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1.
  • Brown, Rosemary, 1990, et al. (författare)
  • Plasma-Induced Heating Effects on Platinum Nanoparticle Size during Sputter Deposition Synthesis in Polymer and Ionic Liquid Substrates
  • 2021
  • Ingår i: Langmuir. - : American Chemical Society (ACS). - 1520-5827 .- 0743-7463. ; 37:29, s. 8821-8828
  • Tidskriftsartikel (refereegranskat)abstract
    • Nanoparticle catalyst materials are becoming ever more important in a sustainable future. Specifically, platinum (Pt) nanoparticles have relevance in catalysis, in particular, fuel cell technologies. Sputter deposition into liquid substrates has been shown to produce nanoparticles without the presence of air and other contaminants and the need for precursors. Here, we produce Pt nanoparticles in three imidazolium-based ionic liquids and PEG 600. All Pt nanoparticles are crystalline and around 2 nm in diameter. We show that while temperature has an effect on particle size for Pt, it is not as great as for other materials. Sputtering power, time, and postheat treatment all show slight influence on the particle size, indicating the importance of temperature during sputtering. The temperature of the liquid substrate is measured and reaches over 150 °C during deposition which is found to increase the particle size by less than 20%, which is small compared to the effect of temperature on Au nanoparticles presented in the literature. High temperatures during Pt sputtering are beneficial for increasing Pt nanoparticle size beyond 2 nm. Better temperature control would allow for more control over the particle size in the future.
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2.
  • Christensen, Alex Hørby, et al. (författare)
  • Complications of implantable cardioverter-defibrillator treatment in arrhythmogenic right ventricular cardiomyopathy
  • 2022
  • Ingår i: Europace. - : Oxford University Press (OUP). - 1099-5129 .- 1532-2092. ; 24:2, s. 306-312
  • Tidskriftsartikel (refereegranskat)abstract
    • Aims: Treatment with implantable cardioverter-defibrillators (ICD) is a cornerstone for prevention of sudden cardiac death in arrhythmogenic right ventricular cardiomyopathy (ARVC). We aimed at describing the complications associated with ICD treatment in a multinational cohort with long-term follow-up. Methods and results: The Nordic ARVC registry was established in 2010 and encompasses a large multinational cohort of ARVC patients, including their clinical characteristics, treatment, and events during follow-up. We included 299 patients (66% males, median age 41 years). During a median follow-up of 10.6 years, 124 (41%) patients experienced appropriate ICD shock therapy, 28 (9%) experienced inappropriate shocks, 82 (27%) had a complication requiring surgery (mainly lead-related, n = 75), and 99 (33%) patients experienced the combined endpoint of either an inappropriate shock or a surgical complication. The crude rate of first inappropriate shock was 3.4% during the first year after implantation but decreased after the first year and plateaued over time. Contrary, the risk of a complication requiring surgery was 5.5% the first year and remained high throughout the study period. The combined risk of any complication was 7.9% the first year. In multivariate cox regression, presence of atrial fibrillation/flutter was a risk factor for inappropriate shock (P < 0.05), whereas sex, age at implant, and device type were not (all P > 0.05). Conclusion: Forty-one percent of ARVC patients treated with ICD experienced potentially life-saving ICD therapy during long-term follow-up. A third of the patients experienced a complication during follow-up with lead-related complications constituting the vast majority.
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3.
  • Christensen, Alex Hörby, et al. (författare)
  • Genotype-phenotype correlation in arrhythmogenic right ventricular cardiomyopathy-risk of arrhythmias and heart failure.
  • 2021
  • Ingår i: Journal of medical genetics. - : BMJ PUBLISHING GROUP. - 1468-6244 .- 0022-2593.
  • Tidskriftsartikel (refereegranskat)abstract
    • Arrhythmogenic right ventricular cardiomyopathy (ARVC) is predominantly caused by desmosomal genetic variants, and clinical hallmarks include arrhythmias and systolic dysfunction. We aimed at studying the impact of the implicated gene(s) on the disease course.The Nordic ARVC Registry holds data on a multinational cohort of ARVC families. The effects of genotype on electrocardiographic features, imaging findings and clinical events were analysed.We evaluated 419 patients (55% men), with a mean follow-up of 11.2±7.4 years. A pathogenic desmosomal variant was identified in 62% of the 230 families: PKP2 in 41%, DSG2 in 13%, DSP in 7% and DSC2 in 3%. Reduced left ventricular ejection fraction (LVEF) ≤45% on cardiac MRI was more frequent among patients with DSC2/DSG2/DSP than PKP2 ARVC (27% vs 4%, p<0.01). In contrast, in Cox regression modelling of patients with definite ARVC, we found a higher risk of arrhythmias among PKP2 than DSC2/DSG2/DSP carriers: HR 0.25 (0.10-0.68, p<0.01) for atrial fibrillation/flutter, HR 0.67 (0.44-1.0, p=0.06) for ventricular arrhythmias and HR 0.63 (0.42-0.95, p<0.05) for any arrhythmia. Gene-negative patients had an intermediate risk (16%) of LVEF ≤45% and a risk of the combined arrhythmic endpoint comparable with DSC2/DSG2/DSP carriers. Male sex was a risk factor for both arrhythmias and reduced LVEF across all genotype groups (p<0.01).In this large cohort of ARVC families with long-term follow-up, we found PKP2 genotype to be more arrhythmic than DSC2/DSG2/DSP or gene-negative carrier status, whereas reduced LVEF was mostly seen among DSC2/DSG2/DSP carriers. Male sex was associated with a more severe phenotype.
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4.
  • Christensen, Alex Horby, et al. (författare)
  • Genotype-phenotype correlation in arrhythmogenic right ventricular cardiomyopathy-risk of arrhythmias and heart failure
  • 2022
  • Ingår i: Journal of Medical Genetics. - : BMJ PUBLISHING GROUP. - 0022-2593 .- 1468-6244. ; 59:9, s. 858-864
  • Tidskriftsartikel (refereegranskat)abstract
    • Background Arrhythmogenic right ventricular cardiomyopathy (ARVC) is predominantly caused by desmosomal genetic variants, and clinical hallmarks include arrhythmias and systolic dysfunction. We aimed at studying the impact of the implicated gene(s) on the disease course. Methods The Nordic ARVC Registry holds data on a multinational cohort of ARVC families. The effects of genotype on electrocardiographic features, imaging findings and clinical events were analysed. Results We evaluated 419 patients (55% men), with a mean follow-up of 11.2 +/- 7.4 years. A pathogenic desmosomal variant was identified in 62% of the 230 families: PKP2 in 41%, DSG2 in 13%, DSP in 7% and DSC2 in 3%. Reduced left ventricular ejection fraction (LVEF) <= 45% on cardiac MRI was more frequent among patients with DSC2/DSG2/DSP than PKP2 ARVC (27% vs 4%, p<0.01). In contrast, in Cox regression modelling of patients with definite ARVC, we found a higher risk of arrhythmias among PKP2 than DSC2/DSG2/DSP carriers: HR 0.25 (0.10-0.68, p<0.01) for atrial fibrillation/flutter, HR 0.67 (0.44-1.0, p=0.06) for ventricular arrhythmias and HR 0.63 (0.42-0.95, p<0.05) for any arrhythmia. Gene-negative patients had an intermediate risk (16%) of LVEF <= 45% and a risk of the combined arrhythmic endpoint comparable with DSC2/DSG2/DSP carriers. Male sex was a risk factor for both arrhythmias and reduced LVEF across all genotype groups (p<0.01). Conclusion In this large cohort of ARVC families with long-term follow-up, we found PKP2 genotype to be more arrhythmic than DSC2/DSG2/DSP or gene-negative carrier status, whereas reduced LVEF was mostly seen among DSC2/DSG2/DSP carriers. Male sex was associated with a more severe phenotype.
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5.
  • Christensen, Sarah Friis, et al. (författare)
  • Healthcare resource utilization in patients with myeloproliferative neoplasms: A Danish nationwide matched cohort study
  • 2022
  • Ingår i: European Journal of Haematology. - : John Wiley & Sons. - 0902-4441 .- 1600-0609.
  • Tidskriftsartikel (refereegranskat)abstract
    • Few studies have assessed healthcare resource utilization (HRU) in patients with Philadelphia-negative myeloproliferative neoplasms (MPN) using a matched cohort design. Further, no detailed assessment of HRU in the years preceding an MPN diagnosis exists. We conducted a registry-based nationwide Danish cohort study, including patients with essential thrombocythemia, polycythemia vera, myelofibrosis, and unclassifiable MPN diagnosed between January 2010 and December 2016. HRU data were summarized annually from 2 years before MPN diagnosis until emigration, death, or end of study (December 2017). We included 3342 MPN patients and 32 737 comparisons without an MPN diagnosis, matched on sex, age, region of residence, and level of education. During the study period, the difference in HRU (rate ratio) between patients and matched comparisons ranged from 1.0 to 1.5 for general practitioner contacts, 0.9 to 2.2 for hospitalizations, 0.9 to 3.8 for inpatient days, 1.0 to 4.0 for outpatient visits, 1.3 to 2.1 for emergency department visits, and 1.0 to 4.1 for treatments/examinations. In conclusion, MPN patients had overall higher HRU than the matched comparisons throughout the follow-up period (maximum 8 years). Further, MPN patients had substantially increased HRU in both the primary and secondary healthcare sector in the 2 years preceding the diagnosis.
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6.
  • Christensen, Sarah Friis, et al. (författare)
  • Labor Market Attachment in Patients with Myeloproliferative Neoplasms: A Nationwide Matched Cohort Study
  • 2021
  • Ingår i: Blood. - : American Society of Hematology. - 0006-4971 .- 1528-0020. ; 138:Suppl 1
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Myeloproliferative neoplasms (MPNs) are characterized by a substantial symptom burden, risk of debilitating complications (e.g., thrombosis), and increased comorbidity. Recently, three comprehensive questionnaire studies (Mesa 2016, Harrison 2017, Jingbo 2018) have reported a high impact of MPNs on patients' ability to work. However, no registry-based studies have assessed labor market attachment (LMA) of MPN patients and matched nonMPN comparisons.AIM: To assess the pre- and post-diagnostic LMA of MPN patients and matched nonMPN comparisons.METHODS: We conducted a descriptive, registry-based nationwide cohort study, using data from the Danish National Chronic Myeloid Neoplasia Registry including all Danish MPN patients diagnosed between January 2010 and December 2016. Population-based cohorts of nonMPN comparisons were constructed by 1:10 matching on age, sex, level of education, and region of residence. Data on LMA were retrieved from the Danish Register for Evaluation of Marginalization, which holds information on all public transfer payments in Denmark. Data were linked using the unique civil registration number, which identifies all Danish citizens. The LMA endpoints were defined for each individual as working (not receiving any type of transfer payment), unemployed, receiving transfer payment for either sick leave, disability pension, age pension, or other health-related benefits (e.g., wage-subsidized employment). We assessed LMA weekly for each individual from two years before diagnosis until death, emigration, or two years after the diagnosis. For each cohort, we presented LMA as proportions with 95% confidence intervals (CIs), as well as the proportion of individuals who died during follow-up.RESULTS: The study included 3,342 MPN patients (1,140 essential thrombocythemia [ET]; 1,109 polycythemia vera [PV]; 533 myelofibrosis [MF]; and 560 unspecified MPN [MPN-U]) and 32,737 nonMPN comparisons (11,181 nonET; 10,873 nonPV; 5,217 nonPMF; and 5,466 nonMPN-U). The median age at time of diagnosis was: ET 67 years (interquartile range [IQR], 55-76); PV, 69 years (IQR, 61-77); PMF, 73 years (IQR, 66-79); and MPN-U, 72 years (IQR, 63-80).At time of MPN diagnosis, the majority of MPN patients and nonMPN comparisons received age pension (range: ET, 52.1% [95% CI, 49.2-55.0] to nonMF, 70.3% [95% CI, 69.1-71.6]). The proportions working were: ET, 35.1% (95% CI, 32.3-37.9) vs. nonET, 37.3% (95% CI, 36.5-38.2); PV, 22.6% (95% CI, 20.2-25.1) vs. nonPV, 30.8% (95% CI, 29.9-31.7); MF, 23.8% (95% CI, 20.2-27.4) vs. nonMF, 23.6% (95% CI, 22.5-24.8); and MPN-U, 22.1% (95% CI,18.7- 25.6) vs. nonMPN-U, 27.8% (95% CI, 26.6-29.0). Across MPN subtypes, a larger proportion of patients than comparisons were on sick leave: ET, 3.5% (95% CI, 2.4-4.6) vs. nonET, 1.3% (95% CI, 1.1-1.5); PV, 5.5% (95% CI, 4.2-6.8) vs. nonPV, 0.9% (95% CI, 0.7-1.1); MF (not applicable due to small numbers) vs. nonMF, 0.6% (95% CI, 0.4-0.8); and MPN-U, 3.0% (95% CI, 1.6- 4.5) vs. nonMPN-U, 1.0% (95% CI, 0.7-1.3). Regarding disability pension, the proportions ranged from 4.1% (95% CI, 2.4-5.8) to 5.0% (95% CI, 3.7-6.3) among patients and from 3.1% (95% CI, 2.6-3.6) to 4.7% (95% CI, 4.3-5.1) among comparisons. For both MPN patients and nonMPN comparisons, few were unemployed (≤3.3%) or received other health-related benefits (≤1.6%).Two years preceding diagnosis, the proportion of PV and MPN-U patients working was slightly lower than the matched comparisons: PV, 31.0% (95% CI, 28.4-33.8) vs. nonPV, 34.3% (95% CI, 33.5-35.2) and MPN-U, 28.2% (95% CI, 24.6-32.1) vs. nonMPN-U, 32.0% (95% CI, 30.7-33.2), while this difference was not observed between ET and MF patients and their respective comparisons.From two years before to two years after diagnosis, we observed slightly larger reductions in the proportion working among MPN patients than among comparisons. Among MPN patients, the proportion on sick leave including other health-related benefits, increased during the study period, while it remained unchanged among comparisons. The proportion of patients and comparisons on disability pension remained stable.CONCLUSION: Overall, our findings showed that Danish patients with ET, PV, MF, and MPN-U had slightly impaired LMA already two years before diagnosis and up to two years after diagnosis. Thus, fewer patients were working and more patients transferred to sick leave compared with matched individuals without MPN.
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7.
  • Christensen, Sarah, et al. (författare)
  • Healthcare resource utilization in patients with myeloproliferative neoplasms: a nationwide matched cohort study
  • 2021
  • Ingår i: HemaSphere. - : Ovid Technologies (Wolters Kluwer Health). - 2572-9241. ; 5:S2, s. 529-530
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Myeloproliferative neoplasms (MPNs) are associated with severe complications and a substantial symptom burden – frequently emerging several years before diagnosis. Due to the chronic nature ofthe diseases, MPN patients have a lifelong need for treatment and care. However, only few studies have assessed MPN healthcare resource utilization (HRU) compared with matched cohorts, and no detailed assessments of HRU in the years preceding MPN diagnosis exist.Aims: To assess the pre- and post-diagnostic HRU of MPN patients compared with matched cohorts of nonMPN comparisons.Methods: We conducted this descriptive, register-based nationwide cohort study, utilizing data from the Danish National Chronic Myeloid Neoplasia Registry on all MPN patients diagnosed between January 2010 and December 2016, and data on HRU from the Danish National Patient Registry and the Danish National Health Service Registry. Populationbased cohorts of nonMPN comparisons were constructed by 1:10 matchingon age, sex, level of education, and region of residence. Data were linkedusing the unique civil registration number, which identifies all Danish citizens. HRU was summarized over each year for all cohorts from twoyears before date of MPN diagnosis and until emigration, death, or endof study (31 December 2017). HRU was calculated as annual number ofhealthcare contacts (inpatient days, outpatient consultations, treatmentsand examinations, and general practitioner [GP] visits) divided by person-years at risk and compared using rate ratios with 95% CI.Results: The study population included 3,342 MPN patients (1,140 essential thrombocythemia [ET]; 1,109 polycythemia vera [PV]; 533 primary myelofibrosis [PMF]; and 560 unspecified MPN [MPN-U]) and 32,737 nonMPN comparisons (11,181 nonET; 10,873 nonPV; 5,217 nonPMF; and 5,466 nonMPN-U). The median age was 67 (ET), 69 (PV), 73 (PMF), and 72 years (MPN-U), and the mean follow-up was 3.8 (ET), 3.8(PV), 3.1 (PMF), and 3.3 years (MPN-U). A total of 750 (22.4%) MPNpatients and 4,627 (14.1%) nonMPN comparisons died during follow-up.In nearly all years of follow-up, MPN patients had a higher HRU thannonMPN comparisons (Figure, rate ratio>1). Rate ratios for outpatientconsultations were largest at the time of diagnosis: ET, 2.7 (95%CI, 2.6-2.9); PV, 3.4 (95%CI, 3.2-3.6); PMF, 4.0 (95%CI, 3.7-4.4); and MPN-U,3.7 (95%CI, 3.4-4.0). For most MPN subtypes, rate ratios also peaked attime of diagnosis for treatment and examinations. In contrast, the largest rate ratio for PV was in the last year of follow-up: 3.5 (95%CI, 2.8-4.3). Across MPN subtypes, rate ratios for GP visits varied from 1.0 to1.5 during follow-up without any considerable fluctuations. Interestingly, increased rate ratios for inpatients days were evident 2 years before diagnosis: ET, 1.8 (95%CI, 1.7-1.9); PV, 1.3, (95%CI, 1.2-1.3); PMF, 1.4(95%CI, 1.2-1.5); and MPN-U, 1.7 (95%CI, 1.6-1.9). During follow-up,notable increases in rate ratios were observed, e.g., PMF 3.0 (95%CI 2.4-3.6) and PV 3.8 (95%CI 3.0-4.8) in year 5 and 7, respectively.Summary/Conclusion: Overall, compared with matched nonMPN comparisons, MPN patients had a higher HRU throughout the study period. This was consistent across MPN subtypes and HRU measures. Within the limitations of small numbers toward end of follow-up and lack ofmatching on comorbidity, our findings confirmed a consistent HRU burden after MPN diagnosis. Equally important, our study revealed substantial increases in HRU two years before MPN diagnosis, warrantingfurther exploration of the pre-diagnostic period, including the potentialbenefits of early detection.
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8.
  • Eichhorst, B., et al. (författare)
  • First-Line Venetoclax Combinations in Chronic Lymphocytic Leukemia.
  • 2023
  • Ingår i: New England Journal of Medicine. - : MASSACHUSETTS MEDICAL SOC. - 0028-4793 .- 1533-4406. ; 388:19, s. 1739-1754
  • Tidskriftsartikel (refereegranskat)abstract
    • Background Randomized trials of venetoclax plus anti-CD20 antibodies as first-line treatment in fit patients (i.e., those with a low burden of coexisting conditions) with advanced chronic lymphocytic leukemia (CLL) have been lacking. Methods In a phase 3, open-label trial, we randomly assigned, in a 1:1:1:1 ratio, fit patients with CLL who did not have TP53 aberrations to receive six cycles of chemoimmunotherapy (fludarabine-cyclophosphamide-rituximab or bendamustine-rituximab) or 12 cycles of venetoclax-rituximab, venetoclax-obinutuzumab, or venetoclax-obinutuzumab-ibrutinib. Ibrutinib was discontinued after two consecutive measurements of undetectable minimal residual disease or could be extended. The primary end points were undetectable minimal residual disease (sensitivity,
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9.
  • Frederiksen, Kristian Steen, et al. (författare)
  • Focusing on Earlier Management of Alzheimer Disease: Expert Opinion Based on a Modified Nominal Group Technique.
  • 2024
  • Ingår i: Alzheimer disease and associated disorders. - 1546-4156. ; 38:1, s. 1-7
  • Tidskriftsartikel (refereegranskat)abstract
    • Despite the number of people living with Alzheimer disease (AD), awareness of the early stages of this condition, including mild cognitive impairment due to AD-which poses management challenges-continues to be low. To identify areas for improvement in early AD management, dementia specialists convened in a virtual roundtable meeting.A modified version of the nominal group technique was followed to prioritize specific topics and allow experts to provide their opinions. The overarching topics prioritized and discussed were (1) education and support for primary care physicians on cognitive assessment, detection of mild cognitive impairment, and patient monitoring; (2) nonpharmacological interventions; (3) and the introduction of disease-modifying therapies.Consensus was achieved regarding the need for educating primary care physicians on identifying people with cognitive impairment and for better diagnostic tools for its detection and early management. Management of mild cognitive impairment due to AD should encompass an adequate follow-up schedule aiming to maintain function for as long as possible, and primary care physicians and patients should be aware of the benefits of nonpharmacological interventions.
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10.
  • 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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