| 1. |
- Bentham, James, et al.
(författare)
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A century of trends in adult human height
- 2016
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Ingår i: eLIFE. - 2050-084X. ; 5
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Tidskriftsartikel (refereegranskat)abstract
- Being taller is associated with enhanced longevity, and higher education and earnings. We reanalysed 1472 population-based studies, with measurement of height on more than 18.6 million participants to estimate mean height for people born between 1896 and 1996 in 200 countries. The largest gain in adult height over the past century has occurred in South Korean women and Iranian men, who became 20.2 cm (95% credible interval 17.522.7) and 16.5 cm (13.319.7) taller, respectively. In contrast, there was little change in adult height in some sub-Saharan African countries and in South Asia over the century of analysis. The tallest people over these 100 years are men born in the Netherlands in the last quarter of 20th century, whose average heights surpassed 182.5 cm, and the shortest were women born in Guatemala in 1896 (140.3 cm; 135.8144.8). The height differential between the tallest and shortest populations was 19-20 cm a century ago, and has remained the same for women and increased for men a century later despite substantial changes in the ranking of countries.
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| 2. |
- Bentham, James, et al.
(författare)
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A century of trends in adult human height
- 2016
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Ingår i: eLIFE. - : eLife Sciences Publications Ltd. - 2050-084X. ; 5
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Tidskriftsartikel (refereegranskat)abstract
- Being taller is associated with enhanced longevity, and higher education and earnings. We reanalysed 1472 population-based studies, with measurement of height on more than 18.6 million participants to estimate mean height for people born between 1896 and 1996 in 200 countries. The largest gain in adult height over the past century has occurred in South Korean women and Iranian men, who became 20.2 cm (95% credible interval 17.5–22.7) and 16.5 cm (13.3– 19.7) taller, respectively. In contrast, there was little change in adult height in some sub-Saharan African countries and in South Asia over the century of analysis. The tallest people over these 100 years are men born in the Netherlands in the last quarter of 20th century, whose average heights surpassed 182.5 cm, and the shortest were women born in Guatemala in 1896 (140.3 cm; 135.8– 144.8). The height differential between the tallest and shortest populations was 19-20 cm a century ago, and has remained the same for women and increased for men a century later despite substantial changes in the ranking of countries.
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| 3. |
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| 4. |
- Bracci-Laudiero, Luisa, et al.
(författare)
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NGF modulates CGRP synthesis in human B-lymphocytes : A possible anti-inflammatory action of NGF?
- 2002
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Ingår i: Journal of Neuroimmunology. - 0165-5728 .- 1872-8421. ; 123:1-2, s. 58-65
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Tidskriftsartikel (refereegranskat)abstract
- We investigated whether the sensory neuropeptide, calcitonin gene-related peptide (CGRP), could be synthesised by human lymphocytes. Our results indicate that in activated B-cells, there is a strong expression of CGRP gene transcripts, which is almost absent in resting cells. Since B-cells autocrinally produce NGF, the neutralisation of endogenous NGF by anti-NGF antibodies resulted in a marked reduction in CGRP expression in both resting and activated B-cells. Thus, NGF appears to directly affect the synthesis of CGRP in B-cells as in sensory neurons. By regulating CGRP synthesis in lymphocytes and neuronal cells, NGF can influence the intensity and duration of the immune response. ⌐ 2002 Elsevier Science B.V. All rights reserved.
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| 5. |
- Cortes, Dina, et al.
(författare)
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A new model of paired clinical teaching of international and Danish medical students
- 2016
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Ingår i: Danish Medical Journal. - 2245-1919. ; 63:7, s. 1-5
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Tidskriftsartikel (refereegranskat)abstract
- INTRODUCTION: Since 2006, one hospital has offered two clinical courses in obstetrics/gynaecology and paediatrics to international (I) students. However, as I-student enrolment increased, the hospital faced cut-backs. As from 2010, I-team course evaluations therefore dropped to unacceptable levels and more I- than Danish (DK) students failed exams. Therefore, in 2012 we started a three-year internationalisation project (I-project) at two hospitals. The primary intervention was to pair training for I- and DK-students at clinical contact, and to offer an exclusive daily lecturer for I-teams.METHODS: We compared the course evaluations and exam grades of I-teams and DK-teams for two years prior to (107 from I-teams - 211 participants from DK-teams) and during the I-project (245 participants from I-teams - 575 from DK-teams).RESULTS: During the I-project, the I-teams' course evaluations increased to acceptable values and to levels comparable to the evaluation scores of DK-teams. Furthermore, I-students now considered that their communication with the patients was acceptable. Before the I-project, I-students had lower exam grades (median = 10 (range: 0-12)) than DK-students (10 (4-12)) (p = 0.03), but during the I-project, exam grades increased to the levels achieved by DK-students (10 (2-12) - 10 (0-12) (p = 0.22), and no more I- than DK-students failed exams (p = 0.51).CONCLUSIONS: Pairing students for clinical training and allocating an exclusive lecturer for I-teams produced improved courses for internationalisation. Allocating an exclusive lecturer was associated with a cost of about 615 EUR per student per course when the team consisted of ten students.FUNDING: The Capital Region of Denmark and the University of Copenhagen.TRIAL REGISTRATION: not relevant.
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| 6. |
- Finn, Anja
(författare)
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Biochemical biomarkers at the site of inflammation and in peripheral blood
- 2015
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Biochemical biomarkers are small molecular species, naturally varying or experimentally induced, which are measurable in body fluids and which may provide alternative or complementary tools to describe disease processes or to assess responses to pharmacological treatment. The focus of this thesis is inflammatory biomarkers, mediators, chemokines and cytokines that attract immune cells and that regulate the course of the inflammatory process at the site of inflammation. A major objective was to evaluate the behavior of these molecules in blood. In the first study we used two established animal models, the Freund´s Complete Adjuvant (FCA) model and the Carrageenan model, to induce experimental inflammation in rats and could demonstrate a significant decrease of prostaglandin E2 (PGE2) in synovial fluid following treatment with two COX-inhibitors, naproxen and rofecoxib, despite the drugs having limited efficacy on overall joint swelling. L(+)-lactate, the end product of glycolysis, reflects cell activity and was therefore hypothesized to be a suitable novel indicator of experimental inflammation. We found that L(+)-lactate levels were unaffected by COX-inhibitors in this study, indicating that L(+)-lactate might be used as a biochemical biomarker for on-going inflammation in individuals being treated with COX-inhibitors. In the next study we therefore assessed levels of L(+)-lactate, as well as chemokines and cytokines, in joint fluids from human osteoarthritis patients and in an additional animal model, the monoiodo acetate (MIA) model, which primarily induces cartilage degradation, osteophyte formation and mild synovitis. MIA induced distinct inflammatory biomarkers in a biphasic manner, but in considerably lower amounts than FCA, suggesting that the underlying pathology in these two models is significantly different. As expected, L(+)-lactate was readily detectable in synovial fluid in the MIA model and in humans, correlating with the levels of cytokines and chemokines, and thereby indicating the presence of inflammatory cells in the joint cavity. We also observed two common findings between the MIA model and in humans, namely the presence of IL-6 in joint and serum and the lack of IL-1β and TNF in the same matrices. Nevertheless, we found it difficult to identify a single systemic biochemical biomarker that specifically reflects an ongoing local inflammatory process in osteoarthritis, and nor was it possible to identify a specific translational biomarker between the animal models and OA individuals. In the third study, in rats subjected to spinal cord injury, the main findings were changes in inflammatory biomarkers in serum during the time of treatment with the drug imatinib, a tyrosine kinase inhibitor. Although serum levels of MCP-1 and MIP-3α were increased at day 1 following injury or sham injury, levels remained similar or lower throughout the study up to 7 days whereas MCP-1 and MIP-3α were further increased at 7 days following injury in the imatinib group. It is plausible that our findings will translate to humans and that the SCI individual could be its own control. Nerve Growth Factor (NGF) is released following tissue injury and therefore the aim was to determine whether NGF is released into the synovial fluid in the FCA model. In the last study we reported the successful development of an assay for the measurement of rat NGF in synovial fluid in rats exposed to FCA. We conclude that the usage of biochemical biomarkers has wide application, and may be used as a complementary tool to other readouts for the analysis of inflammatory conditions.
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| 7. |
- Finn, Anja
(författare)
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Methods and detection of endogenous peptides in the CNS and GI tract
- 2006
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Licentiatavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Endogenous peptides, such as enkephalins, endorphins and orexins modulate a variety of biological processes; these peptides are found in the central nervous system and periphery, including the gastrointestinal tract. One of the methods commonly used to determine localization, concentration, expression and function of endogenous peptides is the radio immunoassay (RIA). A critical part of the RIA is the choice of antibodies, which are the specific tools to enable measurement of peptides. The outcome of a neuropeptide RIA depends on several aspects of the experimental setting such as age, gender, species, diurnal rhythm or environmental stress. The aims for the studies (paper I and II) were production of antisera using peptide conjugates for the specific neuropeptides, niethmethionine-enkephalin-Arg6-Phe7 (MEAP) and rat P-endorphin and the antibodies were further characterized. Specific aims were to clarify some of the differences between art-specific antibodies and the outcome of α-endorphin RIAs. Furthermore, levels of MEAP and α-endorphin were detected in specific brain areas (hypothalamus and periaqueductal grey) and peripheral tissue of rats. Finally, to further understand the role of orexins in the gut: we investigated circulating concentrations of orexin A in human plasma with an optimized RIA (paper III). Optimization of the neuropeptide RIAs was mainly done by a careful selection of the most optimal included components, i.e. the use of spec ies-specific standards and antibodies. The response to the immunization varied between rabbits from poor to exceptional (MEAP ab 4108). Two antisera from each group (MEAP and α-endorphin) showed useful titres, sensitivity, avidity and specificity and RIAs were set up. When using the MEAP antibody 4108, the relative levels of immunoreactive material from rats were verified due to current knowledge. In the case of α-endorphin, the RIA outcome was not optimal when using nonspecies compatible components when analysing rat hypothalamus tissue. The rat antibody allowed for larger detection range and specificity. No significant changes were observed in either the hypothalamus or periaqueductal grey of rats, when using the new rat α-endorphin antibodies to investigate the effects of diurnal variation or environmental stress. Concentrations of human plasma levels of circulating orexin A verified untreated levels and enabled to monitor increasing concentrations by time after addition of exogenous orexin A. The present work illustrates the importance of understanding the RIA technique for its proper evaluation and determination of tissue- and plasma concentrations. Selection of an appropriate antibody is essential, therefore its characteristics has to be investigated.
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| 8. |
- Hollestelle, Antoinette, et al.
(författare)
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No clinical utility of KRAS variant rs61764370 for ovarian or breast cancer
- 2016
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Ingår i: Gynecologic Oncology. - : Elsevier BV. - 0090-8258 .- 1095-6859. ; 141:2, s. 386-401
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Tidskriftsartikel (refereegranskat)abstract
- Objective Clinical genetic testing is commercially available for rs61764370, an inherited variant residing in a KRAS 3′ UTR microRNA binding site, based on suggested associations with increased ovarian and breast cancer risk as well as with survival time. However, prior studies, emphasizing particular subgroups, were relatively small. Therefore, we comprehensively evaluated ovarian and breast cancer risks as well as clinical outcome associated with rs61764370. Methods Centralized genotyping and analysis were performed for 140,012 women enrolled in the Ovarian Cancer Association Consortium (15,357 ovarian cancer patients; 30,816 controls), the Breast Cancer Association Consortium (33,530 breast cancer patients; 37,640 controls), and the Consortium of Modifiers of BRCA1 and BRCA2 (14,765 BRCA1 and 7904 BRCA2 mutation carriers). Results We found no association with risk of ovarian cancer (OR = 0.99, 95% CI 0.94-1.04, p = 0.74) or breast cancer (OR = 0.98, 95% CI 0.94-1.01, p = 0.19) and results were consistent among mutation carriers (BRCA1, ovarian cancer HR = 1.09, 95% CI 0.97-1.23, p = 0.14, breast cancer HR = 1.04, 95% CI 0.97-1.12, p = 0.27; BRCA2, ovarian cancer HR = 0.89, 95% CI 0.71-1.13, p = 0.34, breast cancer HR = 1.06, 95% CI 0.94-1.19, p = 0.35). Null results were also obtained for associations with overall survival following ovarian cancer (HR = 0.94, 95% CI 0.83-1.07, p = 0.38), breast cancer (HR = 0.96, 95% CI 0.87-1.06, p = 0.38), and all other previously-reported associations. Conclusions rs61764370 is not associated with risk of ovarian or breast cancer nor with clinical outcome for patients with these cancers. Therefore, genotyping this variant has no clinical utility related to the prediction or management of these cancers.
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| 9. |
- Jespersen, Gry, et al.
(författare)
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A thiol functionalized cryogel as a solid phase for selective reduction of a cysteine residue in a recombinant human growth hormone variant.
- 2014
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Ingår i: Journal of Biotechnology. - : Elsevier BV. - 1873-4863 .- 0168-1656. ; 173, s. 76-85
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Tidskriftsartikel (refereegranskat)abstract
- Site selective chemical modification is a preferred method, employed to prolong the circulation half-life of biopharmaceuticals. Cysteines have been used as attachment point for such modification, however, to be susceptible for chemical modification the involved thiol must be in its reduced form. Proteins often contain disulfides, which aid to maintain their tertiary structure and therefore must remain intact. Thus, methods for selectively reducing cysteine residues, introduced through site-directed mutagenesis, are of interest. In this study a macroporous, polymeric monolith was designed for selectively reducing a single cysteine residue inserted in recombinant human growth hormone (hGH). Advantages of such a material are the circumvention of the need to remove the reducing agent after reaction, as well as milder reduction conditions and a concomitant lower risk of reducing the native disulfides. The designed monolith showed very high capacity towards the selective reduction of an unpaired cysteine residue in a recombinant hGH variant. Factors influencing the selectivity and rate of reaction were investigated and it was found that monolith thiol loading, and buffer pH had an effect on the rate of reduction, whereas hGH variant concentration and buffer conductivity influenced both rate of reduction and selectivity. The developed system constitutes the basis for the development of a scalable platform for selective reduction of a capped cysteine residue in hGH.
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| 10. |
- Kehoe, Laura, et al.
(författare)
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Make EU trade with Brazil sustainable
- 2019
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Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 364:6438, s. 341-
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
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| 11. |
- Kläppe, Ulf, et al.
(författare)
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Neurodegenerative biomarkers outperform neuroinflammatory biomarkers in amyotrophic lateral sclerosis.
- 2023
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Ingår i: Amyotrophic lateral sclerosis & frontotemporal degeneration. - 2167-9223. ; 25:1-2, s. 150-61
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Tidskriftsartikel (refereegranskat)abstract
- To describe the diagnostic and prognostic performance, and longitudinal trajectories, of potential biomarkers of neuroaxonal degeneration and neuroinflammation in amyotrophic lateral sclerosis (ALS).This case-control study included 192 incident ALS patients, 42 ALS mimics, 114 neurological controls, and 117 healthy controls from Stockholm, Sweden. Forty-four ALS patients provided repeated measurements. We assessed biomarkers of (1)neuroaxonal degeneration: neurofilament light (NfL) and phosphorylated neurofilament heavy (pNfH) in cerebrospinal fluid (CSF) and NfL in serum, and (2)neuroinflammation: chitotriosidase-1 (CHIT1) and monocyte chemoattractant protein 1 (MCP-1) in CSF. To evaluate diagnostic performance, we calculated the area under the curve (AUC). To estimate prognostic performance, we applied quantile regression and Cox regression. We used linear regression models with robust standard errors to assess temporal changes over time.Neurofilaments performed better at differentiating ALS patients from mimics (AUC: pNfH 0.92, CSF NfL 0.86, serum NfL 0.91) than neuroinflammatory biomarkers (AUC: CHIT1 0.71, MCP-1 0.56). Combining biomarkers did not improve diagnostic performance. Similarly, neurofilaments performed better than neuroinflammatory biomarkers at predicting functional decline and survival. The stratified analysis revealed differences according to the site of onset: in bulbar patients, neurofilaments and CHIT1 performed worse at predicting survival and correlations were lower between biomarkers. Finally, in bulbar patients, neurofilaments and CHIT1 increased longitudinally but were stable in spinal patients.Biomarkers of neuroaxonal degeneration displayed better diagnostic and prognostic value compared with neuroinflammatory biomarkers. However, in contrast to spinal patients, in bulbar patients neurofilaments and CHIT1 performed worse at predicting survival and seemed to increase over time.
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| 12. |
- Kosek, Eva, et al.
(författare)
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Evidence of different mediators of central inflammation in dysfunctional and inflammatory pain--interleukin-8 in fibromyalgia and interleukin-1 β in rheumatoid arthritis.
- 2015
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Ingår i: Journal of Neuroimmunology. - : Elsevier BV. - 0165-5728 .- 1872-8421. ; 280, s. 49-55
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Tidskriftsartikel (refereegranskat)abstract
- The purpose of this study was to relate central inflammation to autonomic activity (heart rate variability (HRV)) in patients with rheumatoid arthritis (RA) and fibromyalgia (FM). RA patients had reduced parasympathetic activity and FM patients had increased sympathetic activity compared to healthy controls. Comparisons between RA and FM showed higher cerebrospinal fluid (CSF) interleukin (IL)-1β inversely correlated to parasympathetic activity in RA. The FM patients had higher concentrations of CSF IL-8, IL-1Ra, IL-4 and IL-10, but none of these cytokines correlated with HRV. In conclusion, we found different profiles of central cytokines, i.e., elevated IL-1β in inflammatory pain (RA) and elevated IL-8 in dysfunctional pain (FM).
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| 13. |
- Moller, Kristina Angeby, et al.
(författare)
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Using gait analysis to assess weight bearing in rats with Freund's complete adjuvant-induced monoarthritis to improve predictivity : Interfering with the cyclooxygenase and nerve growth factor pathways
- 2015
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Ingår i: European Journal of Pharmacology. - : Elsevier BV. - 0014-2999 .- 1879-0712. ; 756, s. 75-84
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Tidskriftsartikel (refereegranskat)abstract
- Lack of predictive power for drug effects has been a major criticism against animal pain models. It is therefore important to define the utility and limitations of different models. The aim of this study was to extend previous work on gait analysis as a tool to investigate pharmacological effects in monoarthritic rats, specifically to test the hypothesis that monoarthritis induced by Freund's complete adjuvant (FCA) provides a better estimate of overall analgesic efficacy of established, and novel, clinically effective and ineffective therapeutic approaches. Male rats injected intra-articularly into one ankle joint with FCA (1.0mg/ml) were treated with the monoclonal antibody to nerve growth factor (NGF), MEDI-578, the inhibitors of tropomyosin receptor kinases A, B and C (pan-Trk) AZ6623 or AZ7092, the transient receptor potential vanilloid 1 (TRPV1) inhibitor AZD1386, or the cyclooxygenase (COX) inhibitors naproxen, ibuprofen, valdecoxib or rofecoxib. Effects on weight bearing during locomotion were tested using video capture of print images. The apparent efficacy in this model was Trk inhibitors >= anti-NGF antibody > COX inhibitors. The TRPV1 inhibitor was ineffective. Together with previous data, the results support using gait-related parameters in the monoarthritis model. FCA as induction agent seems to provide a good overall prediction of analgesic efficacy in disorders with inflammatory joint pain. (C) 2015 Elsevier B.V. All rights reserved.
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| 14. |
- Palada, Vinko, et al.
(författare)
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Characterization of neuroinflammation and periphery-to-CNS inflammatory cross-talk in patients with disc herniation and degenerative disc disease.
- 2019
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Ingår i: Brain, behavior, and immunity. - : Elsevier BV. - 0889-1591 .- 1090-2139. ; 75, s. 60-71
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Tidskriftsartikel (refereegranskat)abstract
- The aim of the study was to identify inflammatory cytokines/chemokines associated with neuroinflammation and periphery-to-CNS inflammatory cross-talk in degenerative disc disease (DDD) and lumbar disc herniation (LDH), common causes of low back pain (LBP). A secondary aim was to investigate the associations between cytokines and symptom severity.METHODS: In total, 40 DDD and 40 LDH patients were recruited from a surgical waiting list, as well as 39 healthy controls (HC) and 40 cerebrospinal fluid (CSF) controls. The subjects completed questionnaires and pressure algometry was performed at the lumbar spine and forearm. The CSF, serum and disc tissues were collected during surgery. Inflammatory mediators TNF, INFg, IL-1b, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12p70, IL-13 and MCP1 were analysed by immunoassay (Meso Scale Discovery) and quantitative real-time polymerase chain reaction (qPCR) was used for analysis of IL-6, IL-8, MCP1 and TSPO expression in intervertebral discs (IVDs).RESULTS: In the LDH group, we found elevated IL-8 concentrations in CSF indicating neuroinflammation, while IL-8 and MCP1 concentrations in serum were lower compared to HC. The IVD expression of IL-6, IL-8 and TSPO was lower in LDH patients compared to DDD. LDH patients had a positive correlation between IL-8 concentrations in CSF and serum and IL-8 in CSF was associated with higher pain intensity and increased spinal pressure pain sensitivity. The MCP1 concentration in serum was associated with higher global pain ratings and increased spinal pressure pain sensitivity, while IL-6 serum concentration correlated with the intensity of the neuropathic pain component (leg pain) in LDH patients. IVD expression of TSPO in LDH patients was associated with increased intensity of back pain. No differences were found in cytokine CSF concentrations between DDD patients and CSF controls, but DDD patients had lower IL-8 and MCP1 serum concentrations than HC. In female DDD patients, IL-8 and MCP1 concentrations in serum were associated with increased intensity of back pain.CONCLUSION: Our results suggest that neuroinflammation mediated by elevated IL-8 concentrations in CSF and IL-8 mediated periphery-to-CNS inflammatory cross-talk contributes to pain in LDH patients and suggest a link between TSPO expression in discs and low back pain.
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| 15. |
- Schwieler, Lilly, et al.
(författare)
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Increased levels of IL-6 in the cerebrospinal fluid of patients with chronic schizophrenia - significance for activation of the kynurenine pathway.
- 2015
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Ingår i: Journal of Psychiatry & Neuroscience. - : CMA-CANADIAN MEDICAL ASSOC. - 1180-4882 .- 1488-2434. ; 40:2, s. 126-13
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Accumulating evidence indicates that schizophrenia is associated with brain immune activation. While a number of reports suggest increased cytokine levels in patients with schizophrenia, many of these studies have been limited by their focus on peripheral cytokines or confounded by various antipsychotic treatments. Here, well-characterized patients with schizophrenia, all receiving olanzapine treatment, and healthy volunteers were analyzed with regard to cerebrospinal fluid (CSF) levels of cytokines. We correlated the CSF cytokine levels to previously analyzed metabolites of the kynurenine (KYN) pathway.METHODS: We analyzed the CSF from patients and controls using electrochemiluminescence detection with regard to cytokines. Cell culture media from human cortical astrocytes were analyzed for KYN and kynurenic acid (KYNA) using high-pressure liquid chromatography or liquid chromatography/mass spectrometry.RESULTS: We included 23 patients and 37 controls in our study. Patients with schizophrenia had increased CSF levels of interleukin (IL)-6 compared with healthy volunteers. In patients, we also observed a positive correlation between IL-6 and the tryptophan:KYNA ratio, indicating that IL-6 activates the KYN pathway. In line with this, application of IL-6 to cultured human astrocytes increased cell medium concentration of KYNA.LIMITATIONS: The CSF samples had been frozen and thawed twice before analysis of cytokines. Median age differed between patients and controls. When appropriate, all present analyses were adjusted for age.CONCLUSION: We have shown that IL-6, KYN and KYNA are elevated in patients with chronic schizophrenia, strengthening the idea of brain immune activation in patients with this disease. Our concurrent cell culture and clinical findings suggest that IL-6 induces the KYN pathway, leading to increased production of the N-methyl-D-aspartate receptor antagonist KYNA in patients with schizophrenia.
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| 16. |
- Winther, Jeanete F., et al.
(författare)
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Childhood cancer survivor cohorts in Europe
- 2015
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Ingår i: Acta Oncologica. - 1651-226X. ; 54:5, s. 655-668
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Forskningsöversikt (refereegranskat)abstract
- With the advent of multimodality therapy, the overall five-year survival rate from childhood cancer has improved considerably now exceeding 80% in developed European countries. This growing cohort of survivors, with many years of life ahead of them, has raised the necessity for knowledge concerning the risks of adverse long-term sequelae of the life-saving treatments in order to provide optimal screening and care and to identify and provide adequate interventions. Childhood cancer survivor cohorts in Europe. Considerable advantages exist to study late effects in individuals treated for childhood cancer in a European context, including the complementary advantages of large population-based cancer registries and the unrivalled opportunities to study lifetime risks, together with rich and detailed hospital-based cohorts which fill many of the gaps left by the large-scale population-based studies, such as sparse treatment information. Several large national cohorts have been established within Europe to study late effects in individuals treated for childhood cancer including the Nordic Adult Life after Childhood Cancer in Scandinavia study (ALiCCS), the British Childhood Cancer Survivor Study (BCCSS), the Dutch Childhood Oncology Group (DCOG) LATER study, and the Swiss Childhood Cancer Survivor Study (SCCSS). Furthermore, there are other large cohorts, which may eventually become national in scope including the French Childhood Cancer Survivor Study (FCCSS), the French Childhood Cancer Survivor Study for Leukaemia (LEA), and the Italian Study on off-therapy Childhood Cancer Survivors (OTR). In recent years significant steps have been taken to extend these national studies into a larger pan-European context through the establishment of two large consortia - PanCareSurFup and PanCareLIFE. The purpose of this paper is to present an overview of the current large, national and pan-European studies of late effects after childhood cancer. This overview will highlight the strong cooperation across Europe, in particular the EU-funded collaborative research projects PanCareSurFup and PanCareLIFE. Overall goal. The overall goal of these large cohort studies is to provide every European childhood cancer survivor with better care and better long-term health so that they reach their full potential, and to the degree possible, enjoy the same quality of life and opportunities as their peers.
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