| 1. |
- Kaufmann, Tobias, et al.
(författare)
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Common brain disorders are associated with heritable patterns of apparent aging of the brain
- 2019
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Ingår i: Nature Neuroscience. - : Nature Publishing Group. - 1097-6256 .- 1546-1726. ; 22:10, s. 1617-
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Tidskriftsartikel (refereegranskat)abstract
- Common risk factors for psychiatric and other brain disorders are likely to converge on biological pathways influencing the development and maintenance of brain structure and function across life. Using structural MRI data from 45,615 individuals aged 3-96 years, we demonstrate distinct patterns of apparent brain aging in several brain disorders and reveal genetic pleiotropy between apparent brain aging in healthy individuals and common brain disorders.
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| 2. |
- Lockmer, Sandra, et al.
(författare)
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Chemotherapy-Free Initial Treatment of Advanced Indolent Lymphoma Has Durable Effect With Low Toxicity : Results From Two Nordic Lymphoma Group Trials With More Than 10 Years of Follow-Up
- 2018
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Ingår i: Journal of Clinical Oncology. - 0732-183X .- 1527-7755. ; 36:33, s. 3315-3323
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: For indolent lymphoma, the optimal timing, sequence, and choice of therapeutic regimens remain a matter of debate. In two Nordic Lymphoma Group randomized trials, symptomatic or clearly progressing patients were treated first line with a rituximab-containing regimen without chemotherapy. The purpose of this study was to assess long-term survival, risk of transformation, and need of new therapies.Methods: Data were collected at cross-sectional follow-up for 321 patients with indolent lymphoma (84% with follicular lymphomas [FL]) included in one of two Nordic Lymphoma Group trials (accrual 1998 to 1999 and 2002 to 2008). All patients received first-line therapy with one or two cycles of four weekly infusions of rituximab 375 mg/m(2), and 148 were randomly allocated to the addition of interferon alfa-2a. Follow-up data were retrieved from initial trial databases and medical records on repeated clinical evaluations.Results: At the end of follow-up, 73% of patients were alive, with a median follow-up after random assignment of 10.6 years. Among all, 36% (38% with FL) had never needed chemotherapy. For patients with FL who required new therapy within 24 months because of early disease progression, the 10-year survival rate was 59% versus 81% for those with longer remission. Interferon was not shown to improve long-term outcome. Transformation was diagnosed in 20% of all patients (2.4% per person-year) and in 18% with FL. An additional malignancy was found in 12%.Conclusion: Approximately one third of patients with symptomatic indolent lymphoma (30% with FL, 23% without FL) did not need new therapy in the long term after first-line rituximab without chemotherapy. In the entire cohort, 10-year survival was excellent with no major safety issues, which suggests that chemotherapy can be delayed safely in the majority of patients.
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| 3. |
- Adman, Per, et al.
(författare)
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171 forskare: ”Vi vuxna bör också klimatprotestera”
- 2019
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Ingår i: Dagens nyheter (DN debatt). - Stockholm. - 1101-2447.
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Tidskriftsartikel (populärvet., debatt m.m.)abstract
- DN DEBATT 26/9. Vuxna bör följa uppmaningen från ungdomarna i Fridays for future-rörelsen och protestera eftersom det politiska ledarskapet är otillräckligt. Omfattande och långvariga påtryckningar från hela samhället behövs för att få de politiskt ansvariga att utöva det ledarskap som klimatkrisen kräver, skriver 171 forskare i samhällsvetenskap och humaniora.
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| 4. |
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| 5. |
- Bhatt, Deepak L., et al.
(författare)
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Rationale, design and baseline characteristics of the effect of ticagrelor on health outcomes in diabetes mellitus patients Intervention study
- 2019
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Ingår i: Clinical Cardiology. - : Wiley. - 0160-9289 .- 1932-8737. ; 42:5, s. 498-505
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Tidskriftsartikel (refereegranskat)abstract
- In the setting of prior myocardial infarction, the oral antiplatelet ticagrelor added to aspirin reduced the risk of recurrent ischemic events, especially, in those with diabetes mellitus. Patients with stable coronary disease and diabetes are also at elevated risk and might benefit from dual antiplatelet therapy. The Effect of Ticagrelor on Health Outcomes in diabEtes Mellitus patients Intervention Study (THEMIS, NCT01991795) is a Phase 3b randomized, double-blinded, placebo-controlled trial of ticagrelor vs placebo, on top of low dose aspirin. Patients >= 50 years with type 2 diabetes receiving anti-diabetic medications for at least 6 months with stable coronary artery disease as determined by a history of previous percutaneous coronary intervention, bypass grafting, or angiographic stenosis of >= 50% of at least one coronary artery were enrolled. Patients with known prior myocardial infarction (MI) or stroke were excluded. The primary efficacy endpoint is a composite of cardiovascular death, myocardial infarction, or stroke. The primary safety endpoint is Thrombolysis in Myocardial Infarction major bleeding. A total of 19 220 patients worldwide have been randomized and at least 1385 adjudicated primary efficacy endpoint events are expected to be available for analysis, with an expected average follow-up of 40 months (maximum 58 months). Most of the exposure is on a 60 mg twice daily dose, as the dose was lowered from 90 mg twice daily partway into the study. The results may revise the boundaries of efficacy for dual antiplatelet therapy and whether it has a role outside acute coronary syndromes, prior myocardial infarction, or percutaneous coronary intervention.
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| 6. |
- Bunkenborg, Gitte, et al.
(författare)
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Bedside vital parameters that indicate early deterioration
- 2019
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Ingår i: International Journal of Health Care Quality Assurance. - 0952-6862. ; 32:1, s. 262-272
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: The purpose of this paper is to determine associations between initially recorded deviations in individual bedside vital parameters that contribute to total Modified Early Warning Score (MEWS) levels 2 or 3 and further clinical deterioration (MEWS level=4). Design/methodology/approach: This was a prospective study in which 27,504 vital parameter values, corresponding to a total MEWS level⩾2, belonging to 1,315 adult medical and surgical inpatient patients admitted to a 90-bed study setting at a university hospital, were subjected to binary logistic and COX regression analyses to determine associations between vital parameter values initially corresponding to total MEWS levels 2 or 3 and later deterioration to total MEWS level ⩾4, and to evaluate corresponding time intervals. Findings: Respiratory rate, heart rate and patient age were significantly (p=0.012, p<0.001 and p=0.028, respectively) associated with further deterioration from a total MEWS level 2, and the heart rate also (p=0.009) from a total MEWS level 3. Within 24 h from the initially recorded total MEWS levels 2 or 3, 8 and 17 percent of patients, respectively, deteriorated to a total MEWS level=4. Patients initially scoring MEWS 2 had a 27 percent 30-day mortality rate if they later scored MEWS level=4, and 8.7 percent if they did not. Practical implications: It is important to observe all patients closely, but especially elderly patients, if total MEWS levels 2 or 3 are tachypnoea and/or tachycardia related. Originality/value: Findings might contribute to patient safety by facilitating appropriate clinical and organizational decisions on adequate time spans for early warning scoring in general ward patients.
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| 8. |
- Fager Ferrari, Marcus, et al.
(författare)
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Germline heterozygous variants in genes associated with familial hemophagocytic lymphohistiocytosis as a cause of increased bleeding
- 2018
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Ingår i: Platelets. - : Informa UK Limited. - 0953-7104 .- 1369-1635. ; 29:1, s. 56-64
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Tidskriftsartikel (refereegranskat)abstract
- Familial hemophagocytic lymphohistiocytosis (FHL) is caused by biallelic variants in genes regulating granule secretion in cytotoxic lymphocytes. In FHL3–5, the affected genes UNC13D, STX11 and STXBP2 have further been shown to regulate the secretion of platelet granules, giving rise to compromised platelet function. Therefore, we aimed to investigate platelet degranulation in patients heterozygous for variants in UNC13D, STX11 and STXBP2. During the work-up of patients referred to the Coagulation Unit, Skåne University Hospital, Malmö, Sweden and the Department of Hematology, Rigshospitalet, Copenhagen, Denmark due to bleeding tendencies, 12 patients harboring heterozygous variants in UNC13D, STX11 or STXBP2 were identified using targeted whole exome sequencing. Transmission electron microscopy (TEM) was used to assess the secretion of platelet dense granules following thrombin stimulation. Platelet degranulation, activation and aggregation were further assessed by flow cytometry (FC) and light transmission aggregometry (LTA) with lumi-aggregometry. In total, eight out of twelve (67%) patients showed impaired degranulation by at least one of the assays (TEM, FC and LTA). In the 12 patients, eight different heterozygous variants were identified. One variant was strongly associated with impaired degranulation, while four of the variants were associated with impaired granule secretion to a slightly lesser extent. One additional variant was found in six out of the twelve patients, and was associated with varying degrees of degranulation impairment. Accordingly, six out of the eight (75%) identified variants were associated with impaired platelet degranulation. Our results suggest that heterozygous variants in UNC13D, STX11 and STXBP2 are sufficient to cause platelet secretion defects resulting in increased bleeding.
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| 9. |
- Jung, Christian, et al.
(författare)
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A comparison of very old patients admitted to intensive care unit after acute versus elective surgery or intervention
- 2019
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Ingår i: Journal of critical care. - : W B SAUNDERS CO-ELSEVIER INC. - 0883-9441 .- 1557-8615. ; 52, s. 141-148
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Tidskriftsartikel (refereegranskat)abstract
- Background: We aimed to evaluate differences in outcome between patients admitted to intensive care unit (ICU) after elective versus acute surgery in a multinational cohort of very old patients (80 years; VIP). Predictors of mortality, with special emphasis on frailty, were assessed.Methods: In total, 5063 VIPs were induded in this analysis, 922 were admitted after elective surgery or intervention, 4141 acutely, with 402 after acute surgery. Differences were calculated using Mann-Whitney-U test and Wilcoxon test. Univariate and multivariable logistic regression were used to assess associations with mortality.Results: Compared patients admitted after acute surgery, patients admitted after elective surgery suffered less often from frailty as defined as CFS (28% vs 46%; p < 0.001), evidenced lower SOFA scores (4 +/- 5 vs 7 +/- 7; p < 0.001). Presence of frailty (CFS >4) was associated with significantly increased mortality both in elective surgery patients (7% vs 12%; p = 0.01), in acute surgery (7% vs 12%; p = 0.02).Conclusions: VIPs admitted to ICU after elective surgery evidenced favorable outcome over patients after acute surgery even after correction for relevant confounders. Frailty might be used to guide clinicians in risk stratification in both patients admitted after elective and acute surgery.
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