, neuro-endocrine tumours, solid tumours and lymphoma. In each case, emphasis is placed on the level of evidence and practical applicability. Although dosimetry has been of enormous value in the preclinical phase of radiopharmaceutical development, its clinical use to optimise administered activity on an individual patient basis has been less evident. In phase I and II trials, dosimetry may be considered an inherent part of therapy to establish the maximum tolerated dose and dose-response relationship. To prove that dosimetry-based radionuclide therapy is of additional benefit over fixed dosing or dosing per kilogram body weight, prospective randomised phase III trials with appropriate end points have to be undertaken. Data in the literature which underscore the potential of dosimetry to avoid under- and overdosing and to standardise radionuclide therapy methods internationally are very scarce. Developments In each section, particular developments and insights into these therapies are related to opportunities for dosimetry. The recent developments in PET and PET/CT imaging, including micro-devices for animal research, and molecular medicine provide major challenges for innovative therapy and dosimetry techniques. Furthermore, the increasing scientific interest in the radiobiological features specific to radionuclide therapy will advance our ability to administer this treatment modality optimally.
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20. |
- Christiansen, M, et al.
(författare)
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Mutations in the HERG K+-Ion channel: A novel link between long QT syndrome and sudden infant death syndrome
- 2005
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Ingår i: American Journal of Cardiology. - : Elsevier BV. - 1879-1913 .- 0002-9149. ; 95:3, s. 433-434
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Tidskriftsartikel (refereegranskat)abstract
- In a 7-week-old infant who experienced sudden infant death syndrome (SIDS), a novel missense mutation was identified in KCNH2, causing a lysine-to-glutamic acid amino acid substitution at position 101 (K101E). KCNH2 codes for the HERG ion channel and mutations in the gene are associated with congenital long-QT syndrome (LQTS), and in the family of this case of SIDS, the mutation was associated with Torsades de pointes tachycardia, making SIDS the most likely outcome of congenital LQTS.
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21. |
- Daltveit, A K, et al.
(författare)
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Circadian variations in sudden infant death syndrome: associations with maternal smoking, sleeping position and infections. The Nordic Epidemiological SIDS Study.
- 2003
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Ingår i: Acta paediatrica (Oslo, Norway : 1992). - 0803-5253. ; 92:9, s. 1007-13
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Tidskriftsartikel (refereegranskat)abstract
- To study circadian variation in the sudden infant death syndrome (SIDS) and possible associations with risk factors for SIDS.A questionnaire-based case-control study matched for place of birth, age and gender was conducted in Denmark, Norway and Sweden: The Nordic Epidemiological SIDS Study. The study comprised 244 SIDS victims and 869 control infants between September 1992 and August 1995. The main outcome was hour found dead.A significant circadian pattern was observed among the 242 SIDS victims with a known hour found dead, with a peak at 08.00-08.59 in the morning (n = 33). Of the SIDS victims, 12% were found dead at 00.00-05.59, 58% at 06.00-11.59, 21% at 12.00-17.59 and 9.0% at 18.00-23.59. When comparing night/morning SIDS and day/evening SIDS (found dead 00.00-11.59 and 12.00-23.59, respectively), the proportion of night/morning SIDS was high among infants of smoking mothers (81% vs 53%, p < 0.001), infants with a reported cold (82% vs 64%, p = 0.007) and infants sleeping side/supine (81% vs 60%, p < 0.001). No associations were observed between hour found dead and other sociodemographic risk factors for SIDS. Risk (odds ratio and 95% confidence interval) of night/morning SIDS and day/evening SIDS was 7.0 (4.5-10.9) and 1.5 (0.8-2.5), respectively, for maternal smoking, 2.2 (1.5-3.1) and 0.6 (0.3-1.3), respectively, if the infant had a reported cold, 3.7 (2.1-6.6) and 3.1 (1.1-8.4), respectively, if the infant was put to sleep in the side position (supine reference), and 11.0 (5.9-20.2) and 21.6 (7.6-60.8), respectively, if the infant was put to sleep in the prone position.The observed higher proportion of night/morning cases in SIDS if the mother smoked, if the infant was reported to have a cold and if the infant was sleeping side/supine may contribute to the understanding of some epidemiological characteristics of SIDS.
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22. |
- Daltveit, A K, et al.
(författare)
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Sociodemographic risk factors for sudden infant death syndrome: associations with other risk factors. The Nordic Epidemiological SIDS Study.
- 1998
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Ingår i: Acta paediatrica (Oslo, Norway : 1992). - 0803-5253. ; 87:3, s. 284-90
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Tidskriftsartikel (refereegranskat)abstract
- The aim of this study was to investigate associations between sudden infant death syndrome (SIDS) and social factors in the Nordic countries. A case-control study was conducted in Denmark, Norway and Sweden: The Nordic Epidemiological SIDS Study. Parents of 244 SIDS infants and 869 control infants matched on gender, age at death and place of birth filled in questionnaires. The dataset was analysed by conditional logistic regression. In univariate analysis, the following sociodemographic factors were associated with an increased risk of SIDS: low maternal age [odds ratio (OR) 7.8; 2.8-21.5], high birth order (OR 4.4; 2.5-7.5), single motherhood (OR 2.9; 1.7-5.0), low maternal education (OR 4.5; 2.8-7.1), low paternal education (OR 3.0; 1.9-4.7), maternal unemployment (OR 2.4; 1.8-3.4) and paternal unemployment (OR 4.0; 2.7-5.9). In a multivariate analysis where maternal smoking was also included, only paternal unemployment, young maternal age and high birth order remained significantly associated with SIDS. Housing conditions were not associated with SIDS. However, the risk of SIDS was high if the family had lived in their present home for only a few years (OR 2.3; 1.3-4.1). Sociodemographic differences remain a major concern in SIDS in a low-incidence situation and even in an affluent population with adequate health services.
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23. |
- Fanti, Stefano, et al.
(författare)
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EAU-EANM Consensus Statements on the Role of Prostate-specific Membrane Antigen Positron Emission Tomography/Computed Tomography in Patients with Prostate Cancer and with Respect to [177Lu]Lu-PSMA Radioligand Therapy
- 2022
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Ingår i: European Urology Oncology. - : Elsevier BV. - 2588-9311. ; 5:5, s. 530-536
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Prostate-specific membrane antigen (PSMA) positron emission tomography (PET)/computed tomography (CT) is useful for selected clinical indications in patients with prostate cancer (PCa) but it may have broader clinical utility owing to the emergence of lutetium-177-PSMA-617 ([177Lu]Lu-PSMA) therapy. However, robust data regarding the impact of PSMA PET/CT on patient management and treatment are lacking, and in many areas, the role of next-generation imaging has not been defined. OBJECTIVE: To assess expert opinion on the use of PSMA-based imaging and therapy to develop interim guidance. DESIGN, SETTING, AND PARTICIPANTS: A panel of 21 PCa experts from various disciplines received thematic topics and relevant literature. A questionnaire to assess proposed guidance statements regarding PSMA PET/CT and [177Lu]Lu-PSMA therapy was developed for completion remotely in a first e-Delphi round. A subsequent panel discussion was conducted during a 1-d meeting, which included a second Delphi round. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Panellists voted anonymously on statements using a nine-point Likert scale from 1 = strongly disagree to 9 = strongly agree. Median scores were calculated and consensus was assessed using methods proposed by the Research and Development (RAND) corporation. RESULTS AND LIMITATIONS: Statements were developed to cover the following topics: PSMA PET/CT utility, clinical use, and choice of tracer; patient selection; and management of patients receiving [177Lu]Lu-PSMA for metastatic PCa. Consensus was reached for 33/36 statements. In-group bias is a potential limitation, as some statements were rephrased during discussions at the 1-d meeting. CONCLUSIONS: Adoption of PSMA PET/CT as an imaging tool to guide [177Lu]Lu-PSMA therapy should be supported by indications for appropriate use. PATIENT SUMMARY: A panel of experts in prostate cancer reached a consensus for the majority of statements proposed regarding the role of prostate-specific membrane antigen (PSMA)-based imaging and therapy, particularly the use of PSMA-based imaging in patients suitable for [177Lu]Lu-PSMA therapy and the need to perform PSMA-based imaging before considering patients as candidates for this therapy.
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24. |
- Helweg-Larsen, K, et al.
(författare)
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Interactions of infectious symptoms and modifiable risk factors in sudden infant death syndrome. The Nordic Epidemiological SIDS study.
- 1999
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Ingår i: Acta paediatrica (Oslo, Norway : 1992). - 0803-5253. ; 88:5, s. 521-7
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Tidskriftsartikel (refereegranskat)abstract
- The aim of the study was to investigate the effect of infection on sudden infant death syndrome (SIDS) and to analyse whether modifiable risk factors of SIDS, prone sleeping, covered head and smoking act as effect modifiers. In a consecutive multicentre case-control study of SIDS in Denmark, Norway and Sweden, questionnaires on potential risk factors for SIDS were completed by parents of SIDS victims, and for at least two controls matched for gender, age and place of birth. All SIDS cases were verified by an autopsy. The study comprised 244 SIDS cases and 869 controls, analysed by conditional logistic regression. Significantly more cases than controls presenting symptoms of infectious diseases during the last week and/or last day were treated with antibiotics and had been seen by a physician. The finding is consistent with the hypothesis of an infectious mechanism in SIDS induced by local microorganism growth and toxin or cytokine production, and also adds further support to a possible association between infection and SIDS by loss of protective mechanisms, such as arousal. The risk of SIDS among infants with the combined presence of infectious symptoms and either of the other modifiable risk factors, prone sleeping, head covered or parental smoking, was far greater than the sum of each individual factor. These risk factors thus modify the dangerousness of infection in infancy.
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25. |
- Heskamp, Sandra, et al.
(författare)
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Imaging of Human Epidermal Growth Factor Receptor Type 2 Expression with (18)F-Labeled Affibody Molecule Z(HER2:2395) in a Mouse Model for Ovarian Cancer
- 2012
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Ingår i: Journal of Nuclear Medicine. - : Society of Nuclear Medicine. - 0161-5505 .- 1535-5667 .- 2159-662X. ; 53:1, s. 146-153
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Tidskriftsartikel (refereegranskat)abstract
- Affibody molecules are small (7 kDa) proteins with subnanomolar targeting affinity. Previous SPECT studies in xenografts have shown that the Affibody molecule (111)In-DOTA-Z(HER2:2395) can discriminate between high and low human epidermal growth factor receptor type 2 (HER2)-expressing tumors, indicating that radiolabeled Affibody molecules have potential for patient selection for HER2-targeted therapy. Compared with SPECT, PET with positron-emitting radionuclides, such as (18)F, may improve imaging of HER2 expression because of higher sensitivity and improved quantification of PET. The aim of the present study was to determine whether the (18)F-labeled NOTA-conjugated Affibody molecule Z(HER2:2395) is a suitable agent for imaging of HER2 expression. The tumor-targeting properties of (18)F-labeled Z(HER2:2395) were compared with (111)In- and (68)Ga-labeled Z(HER2:2395) in mice with HER2-expressing SK-OV-3 xenografts. Methods: Z(HER2:2395) was conjugated with NOTA and radiolabeled with (18)F, (68)Ga, and (111)In. Radiolabeling with (18)F was based on the complexation of Al(18)F by NOTA. The 50% inhibitory concentration values for NOTA-Z(HER2:2395) labeled with (19)F, (69)Ga, and (115)In were determined in a competitive cell-binding assay using SK-OV-3 cells. Mice bearing subcutaneous SK-OV-3 xenografts were injected intravenously with radiolabeled NOTA-Z(HER2:2395). One and 4 h after injection, PET/CT or SPECT/CT images were acquired, and the biodistribution was determined by ex vivo measurement. Results: The 50% inhibitory concentration values for (19)F-, (69)Ga-, and (115)In-NOTA-Z(HER2:2395) were 5.0, 6.3, and 5.3 nM, respectively. One hour after injection, tumor uptake was 4.4 +/- 0.8 percentage injected dose per gram (% ID/g), 5.6 +/- 1.6 % ID/g, and 7.1 +/- 1.4 % ID/g for (18)F-, (68)Ga-, and (111)In-NOTA-Z(HER2:2395), respectively, and the respective tumor-to-blood ratios were 7.4 +/- 1.8, 8.0 +/- 1.3, and 4.8 +/- 1.3. Tumor uptake was specific, because uptake could be blocked efficiently by coinjection of an excess of unlabeled Z(HER2:2395). PET/CT and SPECT/CT images clearly visualized HER2-expressing SK-OV-3 xenografts. Conclusion: This study showed that (18)F-NOTA-Z(HER2:2395) is a promising new imaging agent for HER2 expression in tumors. Affibody molecules were successfully labeled with (18)F within 30 min, based on the complexation of Al(18)F by NOTA. Further research is needed to determine whether this technique can be used for patient selection for HER2-targeted therapy.
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