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1.
  • Semb, Gunvor, et al. (författare)
  • A Scandcleft randomised trials of primary surgery for unilateral cleft lip and palate: 1. Planning and management.
  • 2017
  • Ingår i: Journal of Plastic Surgery and Hand Surgery. - : Taylor & Francis. - 2000-656X .- 2000-6764. ; 51:1, s. 2-13
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND AND AIMS: Longstanding uncertainty surrounds the selection of surgical protocols for the closure of unilateral cleft lip and palate, and randomised trials have only rarely been performed. This paper is an introduction to three randomised trials of primary surgery for children born with complete unilateral cleft lip and palate (UCLP). It presents the protocol developed for the trials in CONSORT format, and describes the management structure that was developed to achieve the long-term engagement and commitment required to complete the project.METHOD: Ten established national or regional cleft centres participated. Lip and soft palate closure at 3-4 months, and hard palate closure at 12 months served as a common method in each trial. Trial 1 compared this with hard palate closure at 36 months. Trial 2 compared it with lip closure at 3-4 months and hard and soft palate closure at 12 months. Trial 3 compared it with lip and hard palate closure at 3-4 months and soft palate closure at 12 months. The primary outcomes were speech and dentofacial development, with a series of perioperative and longer-term secondary outcomes.RESULTS: Recruitment of 448 infants took place over a 9-year period, with 99.8% subsequent retention at 5 years.CONCLUSION: The series of reports that follow this introductory paper include comparisons at age 5 of surgical outcomes, speech outcomes, measures of dentofacial development and appearance, and parental satisfaction. The outcomes recorded and the numbers analysed for each outcome and time point are described in the series.TRIAL REGISTRATION: ISRCTN29932826.
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2.
  • Andersen, Zorana J., et al. (författare)
  • Long-term Exposure to Ambient Air Pollution and Incidence of Brain Tumor : the European Study of Cohorts for Air Pollution Effects (ESCAPE)
  • 2018
  • Ingår i: Neuro-Oncology. - : Oxford University Press. - 1522-8517 .- 1523-5866. ; 20:3, s. 420-432
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Epidemiological evidence on the association between ambient air pollution and brain tumor risk is sparse and inconsistent.Methods: In 12 cohorts from 6 European countries, individual estimates of annual mean air pollution levels at the baseline residence were estimated by standardized land-use regression models developed within the ESCAPE and TRANSPHORM projects: particulate matter (PM) ≤2.5, ≤10, and 2.5–10 μm in diameter (PM2.5, PM10, and PMcoarse), PM2.5 absorbance, nitrogen oxides (NO2 and NOx) and elemental composition of PM. We estimated cohort-specific associations of air pollutant concentrations and traffic intensity with total, malignant, and nonmalignant brain tumor, in separate Cox regression models, adjusting for risk factors, and pooled cohort-specific estimates using random-effects meta-analyses.Results: Of 282194 subjects from 12 cohorts, 466 developed malignant brain tumors during 12 years of follow-up. Six of the cohorts also had data on nonmalignant brain tumor, where among 106786 subjects, 366 developed brain tumor: 176 nonmalignant and 190 malignant. We found a positive, statistically nonsignificant association between malignant brain tumor and PM2.5 absorbance (hazard ratio and 95% CI: 1.67; 0.89–3.14 per 10–5/m3), and weak positive or null associations with the other pollutants. Hazard ratio for PM2.5 absorbance (1.01; 0.38–2.71 per 10–5/m3) and all other pollutants were lower for nonmalignant than for malignant brain tumors.Conclusion: We found suggestive evidence of an association between long-term exposure to PM2.5 absorbance indicating traffic-related air pollution and malignant brain tumors, and no association with overall or nonmalignant brain tumors.
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3.
  • Andersen, Zorana J., et al. (författare)
  • Long-term exposure to ambient air pollution and incidence of postmenopausal breast cancer in 15 European cohorts within the ESCAPE project
  • 2017
  • Ingår i: Journal of Environmental Health Perspectives. - Research triangle park : US department of health. - 0091-6765 .- 1552-9924. ; 125:10
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Epidemiological evidence on the association between ambient air pollution and breast cancer risk is inconsistent.OBJECTIVE: We examined the association between long-term exposure to ambient air pollution and incidence of postmenopausal breast cancer in European women.METHODS: In 15 cohorts from nine European countries, individual estimates of air pollution levels at the residence were estimated by standardized land-use regression models developed within the European Study of Cohorts for Air Pollution Effects (ESCAPE) and Transport related Air Pollution and Health impacts – Integrated Methodologies for Assessing Particulate Matter (TRANSPHORM) projects: particulate matter (PM) ≤2.5μm, ≤10μm, and 2.5–10μm in diameter (PM2.5, PM10, and PMcoarse, respectively); PM2.5 absorbance; nitrogen oxides (NO2 and NOx); traffic intensity; and elemental composition of PM. We estimated cohort-specific associations between breast cancer and air pollutants using Cox regression models, adjusting for major lifestyle risk factors, and pooled cohort-specific estimates using random-effects meta-analyses.RESULTS: Of 74,750 postmenopausal women included in the study, 3,612 developed breast cancer during 991,353 person-years of follow-up. We found positive and statistically insignificant associations between breast cancer and PM2.5 {hazard ratio (HR)=1.08 [95% confidence interval (CI): 0.77, 1.51] per 5 μg/m(3)}, PM10 [1.07 (95% CI: 0.89, 1.30) per 10 μg/m(3)], PMcoarse[1.20 (95% CI: 0.96, 1.49 per 5 μg/m(3)], and NO(2) [1.02 (95% CI: 0.98, 1.07 per 10 μg/m(3)], and a statistically significant association with NOx [1.04 (95% CI: 1.00, 1.08) per 20 μg/m(3), p=0.04].CONCLUSIONS: We found suggestive evidence of an association between ambient air pollution and incidence of postmenopausal breast cancer in European women.
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4.
  • Arlien-Soborg, Mai C., et al. (författare)
  • Acromegaly management in the Nordic countries: A Delphi consensus survey
  • 2024
  • Ingår i: CLINICAL ENDOCRINOLOGY. - : WILEY. - 0300-0664 .- 1365-2265.
  • Tidskriftsartikel (refereegranskat)abstract
    • ObjectiveAcromegaly is associated with increased morbidity and mortality if left untreated. The therapeutic options include surgery, medical treatment, and radiotherapy. Several guidelines and recommendations on treatment algorithms and follow-up exist. However, not all recommendations are strictly evidence-based. To evaluate consensus on the treatment and follow-up of patients with acromegaly in the Nordic countries.MethodsA Delphi process was used to map the landscape of acromegaly management in Denmark, Sweden, Norway, Finland, and Iceland. An expert panel developed 37 statements on the treatment and follow-up of patients with acromegaly. Dedicated endocrinologists (n = 47) from the Nordic countries were invited to rate their extent of agreement with the statements, using a Likert-type scale (1-7). Consensus was defined as >= 80% of panelists rating their agreement as >= 5 or <= 3 on the Likert-type scale.ResultsConsensus was reached in 41% (15/37) of the statements. Panelists agreed that pituitary surgery remains first line treatment. There was general agreement to recommend first-generation somatostatin analog (SSA) treatment after failed surgery and to consider repeat surgery. In addition, there was agreement to recommend combination therapy with first-generation SSA and pegvisomant as second- or third-line treatment. In more than 50% of the statements, consensus was not achieved. Considerable disagreement existed regarding pegvisomant monotherapy, and treatment with pasireotide and dopamine agonists.ConclusionThis consensus exploration study on the management of patients with acromegaly in the Nordic countries revealed a relatively large degree of disagreement among experts, which mirrors the complexity of the disease and the shortage of evidence-based data.
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5.
  • Arthur Hvidtfeldt, Ulla, et al. (författare)
  • Long-term exposure to fine particle elemental components and lung cancer incidence in the ELAPSE pooled cohort
  • 2021
  • Ingår i: Environmental Research. - : Elsevier BV. - 0013-9351 .- 1096-0953. ; 193
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: An association between long-term exposure to fine particulate matter (PM2.5) and lung cancer has been established in previous studies. PM2.5 is a complex mixture of chemical components from various sources and little is known about whether certain components contribute specifically to the associated lung cancer risk. The present study builds on recent findings from the Effects of Low-level Air Pollution: A Study in Europe (ELAPSE) collaboration and addresses the potential association between specific elemental components of PM2.5 and lung cancer incidence.Methods: We pooled seven cohorts from across Europe and assigned exposure estimates for eight components of PM2.5 representing non-tail pipe emissions (copper (Cu), iron (Fe), and zinc (Zn)), long-range transport (sulfur (S)), oil burning/industry emissions (nickel (Ni), vanadium (V)), crustal material (silicon (Si)), and biomass burning (potassium (K)) to cohort participants' baseline residential address based on 100 m by 100 m grids from newly developed hybrid models combining air pollution monitoring, land use data, satellite observations, and dispersion model estimates. We applied stratified Cox proportional hazards models, adjusting for potential confounders (age, sex, calendar year, marital status, smoking, body mass index, employment status, and neighborhood-level socio-economic status).Results: The pooled study population comprised 306,550 individuals with 3916 incident lung cancer events during 5,541,672 person-years of follow-up. We observed a positive association between exposure to all eight components and lung cancer incidence, with adjusted HRs of 1.10 (95% CI 1.05, 1.16) per 50 ng/m(3) PM2.5 K, 1.09 (95% CI 1.02, 1.15) per 1 ng/m3 PM2.5 Ni, 1.22 (95% CI 1.11, 1.35) per 200 ng/m(3) PM2.5 S, and 1.07 (95% CI 1.02, 1.12) per 200 ng/m(3) PM2.5 V. Effect estimates were largely unaffected by adjustment for nitrogen dioxide (NO2). After adjustment for PM2.5 mass, effect estimates of K, Ni, S, and V were slightly attenuated, whereas effect estimates of Cu, Si, Fe, and Zn became null or negative.Conclusions: Our results point towards an increased risk of lung cancer in connection with sources of combustion particles from oil and biomass burning and secondary inorganic aerosols rather than non-exhaust traffic emissions. Specific limit values or guidelines targeting these specific PM2.5 components may prove helpful in future lung cancer prevention strategies.
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6.
  • Assimes, Themistocles L., et al. (författare)
  • Lack of Association Between the Trp719Arg Polymorphism in Kinesin-Like Protein-6 and Coronary Artery Disease in 19 Case-Control Studies
  • 2010
  • Ingår i: Journal of the American College of Cardiology. - : Elsevier BV. - 0735-1097. ; 56:19, s. 1552-1563
  • Tidskriftsartikel (refereegranskat)abstract
    • Objectives We sought to replicate the association between the kinesin-like protein 6 (KIF6) Trp719Arg polymorphism (rs20455), and clinical coronary artery disease (CAD). Background Recent prospective studies suggest that carriers of the 719Arg allele in KIF6 are at increased risk of clinical CAD compared with noncarriers. Methods The KIF6 Trp719Arg polymorphism (rs20455) was genotyped in 19 case-control studies of nonfatal CAD either as part of a genome-wide association study or in a formal attempt to replicate the initial positive reports. Results A total of 17,000 cases and 39,369 controls of European descent as well as a modest number of South Asians, African Americans, Hispanics, East Asians, and admixed cases and controls were successfully genotyped. None of the 19 studies demonstrated an increased risk of CAD in carriers of the 719Arg allele compared with noncarriers. Regression analyses and fixed-effects meta-analyses ruled out with high degree of confidence an increase of >= 2% in the risk of CAD among European 719Arg carriers. We also observed no increase in the risk of CAD among 719Arg carriers in the subset of Europeans with early-onset disease (younger than 50 years of age for men and younger than 60 years of age for women) compared with similarly aged controls as well as all non-European subgroups. Conclusions The KIF6 Trp719Arg polymorphism was not associated with the risk of clinical CAD in this large replication study. (J Am Coll Cardiol 2010;56:1552-63) (C) 2010 by the American College of Cardiology Foundation
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7.
  • Bonnesen, Trine Gade, et al. (författare)
  • Liver diseases in Adult Life after Childhood Cancer in Scandinavia (ALiCCS) : A population-based cohort study of 32,839 one-year survivors
  • 2018
  • Ingår i: International Journal of Cancer. - : Wiley. - 0020-7136. ; 142:4, s. 702-708
  • Tidskriftsartikel (refereegranskat)abstract
    • Information on late onset liver complications after childhood cancer is scarce. To ensure an appropriate follow-up of childhood cancer survivors and reducing late liver complications, the need for comprehensive and accurate information is presented. We evaluate the risk of liver diseases in a large childhood cancer survivor cohort. We included all 1-year survivors of childhood cancer treated in the five Nordic countries. A Cox proportional hazards model was used to estimate hospitalisation rate (hazard) ratios (HRs) for each liver outcome according to type of cancer. We used the risk among survivors of central nervous system tumour as internal reference. With a median follow-up time of 10 years, 659 (2%) survivors had been hospitalised at least once for a liver disease. The risk for hospitalisation for any liver disease was high after hepatic tumour (HR = 6.9) and leukaemia (HR = 1.7). The Danish sub-cohort of leukaemia treated with haematopoietic stem cell transplantation had a substantially higher risk for hospitalisation for all liver diseases combined (HR = 3.8). Viral hepatitis accounted for 286 of 659 hospitalisations corresponding to 43% of all survivors hospitalised for liver disease. The 20-year cumulative risk of viral hepatitis was 1.8% for survivors diagnosed with cancer before 1990 but only 0.3% for those diagnosed after 1990. The risk of liver disease was low but significantly increased among survivors of hepatic tumours and leukaemia. Further studies with focus on the different treatment modalities are needed to further strengthen the prevention of treatment-induced late liver complications.
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8.
  • Chen, Jie, et al. (författare)
  • Long-term exposure to ambient air pollution and bladder cancer incidence in a pooled European cohort : the ELAPSE project
  • 2022
  • Ingår i: British Journal of Cancer. - : Springer Science and Business Media LLC. - 0007-0920 .- 1532-1827. ; 126:10, s. 1499-1507
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: The evidence linking ambient air pollution to bladder cancer is limited and mixed.Methods: We assessed the associations of bladder cancer incidence with residential exposure to fine particles (PM2.5), nitrogen dioxide (NO2), black carbon (BC), warm season ozone (O3) and eight PM2.5 elemental components (copper, iron, potassium, nickel, sulfur, silicon, vanadium, and zinc) in a pooled cohort (N = 302,493). Exposures were primarily assessed based on 2010 measurements and back-extrapolated to the baseline years. We applied Cox proportional hazard models adjusting for individual- and area-level potential confounders.Results: During an average of 18.2 years follow-up, 967 bladder cancer cases occurred. We observed a positive though statistically non-significant association between PM2.5 and bladder cancer incidence. Hazard Ratios (HR) were 1.09 (95% confidence interval (CI): 0.93–1.27) per 5 µg/m3 for 2010 exposure and 1.06 (95% CI: 0.99–1.14) for baseline exposure. Effect estimates for NO2, BC and O3 were close to unity. A positive association was observed with PM2.5 zinc (HR 1.08; 95% CI: 1.00–1.16 per 10 ng/m3).Conclusions: We found suggestive evidence of an association between long-term PM2.5 mass exposure and bladder cancer, strengthening the evidence from the few previous studies. The association with zinc in PM2.5 suggests the importance of industrial emissions.
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9.
  • Chen, Jie, et al. (författare)
  • Long-Term Exposure to Source-Specific Fine Particles and Mortality-A Pooled Analysis of 14 European Cohorts within the ELAPSE Project
  • 2022
  • Ingår i: Environmental Science and Technology. - : American Chemical Society (ACS). - 0013-936X .- 1520-5851. ; 56:13, s. 9277-9290
  • Tidskriftsartikel (refereegranskat)abstract
    • We assessed mortality risks associated with sourcespecific fine particles (PM2.5) in a pooled European cohort of 323,782 participants. Cox proportional hazard models were applied to estimate mortality hazard ratios (HRs) for source-specific PM2.5 identified through a source apportionment analysis. Exposure to 2010 annual average concentrations of source-specific PM2.5 components was assessed at baseline residential addresses. The source apportionment resulted in the identification of five sources: traffic, residual oil combustion, soil, biomass and agriculture, and industry. In single-source analysis, all identified sources were significantly positively associated with increased natural mortality risks. In multisource analysis, associations with all sources attenuated but remained statistically significant with traffic, oil, and biomass and agriculture. The highest association per interquartile increase was observed for the traffic component (HR: 1.06; 95% CI: 1.04 and 1.08 per 2.86 mu g/m(3) increase) across five identified sources. On a 1 mu g/m(3) basis, the residual oil-related PM2.5 had the strongest association (HR: 1.13; 95% CI: 1.05 and 1.22), which was substantially higher than that for generic PM2.5 mass, suggesting that past estimates using the generic PM2.5 exposure response function have underestimated the potential clean air health benefits of reducing fossil-fuel combustion. Source-specific associations with cause-specific mortality were in general consistent with findings of natural mortality.
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10.
  • Fanouriakis, Antonis, et al. (författare)
  • EULAR recommendations for the management of systemic lupus erythematosus : 2023 update
  • 2024
  • Ingår i: Annals of the Rheumatic Diseases. - : HighWire Press. - 0003-4967 .- 1468-2060. ; 83:1, s. 15-29
  • Tidskriftsartikel (refereegranskat)abstract
    • OBJECTIVES: To update the EULAR recommendations for the management of systemic lupus erythematosus (SLE) based on emerging new evidence.METHODS: An international Task Force formed the questions for the systematic literature reviews (January 2018-December 2022), followed by formulation and finalisation of the statements after a series of meetings. A predefined voting process was applied to each overarching principle and recommendation. Levels of evidence and strengths of recommendation were assigned, and participants finally provided their level of agreement with each item.RESULTS: The Task Force agreed on 5 overarching principles and 13 recommendations, concerning the use of hydroxychloroquine (HCQ), glucocorticoids (GC), immunosuppressive drugs (ISDs) (including methotrexate, mycophenolate, azathioprine, cyclophosphamide (CYC)), calcineurin inhibitors (CNIs, cyclosporine, tacrolimus, voclosporin) and biologics (belimumab, anifrolumab, rituximab). Advice is also provided on treatment strategies and targets of therapy, assessment of response, combination and sequential therapies, and tapering of therapy. HCQ is recommended for all patients with lupus at a target dose 5 mg/kg real body weight/day, considering the individual's risk for flares and retinal toxicity. GC are used as 'bridging therapy' during periods of disease activity; for maintenance treatment, they should be minimised to equal or less than 5 mg/day (prednisone equivalent) and, when possible, withdrawn. Prompt initiation of ISDs (methotrexate, azathioprine, mycophenolate) and/or biological agents (anifrolumab, belimumab) should be considered to control the disease and facilitate GC tapering/discontinuation. CYC and rituximab should be considered in organ-threatening and refractory disease, respectively. For active lupus nephritis, GC, mycophenolate or low-dose intravenous CYC are recommended as anchor drugs, and add-on therapy with belimumab or CNIs (voclosporin or tacrolimus) should be considered. Updated specific recommendations are also provided for cutaneous, neuropsychiatric and haematological disease, SLE-associated antiphospholipid syndrome, kidney protection, as well as preventative measures for infections, osteoporosis, cardiovascular disease.CONCLUSION: The updated recommendations provide consensus guidance on the management of SLE, combining evidence and expert opinion.
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11.
  • Frederiksen, Line Elmerdahl, et al. (författare)
  • Psychiatric disorders in childhood cancer survivors in Denmark, Finland, and Sweden : a register-based cohort study from the SALiCCS research programme
  • 2022
  • Ingår i: The Lancet Psychiatry. - 2215-0366 .- 2215-0374. ; 69
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: A childhood cancer diagnosis and treatment-induced somatic late effects can affect the long-term mental health of survivors. We aimed to explore whether childhood cancer survivors are at higher risk of psychiatric disorders later in life than their siblings and the general population. Methods: In this register-based cohort study (part of the Socioeconomic Consequences in Adult Life after Childhood Cancer [SALiCCS] research programme), we included 5-year survivors of childhood cancer diagnosed before 20 years of age between Jan 1, 1974 and Dec 31, 2011, in Denmark, Finland, and Sweden. In Denmark and Sweden, 94·7% of individuals were born in a Nordic country (ie, Denmark, Finland, Iceland, Norway, or Sweden); similar information was not available in Finland. Data on ethnicity were not collected. Survivors were compared with their siblings and randomly selected individuals from the general population who were matched to the survivors by year of birth, sex, and geographical region. We followed up our study population from 5 years after the childhood cancer diagnosis or corresponding calendar date for matched individuals (the index date) until Aug 11, 2017, and assessed information on hospital contacts for any and specific psychiatric disorders. For siblings, the index date was defined as 5 years from the date on which they were of the same age as their sibling survivor when diagnosed with cancer. Findings: The study population included 18 621 childhood cancer survivors (9934 [53·3%] males and 8687 [46·7%] females), 24 775 siblings (12 594 [50·8%] males and 12 181 [49·2%] females), and 88 630 matched individuals (47 300 [53·4%] males and 41 330 [46·6%] females). The cumulative incidence proportion of having had a psychiatric hospital contact by 30 years of age between Jan 1, 1979, and Aug 11, 2017, was 15·9% (95% CI 15·3–16·5) for childhood cancer survivors, 14·0% (13·5–14·5) for siblings, and 12·7% (12·4–12·9) for matched individuals. Despite a small absolute difference, survivors were at higher relative risk of any psychiatric hospital contact than their siblings (1·39, 1·31–1·48) and matched individuals (hazard ratio 1·34, 95% CI 1·28–1·39). The higher risk persisted at the age of 50 years. Survivors had a higher burden of recurrent psychiatric hospital contacts and had more hospital contacts for different psychiatric disorders than their siblings and the matched individuals. Interpretation: Childhood cancer survivors are at higher long-term risk of psychiatric disorders than their siblings and matched individuals from the general population. To improve mental health and the overall quality of life after childhood cancer, survivorship care should include a focus on early signs of mental health problems, especially among high-risk groups of survivors. Funding: NordForsk, Aarhus University, Swedish Childhood Cancer Foundation, Danish Health Foundation, and Swiss National Science Foundation.
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12.
  • Hanssen, Kine Œ, et al. (författare)
  • The Bromotyrosine derivative Ianthelline isolated from the arctic marine sponge Stryphnus fortis inhibits marine micro- and macrobiofouling
  • 2014
  • Ingår i: Marine Biotechnology. - : Springer Science and Business Media LLC. - 1436-2228 .- 1436-2236. ; 16:6, s. 684-694
  • Tidskriftsartikel (refereegranskat)abstract
    • The inhibition of marine biofouling by the bromotyrosine derivative ianthelline, isolated from the Arctic marine sponge Stryphnus fortis, is described. All major stages of the fouling process are investigated. The effect of ianthelline on adhesion and growth of marine bacteria and microalgae is tested to investigate its influence on the initial microfouling process comparing with the known marine antifoulant barettin as a reference. Macrofouling is studied via barnacle (Balanus improvisus) settlement assays and blue mussel (Mytilus edulis) phenoloxidase inhibition. Ianthelline is shown to inhibit both marine micro- and macrofoulers with a pronounced effect on marine bacteria (minimum inhibitory concentration (MIC) values 0.1–10 μg/mL) and barnacle larval settlement (IC50=3.0 μg/mL). Moderate effects are recorded on M. edulis (IC50=45.2 μg/mL) and microalgae, where growth is more affected than surface adhesion. The effect of ianthelline is also investigated against human pathogenic bacteria. Ianthelline displayed low micromolar MIC values against several bacterial strains, both Gram positive and Gram negative, down to 2.5 μg/mL. In summary, the effect of ianthelline on 20 different representative marine antifouling organisms and seven human pathogenic bacterial strains is presented.
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13.
  • Haugaard-Kedström, Linda M., et al. (författare)
  • A High-Affinity Peptide Ligand Targeting Syntenin Inhibits Glioblastoma
  • 2021
  • Ingår i: Journal of Medicinal Chemistry. - : American Chemical Society (ACS). - 0022-2623 .- 1520-4804. ; 64:3, s. 1423-1434
  • Tidskriftsartikel (refereegranskat)abstract
    • Despite the recent advances in cancer therapeutics, highly aggressive cancer forms, such as glioblastoma (GBM), still have very low survival rates. The intracellular scaffold protein syntenin, comprising two postsynaptic density protein-95/discslarge/zona occludens-1 (PDZ) domains, has emerged as a novel therapeutic target in highly malignant phenotypes including GBM. Here, we report the development of a novel, highly potent, and metabolically stable peptide inhibitor of syntenin, KSL-128114, which binds the PDZ1 domain of syntenin with nanomolar affinity. KSL-128114 is resistant toward degradation in human plasma and mouse hepatic microsomes and displays a global PDZ domain selectivity for syntenin. An X-ray crystal structure reveals that KSL128114 interacts with syntenin PDZ1 in an extended noncanonical binding mode. Treatment with KSL-128114 shows an inhibitory effect on primary GBM cell viability and significantly extends survival time in a patient-derived xenograft mouse model. Thus, KSL-128114 is a novel promising candidate with therapeutic potential for highly aggressive tumors, such as GBM.
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14.
  • Hvidtfeldt, Ulla Arthur, et al. (författare)
  • Long term exposure to air pollution and kidney parenchyma cancer – Effects of low-level air pollution : a Study in Europe (ELAPSE)
  • 2022
  • Ingår i: Environmental Research. - : Academic Press Inc.. - 0013-9351 .- 1096-0953. ; 215
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Particulate matter (PM) is classified as a group 1 human carcinogen. Previous experimental studies suggest that particles in diesel exhaust induce oxidative stress, inflammation and DNA damage in kidney cells, but the evidence from population studies linking air pollution to kidney cancer is limited.METHODS: We pooled six European cohorts (N = 302,493) to assess the association of residential exposure to fine particles (PM2.5), nitrogen dioxide (NO2), black carbon (BC), warm season ozone (O3) and eight elemental components of PM2.5 (copper, iron, potassium, nickel, sulfur, silicon, vanadium, and zinc) with cancer of the kidney parenchyma. The main exposure model was developed for year 2010. We defined kidney parenchyma cancer according to the International Classification of Diseases 9th and 10th Revision codes 189.0 and C64. We applied Cox proportional hazards models adjusting for potential confounders at the individual and area-level.RESULTS: The participants were followed from baseline (1985–2005) to 2011–2015. A total of 847 cases occurred during 5,497,514 person-years of follow-up (average 18.2 years). Median (5–95%) exposure levels of NO2, PM2.5, BC and O3 were 24.1 μg/m3 (12.8–39.2), 15.3 μg/m3 (8.6–19.2), 1.6 10−5 m−1 (0.7–2.1), and 87.0 μg/m3 (70.3–97.4), respectively. The results of the fully adjusted linear analyses showed a hazard ratio (HR) of 1.03 (95% confidence interval [CI]: 0.92, 1.15) per 10 μg/m³ NO2, 1.04 (95% CI: 0.88, 1.21) per 5 μg/m³ PM2.5, 0.99 (95% CI: 0.89, 1.11) per 0.5 10−5 m−1 BCE, and 0.88 (95% CI: 0.76, 1.02) per 10 μg/m³ O3. We did not find associations between any of the elemental components of PM2.5 and cancer of the kidney parenchyma.CONCLUSION: We did not observe an association between long-term ambient air pollution exposure and incidence of kidney parenchyma cancer.
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15.
  • Hvidtfeldt, Ulla Arthur, et al. (författare)
  • Long-term low-level ambient air pollution exposure and risk of lung cancer - A pooled analysis of 7 European cohorts
  • 2021
  • Ingår i: Environment International. - : Elsevier BV. - 0160-4120 .- 1873-6750. ; 146
  • Tidskriftsartikel (refereegranskat)abstract
    • Background/aim: Ambient air pollution has been associated with lung cancer, but the shape of the exposure-response function - especially at low exposure levels - is not well described. The aim of this study was to address the relationship between long-term low-level air pollution exposure and lung cancer incidence.Methods: The Effects of Low-level Air Pollution: a Study in Europe (ELAPSE) collaboration pools seven cohorts from across Europe. We developed hybrid models combining air pollution monitoring, land use data, satellite observations, and dispersion model estimates for nitrogen dioxide (NO2), fine particulate matter (PM2.5), black carbon (BC), and ozone (O-3) to assign exposure to cohort participants' residential addresses in 100 m by 100 m grids. We applied stratified Cox proportional hazards models, adjusting for potential confounders (age, sex, calendar year, marital status, smoking, body mass index, employment status, and neighborhood-level socioeconomic status). We fitted linear models, linear models in subsets, Shape-Constrained Health Impact Functions (SCHIF), and natural cubic spline models to assess the shape of the association between air pollution and lung cancer at concentrations below existing standards and guidelines.Results: The analyses included 307,550 cohort participants. During a mean follow-up of 18.1 years, 3956 incident lung cancer cases occurred. Median (Q1, Q3) annual (2010) exposure levels of NO2, PM2.5, BC and O-3 (warm season) were 24.2 mu g/m(3) (19.5, 29.7), 15.4 mu g/m(3) (12.8, 17.3), 1.6 10(-5)m(-1) (1.3, 1.8), and 86.6 mu g/m(3) (78.5, 92.9), respectively. We observed a higher risk for lung cancer with higher exposure to PM2.5 (HR: 1.13, 95% CI: 1.05, 1.23 per 5 mu g/m(3)). This association was robust to adjustment for other pollutants. The SCHIF, spline and subset analyses suggested a linear or supra-linear association with no evidence of a threshold. In subset analyses, risk estimates were clearly elevated for the subset of subjects with exposure below the EU limit value of 25 mu g/m(3). We did not observe associations between NO2, BC or O-3 and lung cancer incidence.Conclusions: Long-term ambient PM2.5 exposure is associated with lung cancer incidence even at concentrations below current EU limit values and possibly WHO Air Quality Guidelines.
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16.
  • Kallemose, Thomas, et al. (författare)
  • Political trust in the handling of the COVID-19 pandemic: a survey in Denmark and Sweden
  • 2023
  • Ingår i: BMC Global and Public Health. - : BioMed Central (BMC). - 2731-913X. ; 1:12
  • Tidskriftsartikel (refereegranskat)abstract
    • BackgroundThe initial responses to the COVID-19 pandemic in Denmark and Sweden differed markedly. Balancing disparate concerns was crucial to generate trust in the COVID-19 restrictions. The aim was to investigate the extent to which there was trust in the handling of the pandemic by the Danish and Swedish governments and public health authorities in each country. A further aim was also to investigate the characteristics of those in Denmark and Sweden who expressed the lowest degree of trust.MethodsCross-sectional surveys were conducted in 2021, using web panels that are nationally representative of the socio-demographic characteristics. The population consisted of 2619 individuals from Denmark and 2633 from Sweden, representative of the age, sex and region of residence of the populations aged ≥ 18 years. Trust in government and health authorities was captured in two separate trust questions on a 5-point Likert scale and dichotomized into low trusters and non-low trusters for analysis.ResultsApproximately, 61% of the Danish respondents expressed moderately large or very large trust in the government’s handling of the pandemic. The corresponding proportion for Sweden was 42%. The proportion of low trusters was 11% in Denmark and 34% in Sweden (p < 0.001). Moderately large or very large trust in the public health authority’s handling was expressed by 83% of the Danish respondents and 74% of the Swedish respondents. The proportion of low trusters was 5% in Denmark and 17% in Sweden (p < 0.001). In both countries, trust was lower among men than among women. Age and education were associated with trust but differed between countries (p <  = 0.011).ConclusionsIn this study, differences in trust between Denmark and Sweden and both overall and within socio-demographic factors were observed. However, given the limitations and bias in the study, it is difficult to determine the cause and true size of these differences. With that in mind, we still believe specific populations and subgroups within those populations have the potential to affect trust in handling of the COVID-19 pandemic, and that these should be kept in mind when developing and communicating responses to pandemics.
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17.
  • Kirk, Jeanette, et al. (författare)
  • Challenges in co-designing an intervention to increase mobility in older patients : a qualitative study
  • 2021
  • Ingår i: Journal of Health Organization & Management. - : Emerald Group Publishing Limited. - 1477-7266 .- 1758-7247. ; 35:9, s. 140-162
  • Tidskriftsartikel (refereegranskat)abstract
    • Purpose The aim of this study is to explore and discuss key challenges associated with having stakeholders take part in co-designing a health care intervention to increase mobility in older medical patients admitted to two medical departments at two hospitals in Denmark. Design/methodology/approach The study used a qualitative design to investigate the challenges of co-designing an intervention in five workshops involving health professionals, patients and relatives. "Challenges" are understood as "situations of being faced with something that needs great mental or physical effort in order to be done successfully and therefore tests a persons ability" (Cambridge Dictionary). Thematic content analysis was conducted with a background in the analytical question: "What key challenges arise in the material in relation to the co-design process?". Findings Two key challenges were identified: engagement and facilitation. These consisted of five sub-themes: recruiting patients and relatives, involving physicians, adjusting to a new researcher role, utilizing contextual knowledge and handling ethical dilemmas. Research limitations/implications The population of patients and relatives participating in the workshops was small, which likely affected the co-design process. Practical implications Researchers who want to use co-design must be prepared for the extra time required and the need for skills concerning engagement, communication, facilitation, negotiation and resolution of conflict. Time is also required for ethical discussions and considerations concerning different types of knowledge creation. Originality/value Engaging stakeholders in co-design processes is increasingly encouraged. This study documents the key challenges in such processes and reports practical implications.
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18.
  • Kirk, Jeanette Wassar, et al. (författare)
  • A tailored strategy for designing the Walk-Copenhagen (WALK-Cph) intervention to increase mobility in hospitalised older medical patients: a protocol for the qualitative part of the WALK-Cph project
  • 2018
  • Ingår i: BMJ Open. - : BMJ PUBLISHING GROUP. - 2044-6055. ; 8:3
  • Tidskriftsartikel (refereegranskat)abstract
    • Introduction Older medical patients (amp;gt;65 years) represent 54% of the admissions to Danish medical and emergency departments. Acute admissions and bed rest during hospitalisation are independent risk factors for death and dependency in older patients. Even short hospitalisations are associated with increased dependency in activities of daily living after discharge. Interventions that increase mobility during hospitalisation are therefore important. The purpose of this protocol is to describe the intervention design of the WALK =-Copenhagen project, aimed at increasing 24 hours mobility in older medical patients during acute hospitalisations and following discharge. Methods and analysis This study is based on ethnographic fieldwork and interviews. Workshops are used to develop and co-design the intervention in collaboration with key stakeholders (patients, relatives, health professionals and researchers). The theory of cultural learning processes, and fire cultural historical activity theory will be used to help us understand the interaction between health professionals, structures arid objects in relation to mobility in the medical departments. Ethics and dissemination The project will adhere to the directives of the Helsinki Declaration. Ethical approval was not required for the study since formal ethical approval is not mandatory for studies that do not involve biomedical issues (I-Suite no: 05078) according to Danish law. Informed consent was obtained for all participants. The results will be disseminated to health professionals, managers, patients arid relatives, who will be invited to afternoon meetings where the project will be discussed. The results will be published in peer-reviewed scientific journals and presented at scientific conferences.
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19.
  • Kirk, Jeanette Wassar, et al. (författare)
  • Adaptations and modifications to a co-designed intervention and its clinical implementation : a qualitative study in Denmark
  • 2021
  • Ingår i: BMC Health Services Research. - : BMC. - 1472-6963. ; 21:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Background There is a long-standing debate in implementation research on whether adaptations to evidence-based interventions (EBIs) are desirable in health care. If an intervention is adapted and not delivered as conceived and planned, it is said to have low fidelity. The WALK-Cph project was developed based on the assumption that involving stakeholders in co-design processes would facilitate the fidelity of an intervention to increase the mobility of acutely admitted older medical patients and its implementation in two hospitals in Denmark. The purpose of this study is to describe and analyse adaptations and modifications that were made to the co-designed WALK-Cph intervention and its implementation. Methods This study used a qualitative design. An ethnographic field study was performed using participant observations, workshops and semi-structured interviews. Data were analysed twice using the Framework Method. The first analysis was based on the frameworks from Stirman, Moore and Proctor. The second analysis, a retrospective modifications analysis, was based on the Adaptation-Impact Framework. Results Many different types of adaptations and modifications were made to the WALK-Cph intervention and its implementation plan. Most of the modifications were made on the contents of the intervention. In total, 44 adaptations and modifications were made, of which 21 were planned (adaptations) and 23 were made haphazardly (modifications). Most of the content and context adaptations and modifications made on the intervention had a mixed result regarding enhanced fidelity. The retrospective modifications analysis showed that modifications were ongoing and both situationally and contextually shaped. Conclusions Although an extensive co-design process was carried out to facilitate the fidelity of the WALK-Cph intervention, this study showed that many adaptations and modifications were still made to both the intervention and its implementation plan. It could indicate that the co-design process had a small effect or that adaptations and modifications are ongoing and both situationally and contextually shaped, which challenge the assumption and the desire to be able to plan and control changes.
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20.
  • Kirk, Jeanette Wassar, et al. (författare)
  • Co-designing implementation strategies for the WALK-Cph intervention in Denmark aimed at increasing mobility in acutely hospitalized older patients : a qualitative analysis of selected strategies and their justifications
  • 2022
  • Ingår i: BMC Health Services Research. - : BMC. - 1472-6963. ; 22:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Selecting appropriate strategies to target barriers to implementing interventions represents a considerable challenge in implementation research and practice. The aim was to investigate what categories of implementation strategies were selected by health care practitioners and their managers in a co-design process and how they justified these strategies aimed at facilitating the implementation of the WALK-Cph intervention. Methods: The study used a qualitative research design to explore what implementation strategies were selected and the justifications for selecting these strategies. Workshops were used because this qualitative method is particularly well suited for studying co-design processes that involve substantial attention to social interaction and the context. Data were 1) analyzed deductively based on the Proctor et al. taxonomy of implementation strategies, 2) categorized in accordance with the ERIC compilation of implementation strategies by Powell et al., and 3) analyzed to examine the justification for the selected strategies by the Proctor et al. framework for justifications of implementation strategies. Results: Thirteen different types of implementation strategies were chosen across two hospitals. The deductive analysis showed that selection of implementation strategies was based on pragmatic and theoretical justifications. The contents of the two types of justifications were thematized into nine subthemes. Conclusion: This study contributes with knowledge about categories and justification of implementation strategies selected in a co-design process. In this study, implementation strategies were selected through pragmatic and theoretical justifications. This points to a challenge in balancing strategies based on practice-based and research-based knowledge and thereby selection of strategies with or without proven effectiveness.
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21.
  • Kirk, Jeanette Wassar, et al. (författare)
  • How do oilcloth sessions work? A realist evaluation approach to exploring ripple effects in an implementation strategy
  • 2024
  • Ingår i: Journal of Health Organization & Management. - : EMERALD GROUP PUBLISHING LTD. - 1477-7266 .- 1758-7247. ; 38:9, s. 195-215
  • Tidskriftsartikel (refereegranskat)abstract
    • PurposeTo explore the mechanisms of the implementation strategy, "oilcloth sessions" and understand and explain the ripple effects of oilcloth sessions as a strategy to implement a new emergency department.Design/methodology/approachA qualitative design was used whereby data were collected using field notes from an ethnographic study of the oilcloth sessions and follow-up semi-structured interviews with staff, managers and key employees who participated in the oilcloth sessions. The data analysis was inspired by the realist evaluation approach of generative causality proposed by Pawson and Tilley.FindingsThe primary ripple effect was that the oilcloth sessions were used for different purposes than the proposed program theory, including being used as: (1) a stage, (2) a battlefield, (3) a space for imagination and (4) a strategic management tool influencing the implementation outcomes. The results bring essential knowledge that may help to explain why and how a well-defined implementation strategy has unplanned outcomes.Originality/valueUnintended outcomes of implementation strategies are an underexplored issue. This study may help implementation researchers rethink the activities required to reduce unintended negative outcomes or explore potential unplanned outcomes and, in this way, hinder or enhance outcomes, effectiveness and sustainability. Future studies within implementation research should incorporate attention to unintended outcomes to fully understand the impact of implementation strategies.
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22.
  • Kirk, Jeanette Wassar, et al. (författare)
  • Influences of specialty identity when implementing a new emergency department in Denmark : a qualitative study
  • 2024
  • Ingår i: BMC Health Services Research. - London : BioMed Central (BMC). - 1472-6963. ; 24:1, s. 1-13
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: The Danish Health Authority recommended the implementation of new types of emergency departments. Organizational changes in the hospital sector challenged the role, identity, and autonomy of medical specialists. They tend to identify with their specialty, which can challenge successful implementation of change. However, investigations on specialty identity are rare in implementation science, and how the co-existence of different specialty identities influences the implementation of new emergency departments needs to be explored for the development of tailored implementation strategies. The aim of this study was to examine how medical specialty identity influences collaboration between physicians when implementing a new emergency department in Denmark. Methods: Qualitative methods in the form of participants’ observations at 13 oilcloth sessions (a micro-simulation method) were conducted followed up by 53 individual semi-structured interviews with participants from the oilcloth sessions. Out of the 53 interviews, 26 were conducted with specialists. Data from their interviews are included in this study. Data were analysed deductively inspired by Social Identity Theory. Results: The analysis yielded three overarching themes: [1] ongoing creation and re-creation of specialty identity through boundary drawing; [2] social categorization and power relations; and [3] the patient as a boundary object. Conclusions: Specialty identity is an important determinant of collaboration among physicians when implementing a new emergency department. Specialty identity involves social categorization, which entails ongoing creation and re-creation of boundary drawing and exercising of power among the physicians. In some situations, the patient became a positive boundary object, increasing the possibility for a successful collaboration and supporting successful implementation, but direct expressions of boundaries and mistrust were evident. Both were manifested through a dominating power expressed through social categorization in the form of in- and out-groups and in an “us and them” discourse, which created distance and separation among physicians from different specialties. This distancing and separation became a barrier to the implementation of the new emergency department. © 2024, The Author(s).
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23.
  • Kirk, Jeanette Wassar, et al. (författare)
  • Oilcloth sessions as an implementation strategy : a qualitative study in Denmark
  • 2022
  • Ingår i: BMC Medical Education. - : BMC. - 1472-6920. ; 22:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Background The aim of this study was to explore healthcare professionals, managers, and other key employees experiences of oilcloth sessions as a strategy when implementing new emergency departments in Denmark, based on their participations in these sessions. The study addresses the importance of securing alignment in implementation strategies. Too often, this does not get enough attention in the literature and in practice. In this study, alignment among components was achieved in an educational implementation strategy called oilcloth sessions. Methods The study is based on participants observations of 13 oilcloth sessions and follow-up via 53 semi-structured interviews with the board of directors, managers, and key employees from the present emergency department and different specialty departments. Data were analysed deductively using Biggs and Tangs model of didactic alignment. Results The analysis showed the complexity of challenges when using oilcloth sessions as a strategy when implementing a new emergency department described in terms of three phases and nine main themes (a-i): the preparation phase: (a) preparing individually and collectively, (b) objectives, (c) involving participants, (d) selecting cases; the execution phase: (e) using materials, (f) facilitating the sessions, (g) temporal structures; evaluation: (h) following up on the sessions, (i) adapting to the context. Conclusions This study shows that it is important to ensure alignment among elements in implementation strategies. Thus, oilcloth sessions with high alignment are useful if the challenges experienced are to be overcome and the strategy will be experienced as a useful way to support the implementation of a new emergency department from the participants point of view. Bigg and Tangs didactic model is useful as an analytical framework to ensure alignment in implementation strategies in general.
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24.
  • Labriere, Christophe, et al. (författare)
  • Heterocyclic cellular lipid peroxidation inhibitors inspired by the marine antioxidant barettin
  • 2019
  • Ingår i: Bioorganic chemistry (Print). - : Elsevier BV. - 0045-2068. ; 84, s. 106-114
  • Tidskriftsartikel (refereegranskat)abstract
    • The marine environment remains a rich source for the discovery and development of novel bioactive compounds. The present paper describes the design, synthesis and biological evaluation of a library of small molecule heterocyclic mimetics of the marine 2,5-diketopiperazine barettin which is a powerful natural antioxidant. By mainly focusing on the influence from the brominated indole and heterocyclic core of barettin, a library of 19 compounds was prepared. The compounds comprised a heterocyclic core, either a 2,5 diketopiperazine, an imidazolidinedione or a thioxothiazolidinone, which were mainly monosubstituted with ranging bulky substituents. The prepared compounds were screened for activity in a cellular lipid peroxidation assay using HepG2 cells. Several of the synthetic compounds showed antioxidant properties superior to the positive control barettin. Two of the prepared compounds displayed inhibitory activity similar to commercial antioxidants with significant inhibition at low µg/mL concentrations. The toxicity of the compounds was also investigated against MRC-5 lung fibroblasts and none of the included compounds displayed any toxicity at 50 µg/mL.
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25.
  • Licht, Sofie de Fine, et al. (författare)
  • Temporal changes in the probability of live birth among female survivors of childhood cancer : A population-based Adult Life After Childhood Cancer in Scandinavia (ALiCCS) study in five nordic countries
  • 2021
  • Ingår i: Cancer. - : Wiley. - 0008-543X .- 1097-0142. ; 127:20, s. 3881-3892
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: During the past 4 decades, there has been a growing focus on preserving the fertility of patients with childhood cancer; however, no large studies have been conducted of live births across treatment decades during this period. Therefore, the authors estimated the potential birth deficit in female childhood cancer survivors and the probability of live births. METHODS: In total, 8886 women were identified in the 5 Nordic cancer registries in whom a childhood cancer had been diagnosed during 1954 through 2006. A population comparison cohort of 62,903 women was randomly selected from the central population registries matched by age and country. All women were followed for live births recorded in medical birth registries. The cumulative probability and the risk ratio (RR) with 95% confidence intervals (CIs) of a live birth were calculated by maternal age across treatment decades. RESULTS: The probability of a live birth increased with treatment decade, and, at age 30 years, the rate for survivors most recently diagnosed was close to the rate among the general population (1954-1969: RR, 0.65 [95% CI, 0.54-0.78]; 1970s: RR, 0.67 [95% CI, 0.60-0.74]; 1980s: RR, 0.69 [95% CI, 0.64-0.74]; 1990s: RR, 0.91 [95% CI, 0.87-0.95]; 2000s: RR, 0.94 [95% CI, 0.91-0.97]). CONCLUSIONS: Female childhood cancer survivors had a lower probability of a live birth than women in the general population, although, in survivors diagnosed after 1989, the probability was close to that of the general population. Because the pattern of live births differs by cancer type, continuous efforts must be made to preserve fertility, counsel survivors, and refer them rapidly to fertility treatment if necessary. LAY SUMMARY: The purpose of this study was to compare the probability of giving birth to a liveborn child in female survivors of childhood cancer with that of women in the general population. Survivors of childhood cancer had a lower probability of live births than women in the general population, although survivors diagnosed after 1989 had a probability close to that of the general population. Continuing focus on how to preserve the potential for fertility among female patients with childhood cancer during treatment is important to increase their chances of having a child.
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26.
  • Liu, Shuo, et al. (författare)
  • Long-term exposure to low-level air pollution and incidence of asthma : the ELAPSE project
  • 2021
  • Ingår i: European Respiratory Journal. - : European Respiratory Society (ERS). - 0903-1936 .- 1399-3003. ; 57:6
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Long-term exposure to ambient air pollution has been linked to childhood-onset asthma, although evidence is still insufficient. Within the multicentre project Effects of Low-Level Air Pollution: A Study in Europe (ELAPSE), we examined the associations of long-term exposures to particulate matter with a diameter <2.5 mu m (PM2.5), nitrogen dioxide (NO2) and black carbon (BC) with asthma incidence in adults.Methods: We pooled data from three cohorts in Denmark and Sweden with information on asthma hospital diagnoses. The average concentrations of air pollutants in 2010 were modelled by hybrid land-use regression models at participants' baseline residential addresses. Associations of air pollution exposures with asthma incidence were explored with Cox proportional hazard models, adjusting for potential confounders.Results: Of 98326 participants, 1965 developed asthma during a mean follow-up of 16.6 years. We observed associations in fully adjusted models with hazard ratios of 1.22 (95% CI 1.04-1.43) per 5 mu g.m(-3) for PM2.5, 1.17 (95% CI 1.10-1.25) per 10 mu g.m(-3) for NO2 and 1.15 (95% CI 1.08-1.23) per 0.5 x 10(-5) m(-1) for BC. Hazard ratios were larger in cohort subsets with exposure levels below the European Union and US limit values and possibly World Health Organization guidelines for PM2.5 and NO2. NO 2 and BC estimates remained unchanged in two-pollutant models with PM2.5, whereas PM2.5 estimates were attenuated to unity. The concentration-response curves showed no evidence of a threshold.Conclusions: Long-term exposure to air pollution, especially from fossil fuel combustion sources such as motorised traffic, was associated with adult-onset asthma, even at levels below the current limit values.
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27.
  • Liu, Shuo, et al. (författare)
  • Long-term exposure to low-level air pollution and incidence of chronic obstructive pulmonary disease : The ELAPSE project
  • 2021
  • Ingår i: Environment International. - : Elsevier BV. - 0160-4120 .- 1873-6750. ; 146
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Air pollution has been suggested as a risk factor for chronic obstructive pulmonary disease (COPD), but evidence is sparse and inconsistent.Objectives: We examined the association between long-term exposure to low-level air pollution and COPD incidence.Methods: Within the 'Effects of Low-Level Air Pollution: A Study in Europe' (ELAPSE) study, we pooled data from three cohorts, from Denmark and Sweden, with information on COPD hospital discharge diagnoses. Hybrid land use regression models were used to estimate annual mean concentrations of particulate matter with a diameter < 2.5 mu m (PM2.5), nitrogen dioxide (NO2), and black carbon (BC) in 2010 at participants' baseline residential addresses, which were analysed in relation to COPD incidence using Cox proportional hazards models.Results: Of 98,058 participants, 4,928 developed COPD during 16.6 years mean follow-up. The adjusted hazard ratios (HRs) and 95% confidence intervals for associations with COPD incidence were 1.17 (1.06, 1.29) per 5 mu g/m(3) for PM2.5, 1.11 (1.06, 1.16) per 10 mu g/m(3) for NO2, and 1.11 (1.06, 1.15) per 0.5 10(-5) m(-1) for BC. Associations persisted in subset participants with PM2.5 or NO2 levels below current EU and US limit values and WHO guidelines, with no evidence for a threshold. HRs for NO2 and BC remained unchanged in two-pollutant models with PM2.5, whereas the HR for PM2.5 was attenuated to unity with NO2 or BC.Conclusions: Long-term exposure to low-level air pollution is associated with the development of COPD, even below current EU and US limit values and possibly WHO guidelines. Traffic-related pollutants NO2 and BC may be the most relevant.
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28.
  • Moodie, Lindon W. K., et al. (författare)
  • Synthetic analogs of stryphnusin isolated from the marine sponge : Stryphnus fortis inhibit acetylcholinesterase with no effect on muscle function or neuromuscular transmission
  • 2016
  • Ingår i: Organic and biomolecular chemistry. - : Royal Society of Chemistry (RSC). - 1477-0520 .- 1477-0539. ; 14:47, s. 11220-11229
  • Tidskriftsartikel (refereegranskat)abstract
    • The marine secondary metabolite stryphnusin (1) was isolated from the boreal sponge Stryphnus fortis, collected off the Norwegian coast. Given its resemblance to other natural acetylcholinesterase antagonists, it was evaluated against electric eel acetylcholinesterase and displayed inhibitory activity. A library of twelve synthetic phenethylamine analogs, 2a-7a and 2b-7b, containing tertiary and quaternary amines respectively were synthesized to investigate the individual structural contributions to the activity. Compound 7b was the strongest competitive inhibitor of both acetylcholinesterase and butyrylcholinesterase with IC50 values of 57 and 20 μM, respectively. This inhibitory activity is one order of magnitude higher than the positive control physostigmine, and is comparable with several other marine acetylcholinesterase inhibitors. The physiological effect of compound 7b on muscle function and neuromuscular transmission was studied and revealed a selective mode of action at the investigated concentration. This data is of importance as the interference of therapeutic acetylcholinesterase inhibitors with neuromuscular transmission can be problematic and lead to unwanted side effects. The current findings also provide additional insights into the structure-activity relationship of both natural and synthetic acetylcholinesterase inhibitors.
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29.
  • Nilsen, Per, et al. (författare)
  • Acceptability of restrictions in the COVID-19 pandemic: a population-based survey in Denmark and Sweden
  • 2023
  • Ingår i: Frontiers in Public Health. - : FRONTIERS MEDIA SA. - 2296-2565. ; 11
  • Tidskriftsartikel (refereegranskat)abstract
    • IntroductionDenmark and Sweden initially adopted different responses to the COVID-19 pandemic although the two countries share many characteristics. Denmark responded swiftly with many mandatory restrictions. In contrast, Sweden relied on voluntary restrictions and a more "relaxed" response during the first wave of the pandemic. However, increased rates of COVID-19 cases led to a new approach that involved many more mandatory restrictions, thus making Swedens response similar to Denmarks in the second wave of the pandemic. AimThe aim was to investigate and compare the extent to which the populations in Denmark and Sweden considered the COVID-19 restrictions to be acceptable during the first two waves of the pandemic. The study also aimed to identify the characteristics of those who were least accepting of the restrictions in the two countries. Materials and methodsCross-sectional surveys were conducted in Denmark and Sweden in 2021. The study population was sampled from nationally representative web panels in the two countries, consisting of 2,619 individuals from Denmark and 2,633 from Sweden. The questionnaire captured key socio-demographic characteristics. Acceptability was operationalized based on a theoretical framework consisting of seven constructs and one overarching construct. ResultsThe respondents age and gender patterns were similar in the two countries. The proportion of respondents in Denmark who agreed with the statements ("agree" alternative) that captured various acceptability constructs was generally higher for the first wave than the second wave of the pandemic. The opposite pattern was seen for Sweden. In Denmark, 66% in the first wave and 50% in the second wave were accepting of the restrictions. The corresponding figures for Sweden was 42% (first wave) and 47% (second wave). Low acceptance of the restrictions, defined as the 25% with the lowest total score on the seven acceptability statements, was associated with younger age, male gender and lower education levels. ConclusionRespondents in Sweden were more accepting of the restrictions in the second wave, when the country used many mandatory restrictions. In contrast, respondents in Denmark were more accepting of the restrictions in the first wave than in the second wave, implying an increased weariness to comply with the restrictions over time. There were considerable socio-demographic differences between those who expressed low acceptance of the restrictions and the others in both countries, suggesting the importance of tailoring communication about the pandemic to different segments of the population.
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30.
  • Nilsen, Per, 1960-, et al. (författare)
  • Implementing social distancing policy measures in the battle against the coronavirus : protocol of a comparative study of Denmark and Sweden
  • 2020
  • Ingår i: Implementation Science Communications. - : Springer Nature. - 2662-2211. ; 1:77
  • Tidskriftsartikel (refereegranskat)abstract
    • Social distancing policies to ensure physical distance between people have become a crucial strategy in the battle against the spread of the coronavirus. The aim of this project is to analyze and compare social distancing policies implemented in Denmark and Sweden in 2020. Despite many similarities between the two countries, their response to the coronavirus pandemic differed markedly. Whereas authorities in Denmark initiated mandatory regulations and many severe restrictions, Swedish authorities predominantly promoted voluntary recommendations.
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31.
  • Norsker, Filippa Nyboe, et al. (författare)
  • Neurologic disorders in long-term survivors of neuroblastoma–a population-based cohort study within the Adult Life after Childhood Cancer in Scandinavia (ALiCCS) research program
  • 2020
  • Ingår i: Acta Oncologica. - 0284-186X. ; 59:2, s. 134-140
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Neuroblastoma is the commonest extracranial solid tumor of childhood, yet rare, and with poor survival before 1990, especially for high-risk disease; thus, information on late effects is sparse. With great advances in cancer treatment, survival has reached 80% in the Nordic countries. The aim of the study was to investigate the risk of developing neurologic disorders after neuroblastoma. Material and methods: Through population-based cancer registries of four Nordic countries we identified 654 5-year survivors of neuroblastoma (diagnosed 1959–2008) and 133,668 matched population comparisons. We grouped neurologic diagnoses from national hospital registries into 11 main diagnostic categories and 56 disease-specific sub-categories and calculated relative risks (RRs), absolute excess risks (AERs), cumulative incidence and mean cumulative count (MCC). Information on cancer treatment was available for 49% of survivors. Results: A hospital contact for a neurologic disorder was observed in 181 survivors 5 years or more from cancer diagnosis with 59 expected, yielding a RR of 3.1 (95% CI 2.7–3.6) and an AER of 16 per 1,000 person-years (95% CI 12–19). The most frequent disorders included epilepsy, paralytic syndromes, diseases of the eyes and ears and hearing loss. The cumulative incidence of any neurologic disorder was 31% in survivors 20 years after cancer diagnosis with a MCC of 0.5 unique diagnoses. All risks were highest in survivors of high-risk neuroblastoma. Conclusion: Neuroblastoma survivors represent a population with a high risk of developing neurologic disorders. Our results should contribute to improving health care planning and underscores the need for systematic follow-up care of this vulnerable group of survivors.
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32.
  • Norsker, Filippa Nyboe, et al. (författare)
  • Risk of late health effects after soft-tissue sarcomas in childhood–a population-based cohort study within the Adult Life after Childhood Cancer in Scandinavia research programme
  • 2020
  • Ingår i: Acta Oncologica. - 0284-186X. ; 59:10, s. 1-11
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: In the 1960s only 1/3 of children with soft-tissue sarcomas survived, however with improved treatments survival today has reached 70%. Given the previous poor survival and the rarity of soft-tissue sarcomas, the risk of somatic late effects in a large cohort of Nordic soft-tissue sarcoma survivors has not yet been assessed. Methods: In this population-based cohort study we identified 985 five-year soft-tissue sarcoma survivors in Nordic nationwide cancer registries and late effects in national hospital registries covering the period 1964–2012. Information on tumour site and radiotherapy was available for Danish and Finnish survivors (N = 531). Using disease-specific rates of first-time hospital contacts for somatic diseases in survivors and in 4,830 matched comparisons we calculated relative rates (RR) and rate differences (RD). Results: Survivors had a RR of 1.5 (95% CI 1.4–1.7) and an absolute RD of 23.5 (17.7–29.2) for a first hospital contact per 1,000 person-years. The highest risks in both relative and absolute terms were of endocrine disorders (RR = 2.5; RD = 7.6), and diseases of the nervous system (RR = 1.9; RD = 6.6), digestive organs (RR = 1.7; RD = 5.4) and urinary system (RR = 1.7; RD = 5.6). By tumour site, excess risk was lower after extremity tumours. Irradiated survivors had a 2.6 (1.2–5.9) times higher risk than non-irradiated. Conclusions: Soft-tissue sarcoma survivors have an increased risk of somatic late effects in 5 out of 10 main diagnostic groups of diseases, and the risk remains increased up to 40 years after cancer diagnosis. Risks were slightly lower for those treated for tumours in the extremities, and radiotherapy increased the risk by more than two-fold.
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33.
  • Olsen, Elisabeth K., et al. (författare)
  • Marine AChE inhibitors isolated from Geodia barretti : Natural compounds and their synthetic analogs
  • 2016
  • Ingår i: Organic and biomolecular chemistry. - : Royal Society of Chemistry. - 1477-0520 .- 1477-0539. ; 14:5, s. 1629-1640
  • Tidskriftsartikel (refereegranskat)abstract
    • Barettin, 8,9-dihydrobarettin, bromoconicamin and a novel brominated marine indole were isolated from the boreal sponge Geodia barretti collected off the Norwegian coast. The compounds were evaluated as inhibitors of electric eel acetylcholinesterase. Barettin and 8,9-dihydrobarettin displayed significant inhibition of the enzyme, with inhibition constants (Ki) of 29 and 19 μM respectively towards acetylcholinesterase via a reversible noncompetitive mechanism. These activities are comparable to those of several other natural acetylcholinesterase inhibitors of marine origin. Bromoconicamin was less potent against acetylcholinesterase, and the novel compound was inactive. Based on the inhibitory activity, a library of 22 simplified synthetic analogs was designed and prepared to probe the role of the brominated indole, common to all the isolated compounds. From the structure-activity investigation it was shown that the brominated indole motif is not sufficient to generate a high acetylcholinesterase inhibitory activity, even when combined with natural cationic ligands for the acetylcholinesterase active site. The four natural compounds were also analysed for their butyrylcholinesterase inhibitory activity in addition and shown to display comparable activities. The study illustrates how both barettin and 8,9-dihydrobarettin display additional bioactivities which may help to explain their biological role in the producing organism. The findings also provide new insights into the structure-activity relationship of both natural and synthetic acetylcholinesterase inhibitors.
  •  
34.
  • Pedersen, Britt Staevnsbo, et al. (författare)
  • Feasibility and implementation fidelity of a co-designed intervention to promote in-hospital mobility among older medical patients - the WALK-Copenhagen project (WALK-Cph)
  • 2022
  • Ingår i: Pilot and Feasibility Studies. - : BMC. - 2055-5784. ; 8:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Mobility interventions can prevent functional decline among older patients, but implementation of such interventions may be complicated by barriers in the clinical setting. The WALK-Copenhagen project (WALK-Cph) is aimed at promoting a 24-h mobility among older medical patients during hospitalization. The WALK-Cph intervention was co-designed by researchers and stakeholders to tailor the intervention to the clinical context. The aim of this study was to investigate the feasibility and implementation fidelity of the WALK-Cph intervention before evaluating clinical effectiveness in a randomized controlled trial (ClinicalTrials.gov NCT03825497). Methods: The WALK-Cph intervention consisted of six components: a welcome folder explaining the importance of in-hospital activity, a WALK-plan prescribing up to three daily walking sessions during and after hospitalization, a WALK-path in the hallway that patients were motivated to use daily, exercise posters in the hallways and bedrooms, self-service on beverages and clothes, and discharge with a WALK-plan. The present study reports on phase 2 of WALK-Cph and consists of a feasibility and a fidelity component. The study was conducted at the two WALK-Cph intervention departments after the initiation of the WALK-Cph intervention. A cohort of older medical patients (+65) was recruited for the feasibility study to assess recruitment and data collection procedures and the method for assessment of activity. Simultaneously, implementation fidelity was assessed by observing clinical practice and intervention delivery at the intervention departments. Results: A feasibility cohort of 48 patients was included. Inclusion was considered feasible with recruitment rates between 62% and 70% of all eligible patients. Also, data collection was conducted without obstacles, and all patients accepted to wear activity monitors. The fidelity observations showed that three of the six intervention components were partially implemented as planned whereas three components were not implemented as planned. Conclusion: The WALK-Cph intervention was found feasible, and although the intervention was not implemented with fidelity, the level of fidelity was considered sufficient to continue with further testing of the WALK-Cph intervention in a large-scale trial.
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35.
  • Pedersen, Camilla, et al. (författare)
  • Somatic disease in survivors of childhood malignant bone tumors in the nordic countries
  • 2021
  • Ingår i: Cancers. - : MDPI AG. - 2072-6694. ; 13:18
  • Tidskriftsartikel (refereegranskat)abstract
    • Survivors of malignant bone tumors in childhood are at risk of long-term adverse health effects. We comprehensively reviewed cases of somatic diseases that required a hospital contact in survivors of osteosarcoma and Ewing sarcoma. In a population-based cohort study, 620 five-year survivors of osteosarcoma (n = 440) or Ewing sarcoma (n = 180), diagnosed before the age of 20 years in Denmark, Finland, Iceland, and Sweden during 1943–2008, were followed in the national hospital registers. Overall rates of hospital contacts for any somatic disease and for 12 main diagnostic groups and 120 specific disease categories were compared with those in a matched comparison cohort (n = 3049) randomly selected from the national population registers. The rate of hospital contact for any somatic disease was 80% higher in survivors of malignant bone tumors than in comparisons and remained elevated up to 30 years after diagnosis. The rate of hospital contacts was higher after Ewing sarcoma (rate ratio (RR) 2.24; 95% confidence interval (CI) 1.76–2.85) than after osteosarcoma (RR 1.67; 95% CI 1.41–1.98). Elevated rates were observed for 11 main diagnostic groups, including infections, second malignant neoplasms, and diseases of the skin, bones, and circulatory, digestive, endocrine, and urinary systems. Survivors of malignant bone tumors in childhood are at increased risk of somatic diseases many years after diagnosis. This comprehensive study contributes new insight into the risk of late effects in survivors of osteosarcoma and Ewing sarcoma, which is an essential basis for optimal patient counseling and follow-up care.
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36.
  • Pyko, Andrei, et al. (författare)
  • Long-Term Exposure to Transportation Noise and Ischemic Heart Disease: A Pooled Analysis of Nine Scandinavian Cohorts.
  • 2023
  • Ingår i: Environmental health perspectives. - : Environmental Health Perspectives. - 1552-9924 .- 0091-6765. ; 131:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Transportation noise may induce cardiovascular disease, but the public health implications are unclear.The study aimed to assess exposure-response relationships for different transportation noise sources and ischemic heart disease (IHD), including subtypes.Pooled analyses were performed of nine cohorts from Denmark and Sweden, together including 132,801 subjects. Time-weighted long-term exposure to road, railway, and aircraft noise, as well as air pollution, was estimated based on residential histories. Hazard ratios (HRs) were calculated using Cox proportional hazards models following adjustment for lifestyle and socioeconomic risk factors.A total of 22,459 incident cases of IHD were identified during follow-up from national patient and mortality registers, including 7,682 cases of myocardial infarction. The adjusted HR for IHD was 1.03 [95% confidence interval (CI) 1.00, 1.05] per 10 dB Lden for both road and railway noise exposure during 5 y prior to the event. Higher risks were indicated for IHD excluding angina pectoris cases, with HRs of 1.06 (95% CI: 1.03, 1.08) and 1.05 (95% CI: 1.01, 1.08) per 10 dB Lden for road and railway noise, respectively. Corresponding HRs for myocardial infarction were 1.02 (95% CI: 0.99, 1.05) and 1.04 (95% CI: 0.99, 1.08). Increased risks were observed for aircraft noise but without clear exposure-response relations. A threshold at around 55 dB Lden was suggested in the exposure-response relation for road traffic noise and IHD.Exposure to road, railway, and aircraft noise in the prior 5 y was associated with an increased risk of IHD, particularly after exclusion of angina pectoris cases, which are less well identified in the registries. https://doi.org/10.1289/EHP10745.
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37.
  • Roswall, Nina, et al. (författare)
  • Long-Term Exposure to Transportation Noise and Risk of Incident Stroke : A Pooled Study of Nine Scandinavian Cohorts
  • 2021
  • Ingår i: Journal of Environmental Health Perspectives. - : National Institute of Environmental Health Sciences (NIEHS). - 0091-6765 .- 1552-9924. ; 129:10
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Transportation noise is increasingly acknowledged as a cardiovascular risk factor, but the evidence base for an association with stroke is sparse.Objective: We aimed to investigate the association between transportation noise and stroke incidence in a large Scandinavian population.Methods: We harmonized and pooled data from nine Scandinavian cohorts (seven Swedish, two Danish), totaling 135,951 participants. We identified residential address history and estimated road, railway, and aircraft noise for all addresses. Information on stroke incidence was acquired through linkage to national patient and mortality registries. We analyzed data using Cox proportional hazards models, including socioeconomic and lifestyle confounders, and air pollution.Results: During follow-up (median=19.5y), 11,056 stroke cases were identified. Road traffic noise (Lden) was associated with risk of stroke, with a hazard ratio (HR) of 1.06 [95% confidence interval (CI): 1.03, 1.08] per 10-dB higher 5-y mean time-weighted exposure in analyses adjusted for individual- and area-level socioeconomic covariates. The association was approximately linear and persisted after adjustment for air pollution [particulate matter (PM) with an aerodynamic diameter of ≤2.5μm (PM2.5) and NO2]. Stroke was associated with moderate levels of 5-y aircraft noise exposure (40–50 vs. ≤40 dB) (HR=1.12; 95% CI: 0.99, 1.27), but not with higher exposure (≥50 dB, HR=0.94HR; 95% CI: 0.79, 1.11). Railway noise was not associated with stroke.Discussion: In this pooled study, road traffic noise was associated with a higher risk of stroke. This finding supports road traffic noise as an important cardiovascular risk factor that should be included when estimating the burden of disease due to traffic noise.
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38.
  • Schunkert, Heribert, et al. (författare)
  • Large-scale association analysis identifies 13 new susceptibility loci for coronary artery disease
  • 2011
  • Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 43:4, s. 153-333
  • Tidskriftsartikel (refereegranskat)abstract
    • We performed a meta-analysis of 14 genome-wide association studies of coronary artery disease (CAD) comprising 22,233 individuals with CAD (cases) and 64,762 controls of European descent followed by genotyping of top association signals in 56,682 additional individuals. This analysis identified 13 loci newly associated with CAD at P < 5 x 10(-8) and confirmed the association of 10 of 12 previously reported CAD loci. The 13 new loci showed risk allele frequencies ranging from 0.13 to 0.91 and were associated with a 6% to 17% increase in the risk of CAD per allele. Notably, only three of the new loci showed significant association with traditional CAD risk factors and the majority lie in gene regions not previously implicated in the pathogenesis of CAD. Finally, five of the new CAD risk loci appear to have pleiotropic effects, showing strong association with various other human diseases or traits.
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39.
  • Seing, Ida, 1982-, et al. (författare)
  • Social Distancing Policies in the Coronavirus Battle : A Comparison of Denmark and Sweden
  • 2021
  • Ingår i: International Journal of Environmental Research and Public Health. - : MDPI. - 1661-7827 .- 1660-4601. ; 18:20
  • Tidskriftsartikel (refereegranskat)abstract
    • Social distancing measures have been a key component in government strategies to mitigate COVID-19 globally. Based on official documents, this study aimed to identify, compare and analyse public social distancing policy measures adopted in Denmark and Sweden regarding the coronavirus from 1 March 2020 until 1 October 2020. A key difference was the greater emphasis on laws and executive orders (sticks) in Denmark, which allowed the country to adopt many stricter policy measures than Sweden, which relied mostly on general guidelines and recommendations (sermons). The main policy adopters in Denmark were the government and the Danish Parliament, whereas the Public Health Agency issued most policies in Sweden, reflecting a difference in political governance and administrative structure in the two countries. During the study period, Sweden had noticeably higher rates of COVID-19 deaths and hospitalizations per 100,000 population than Denmark, yet it is difficult to determine the impact or relative effectiveness of sermons and sticks, particularly with regard to broader and longer-term health, economic and societal effects.
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40.
  • So, Rina, et al. (författare)
  • Long-term exposure to air pollution and liver cancer incidence in six European cohorts
  • 2021
  • Ingår i: International Journal of Cancer. - : Wiley. - 0020-7136 .- 1097-0215. ; 149:11, s. 1887-1897
  • Tidskriftsartikel (refereegranskat)abstract
    • Particulate matter air pollution and diesel engine exhaust have been classified as carcinogenic for lung cancer, yet few studies have explored associations with liver cancer. We used six European adult cohorts which were recruited between 1985 and 2005, pooled within the Effects of low-level air pollution: A study in Europe (ELAPSE) project, and followed for the incidence of liver cancer until 2011 to 2015. The annual average exposure to nitrogen dioxide (NO2), particulate matter with diameter <2.5 mu m (PM2.5), black carbon (BC), warm-season ozone (O-3), and eight elemental components of PM2.5 (copper, iron, zinc, sulfur, nickel, vanadium, silicon, and potassium) were estimated by European-wide hybrid land-use regression models at participants' residential addresses. We analyzed the association between air pollution and liver cancer incidence by Cox proportional hazards models adjusting for potential confounders. Of 330 064 cancer-free adults at baseline, 512 developed liver cancer during a mean follow-up of 18.1 years. We observed positive linear associations between NO2 (hazard ratio, 95% confidence interval: 1.17, 1.02-1.35 per 10 mu g/m(3)), PM2.5 (1.12, 0.92-1.36 per 5 mu g/m(3)), and BC (1.15, 1.00-1.33 per 0.5 10(-5)/m) and liver cancer incidence. Associations with NO2 and BC persisted in two-pollutant models with PM2.5. Most components of PM2.5 were associated with the risk of liver cancer, with the strongest associations for sulfur and vanadium, which were robust to adjustment for PM2.5 or NO2. Our study suggests that ambient air pollution may increase the risk of liver cancer, even at concentrations below current EU standards.
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41.
  • Stafoggia, Massimo, et al. (författare)
  • Long-term exposure to low ambient air pollution concentrations and mortality among 28 million people : results from seven large European cohorts within the ELAPSE project
  • 2022
  • Ingår i: The Lancet Planetary Health. - : Elsevier B.V.. - 2542-5196. ; 6:1, s. e9-e18
  • Tidskriftsartikel (refereegranskat)abstract
    • Background Long-term exposure to ambient air pollution has been associated with premature mortality, but associations at concentrations lower than current annual limit values are uncertain. We analysed associations between low-level air pollution and mortality within the multicentre study Effects of Low-Level Air Pollution: A Study in Europe (ELAPSE).Methods In this multicentre longitudinal study, we analysed seven population-based cohorts of adults (age ≥30 years) within ELAPSE, from Belgium, Denmark, England, the Netherlands, Norway, Rome (Italy), and Switzerland (enrolled in 2000–11; follow-up until 2011–17). Mortality registries were used to extract the underlying cause of death for deceased individuals. Annual average concentrations of fine particulate matter (PM2·5), nitrogen dioxide (NO2), black carbon, and tropospheric warm-season ozone (O3) from Europe-wide land use regression models at 100 m spatial resolution were assigned to baseline residential addresses. We applied cohort-specific Cox proportional hazard models with adjustment for area-level and individual-level covariates to evaluate associations with non-accidental mortality, as the main outcome, and with cardiovascular, non-malignant respiratory, and lung cancer mortality. Subset analyses of participants living at low pollutant concentrations (as per predefined values) and natural splines were used to investigate the concentration-response function. Cohort-specific effect estimates were pooled in a random-effects meta-analysis.Findings We analysed 28 153 138 participants contributing 257 859 621 person-years of observation, during which 3 593 741 deaths from non-accidental causes occurred. We found significant positive associations between non-accidental mortality and PM2·5, NO2, and black carbon, with a hazard ratio (HR) of 1·053 (95% CI 1·021–1·085) per 5 μg/m3 increment in PM2·5, 1·044 (1·019–1·069) per 10 μg/m3 NO2, and 1·039 (1·018–1·059) per 0·5 × 10−5/m black carbon. Associations with PM2·5, NO2, and black carbon were slightly weaker for cardiovascular mortality, similar for non-malignant respiratory mortality, and stronger for lung cancer mortality. Warm-season O3 was negatively associated with both non-accidental and cause-specific mortality. Associations were stronger at low concentrations: HRs for non-accidental mortality at concentrations lower than the WHO 2005 air quality guideline values for PM2·5 (10 μg/m3) and NO2 (40 μg/m3) were 1·078 (1·046–1·111) per 5 μg/m3 PM2·5 and 1·049 (1·024–1·075) per 10 μg/m3 NO2. Similarly, the association between black carbon and non-accidental mortality was highest at low concentrations, with a HR of 1·061 (1·032–1·092) for exposure lower than 1·5× 10−5/m, and 1·081 (0·966–1·210) for exposure lower than 1·0× 10−5/m.Interpretation Long-term exposure to concentrations of PM2·5 and NO2 lower than current annual limit values was associated with non-accidental, cardiovascular, non-malignant respiratory, and lung cancer mortality in seven large European cohorts. Continuing research on the effects of low concentrations of air pollutants is expected to further inform the process of setting air quality standards in Europe and other global regions.
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42.
  • Stefansdottir, Nina Thorny, et al. (författare)
  • Implementing a new emergency department : a qualitative study of health professionals change responses and perceptions
  • 2022
  • Ingår i: BMC Health Services Research. - : BMC. - 1472-6963. ; 22:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Background The aim of the study is two-fold. It explores how managers and key employees at the Emergency Department (ED) and specialist departments in a university hospital in the Capital Region of Denmark respond to the planned change to a new ED, and how they perceive the change involved in the implementation of the new ED. The study investigates what happens when health professionals are confronted with implementation of policy that changes their organization and everyday work lives. Few studies provide in-depth investigations of health professionals reactions to the implementation of new EDs, and particularly how they influence the implementation of a nationwide organizational change framed within a political strategy. Methods The study used semi-structured individual interviews with 51 health professionals involved in implementation activities related to an organizational change of establishing a new ED with new patient pathways for acutely ill patients. The data was deductively analyzed using Leon Coetsees theoretical framework of change responses, but the analysis also allowed for a more inductive reading of the material. Results Fourteen types of responses to establishing a new ED were identified and mapped onto six of the seven overall change responses in Coetsees framework. The participants perceived the change as particularly three changes. Firstly, they wished to create the best possible acute patient pathway in relation to their specialty. Whether the planned new ED would redeem this was disputed. Secondly, participants perceived the change as relocation to a new building, which both posed potentials and worries. Thirdly, both hopeful and frustrated statements were given about the newly established medical specialty of emergency medicine (EM), which was connected to the success of the new ED. Conclusions The study showcases how implementation processes within health care are not straightforward and that it is not only the content of the implementation that determines the success of the implementation and its outcomes but also how these are perceived by managers and employees responsible for the process and their context. In this way, managers must recognize that it cannot be pre-determined how implementation will proceed, which necessitates fluid implementation plans and demands implementation managements skills.
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43.
  • Stefansdottir, Nina Thorny, et al. (författare)
  • Young adults' perceptions of information on social distancing measures and everyday life during the COVID-19 pandemic in Denmark and Sweden: an interview study
  • 2024
  • Ingår i: International Journal of Adolescence and Youth. - : ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD. - 0267-3843 .- 2164-4527. ; 29:1
  • Tidskriftsartikel (refereegranskat)abstract
    • With the outbreak of the COVID-19 pandemic, Denmark and Sweden's governments and health authorities implemented social distancing measures as the main strategy to limit the spread of the coronavirus. In Denmark, these were mostly mandatory, whereas in Sweden they were primarily voluntarily based. The aim of this study was to explore how young adults in Denmark and Sweden retrieved and perceived information during the COVID-19 pandemic and what their experiences of everyday life were with the implemented social distancing measures. To this end, 30 Danish and Swedish young adults between 18 and 25 years were interviewed. The participants considered themselves informed and reflected on multiple sources of information. However, social distancing measures were translated in different ways and had both negative and positive implications for their everyday lives. Many participants felt that their youth - as a significant phase in life - became restricted.
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44.
  • Stormlund, Sacha, et al. (författare)
  • The prevalence of late-follicular phase progesterone elevation and impact on the ongoing pregnancy rate after fresh and frozen blastocyst transfer. Sub-study of an RCT
  • 2024
  • Ingår i: HUMAN FERTILITY. - 1464-7273 .- 1742-8149. ; 27:1
  • Tidskriftsartikel (refereegranskat)abstract
    • The effect of late-follicular phase progesterone elevation (LFPE) during ovarian stimulation on reproductive outcomes in ART treatment remains controversial, but recent studies indicate lower pregnancy rates with rising progesterone levels. This study aims to investigate the prevalence of late-follicular phase progesterone elevation (LFPE) and possible impact on ongoing pregnancy rate after fresh or frozen blastocyst transfer in a sub-study setting of a randomised controlled trial. A total of 288 women were included (n=137 and n=151 in the fresh transfer and freeze-all group, respectively). Among these 11(3.8%) had a progesterone level >= 1.5 ng/ml, and 20(6.9%) had a progesterone level >= 1.2 ng/ml on trigger day. Spline regression analysis showed no significant effect of late follicular phase progesterone levels on ongoing pregnancy. In the multivariate regression analysis (n = 312) only age, but not progesterone level on trigger day was significantly associated with ongoing pregnancy. In conclusion, in a clinical setting with moderate gonadotrophin stimulation and well-defined trigger and fresh transfer cancellation criteria, the prevalence of women with LFPE >= 1.5 ng/ml was low and did not indicate the clinical value of routine measurement of progesterone in the late follicular phase.
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45.
  • Sällfors-Holmqvist, Anna, et al. (författare)
  • Adult Life after Childhood Cancer in Scandinavia: Diabetes mellitus following treatment for cancer in childhood.
  • 2014
  • Ingår i: European Journal of Cancer. - : Elsevier BV. - 1879-0852 .- 0959-8049. ; 50:6, s. 1169-1175
  • Tidskriftsartikel (refereegranskat)abstract
    • An increased risk for diabetes mellitus (DM) adds significantly to the burden of late complications in childhood cancer survivors. Complications of DM may be prevented by using appropriate screening. It is, therefore, important to better characterise the reported increased risk for DM in a large population-based setting.
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