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Sökning: WFRF:(Engstrøm Thomas) > (2020-2024)

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1.
  • Böhm, Felix, et al. (författare)
  • FFR-Guided Complete or Culprit-Only PCI in Patients with Myocardial Infarction
  • 2024
  • Ingår i: New England Journal of Medicine. - : Massachusetts Medical Society. - 0028-4793 .- 1533-4406. ; 390:16, s. 1481-1492
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: The benefit of fractional flow reserve (FFR)-guided complete revascularization in patients with ST-segment elevation myocardial infarction (STEMI) and multivessel coronary artery disease remains unclear. METHODS: In this multinational, registry-based, randomized trial, we assigned patients with STEMI or very-high-risk non-STEMI (NSTEMI) and multivessel disease who were undergoing primary percutaneous coronary intervention (PCI) of the culprit lesion to receive either FFR-guided complete revascularization of nonculprit lesions or no further revascularization. The primary outcome was a composite of death from any cause, myocardial infarction, or unplanned revascularization. The two key secondary outcomes were a composite of death from any cause or myocardial infarction and unplanned revascularization. RESULTS: A total of 1542 patients underwent randomization, with 764 assigned to receive FFR-guided complete revascularization and 778 assigned to receive culprit-lesion-only PCI. At a median follow-up of 4.8 years (interquartile range, 4.3 to 5.2), a primary-outcome event had occurred in 145 patients (19.0%) in the complete-revascularization group and in 159 patients (20.4%) in the culprit-lesion-only group (hazard ratio, 0.93; 95% confidence interval [CI], 0.74 to 1.17; P = 0.53). With respect to the secondary outcomes, no apparent between-group differences were observed in the composite of death from any cause or myocardial infarction (hazard ratio, 1.12; 95% CI, 0.87 to 1.44) or unplanned revascularization (hazard ratio, 0.76; 95% CI, 0.56 to 1.04). There were no apparent between-group differences in safety outcomes. CONCLUSIONS: Among patients with STEMI or very-high-risk NSTEMI and multivessel coronary artery disease, FFR-guided complete revascularization was not shown to result in a lower risk of a composite of death from any cause, myocardial infarction, or unplanned revascularization than culprit-lesion-only PCI at 4.8 years. (Funded by the Swedish Research Council and others; FULL REVASC ClinicalTrials.gov number, NCT02862119.).
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2.
  • El Farissi, Mohamed, et al. (författare)
  • A randomised trial of selective intracoronary hypothermia during primary PCI
  • 2024
  • Ingår i: EuroIntervention. - : European Society of Cardiology. - 1774-024X .- 1969-6213. ; 20:12
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: While experimental data suggest that selective intracoronary hypothermia decreases infarct size, studies in patients with ST-elevation myocardial infarction (STEMI) are lacking.AIMS: We investigated the efficacy of selective intracoronary hypothermia during primary percutaneous coronary intervention (PCI) to decrease infarct size in patients with STEMI.METHODS: In this multicentre randomised controlled trial, 200 patients with large anterior wall STEMI were randomised 1:1 to selective intracoronary hypothermia during primary PCI or primary PCI alone. Using an over-the-wire balloon catheter for infusion of cold saline and a pressure-temperature wire to monitor the intracoronary temperature, the anterior myocardium distal to the occlusion was selectively cooled to 30-33°C for 7-10 minutes before reperfusion (occlusion phase), immediately followed by 10 minutes of cooling after reperfusion (reperfusion phase). The primary endpoint was infarct size as a percentage of left ventricular mass on cardiovascular magnetic resonance imaging after 3 months.RESULTS: Selective intracoronary hypothermia was performed in 94/100 patients randomised to cooling. Distal coronary temperature decreased by 6°C within 43 seconds (interquartile range [IQR] 18-113). The median duration of the occlusion phase and reperfusion phase were 8.2 minutes (IQR 7.2-9.0) and 9.1 minutes (IQR 8.2-10.0), respectively. The infarct size at 3 months was 23.1±12.5% in the selective intracoronary hypothermia group and 21.6±12.2% in the primary PCI alone group (p=0.43). The left ventricular ejection fraction at 3 months in each group were 49.1±10.2% and 50.1±10.4%, respectively (p=0.53).CONCLUSIONS: Selective intracoronary hypothermia during primary PCI in patients with anterior wall STEMI was feasible and safe but did not decrease infarct size compared with standard primary PCI. (ClinicalTrials.gov: NCT03447834).
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3.
  • El Farissi, Mohamed, et al. (författare)
  • Safety of Selective Intracoronary Hypothermia During Primary Percutaneous Coronary Intervention in Patients With Anterior STEMI
  • 2021
  • Ingår i: JACC. - : Elsevier. - 1936-8798 .- 1876-7605. ; 14:18, s. 2047-2055
  • Tidskriftsartikel (refereegranskat)abstract
    • OBJECTIVES: The aim of this study was to determine the safety of selective intracoronary hypothermia during primary percutaneous coronary intervention (PPCI) in patients with anterior ST-segment elevation myocardial infarction (STEMI).BACKGROUND: Selective intracoronary hypothermia is a novel treatment designed to reduce myocardial reperfusion injury and is currently being investigated in the ongoing randomized controlled EURO-ICE (European Intracoronary Cooling Evaluation in Patients With ST-Elevation Myocardial Infarction) trial (NCT03447834). Data on the safety of such a procedure during PPCI are still limited.METHODS: The first 50 patients with anterior STEMI treated with selective intracoronary hypothermia during PPCI were included in this analysis and compared for safety with the first 50 patients randomized to the control group undergoing standard PPCI. In-hospital mortality, occurrence of rhythm or conduction disturbances, stent thrombosis, onset of heart failure during the procedure, and subsequent hospital admission were assessed.RESULTS: In-hospital mortality was 0%. One patient in both groups developed cardiogenic shock. Atrial fibrillation occurred in 0 and 3 patients (P = 0.24), and ventricular fibrillation occurred in 5 and 3 patients (P = 0.72) in the intracoronary hypothermia group and control group, respectively. Stent thrombosis occurred in 2 patients in the intracoronary hypothermia group; 1 instance was intraprocedural, and the other occurred following interruption of dual-antiplatelet therapy consequent to an intracranial hemorrhage 6 days after enrollment. No stent thrombosis was observed in the control group (P = 0.50).CONCLUSIONS: Selective intracoronary hypothermia during PPCI in patients with anterior STEMI can be implemented within the routine of PPCI and seems to be safe. The final safety results will be reported at the end of the trial.
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4.
  • Gaziano, Liam, et al. (författare)
  • Mild-to-moderate kidney dysfunction and cardiovascular disease : Observational and mendelian randomization analyses
  • 2022
  • Ingår i: Circulation. - : Wolters Kluwer. - 0009-7322 .- 1524-4539. ; 146:20, s. 1507-1517
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: End-stage renal disease is associated with a high risk of cardiovascular events. It is unknown, however, whether mild-to-moderate kidney dysfunction is causally related to coronary heart disease (CHD) and stroke.METHODS: Observational analyses were conducted using individual-level data from 4 population data sources (Emerging Risk Factors Collaboration, EPIC-CVD [European Prospective Investigation into Cancer and Nutrition-Cardiovascular Disease Study], Million Veteran Program, and UK Biobank), comprising 648 135 participants with no history of cardiovascular disease or diabetes at baseline, yielding 42 858 and 15 693 incident CHD and stroke events, respectively, during 6.8 million person-years of follow-up. Using a genetic risk score of 218 variants for estimated glomerular filtration rate (eGFR), we conducted Mendelian randomization analyses involving 413 718 participants (25 917 CHD and 8622 strokes) in EPIC-CVD, Million Veteran Program, and UK Biobank.RESULTS: There were U-shaped observational associations of creatinine-based eGFR with CHD and stroke, with higher risk in participants with eGFR values <60 or >105 mL·min-1·1.73 m-2, compared with those with eGFR between 60 and 105 mL·min-1·1.73 m-2. Mendelian randomization analyses for CHD showed an association among participants with eGFR <60 mL·min-1·1.73 m-2, with a 14% (95% CI, 3%-27%) higher CHD risk per 5 mL·min-1·1.73 m-2 lower genetically predicted eGFR, but not for those with eGFR >105 mL·min-1·1.73 m-2. Results were not materially different after adjustment for factors associated with the eGFR genetic risk score, such as lipoprotein(a), triglycerides, hemoglobin A1c, and blood pressure. Mendelian randomization results for stroke were nonsignificant but broadly similar to those for CHD.CONCLUSIONS: In people without manifest cardiovascular disease or diabetes, mild-to-moderate kidney dysfunction is causally related to risk of CHD, highlighting the potential value of preventive approaches that preserve and modulate kidney function.
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5.
  • Glinge, Charlotte, et al. (författare)
  • Seasonality of ventricular fibrillation at first myocardial infarction and association with viral exposure
  • 2020
  • Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 15:2
  • Tidskriftsartikel (refereegranskat)abstract
    • Aims To investigate seasonality and association of increased enterovirus and influenza activity in the community with ventricular fibrillation (VF) risk during first ST-elevation myocardial infarction (STEMI). Methods This study comprised all consecutive patients with first STEMI (n = 4,659; aged 18–80 years) admitted to the invasive catheterization laboratory between 2010–2016, at Copenhagen University Hospital, Rigshospitalet, covering eastern Denmark (2.6 million inhabitants, 45% of the Danish population). Hospital admission, prescription, and vital status data were assessed using Danish nationwide registries. We utilized monthly/weekly surveillance data for enterovirus and influenza from the Danish National Microbiology Database (2010–2016) that receives copies of laboratory tests from all Danish departments of clinical microbiology. Results Of the 4,659 consecutively enrolled STEMI patients, 581 (12%) had VF before primary percutaneous coronary intervention. In a subset (n = 807), we found that VF patients experienced more generalized fatigue and flu-like symptoms within 7 days before STEMI compared with the patients without VF (OR 3.39, 95% CI 1.76–6.54). During the study period, 2,704 individuals were diagnosed with enterovirus and 19,742 with influenza. No significant association between enterovirus and VF (OR 1.00, 95% CI 0.99–1.02), influenza and VF (OR 1.00, 95% CI 1.00–1.00), or week number and VF (p-value 0.94 for enterovirus and 0.89 for influenza) was found. Conclusion We found no clear seasonality of VF during first STEMI. Even though VF patients had experienced more generalized fatigue and flu-like symptoms within 7 days before STEMI compared with patients without VF, no relationship was found between enterovirus or influenza exposure and occurrence of VF.
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6.
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7.
  • Akhtar, Zubair, et al. (författare)
  • Optimal timing of influenza vaccination among patients with acute myocardial infarction - Findings from the IAMI trial
  • 2023
  • Ingår i: Vaccine. - : Elsevier. - 0264-410X .- 1873-2518. ; 41:48, s. 7159-7165
  • Tidskriftsartikel (refereegranskat)abstract
    • Influenza vaccination reduces the risk of adverse cardiovascular events. The IAMI trial randomly assigned 2571 patients with acute myocardial infarction (AMI) to receive influenza vaccine or saline placebo during their index hospital admission. It was conducted at 30 centers in 8 countries from October 1, 2016 to March 1, 2020. In this post-hoc exploratory sub-study, we compare the trial outcomes in patients receiving early season vaccination (n = 1188) and late season vaccination (n = 1344). The primary endpoint was the composite of all-cause death, myocardial infarction (MI), or stent thrombosis at 12 months. The cumulative incidence of the primary and key secondary endpoints by randomized treatment and early or late vaccination was estimated using the Kaplan-Meier method. In the early vaccinated group, the primary composite endpoint occurred in 36 participants (6.0%) assigned to influenza vaccine and 49 (8.4%) assigned to placebo (HR 0.69; 95% CI 0.45 to 1.07), compared to 31 participants (4.7%) assigned to influenza vaccine and 42 (6.2%) assigned to placebo (HR 0.74; 95% CI 0.47 to 1.18) in the late vaccinated group (P = 0.848 for interaction on HR scale at 1 year). We observed similar estimates for the key secondary endpoints of all-cause death and CV death. There was no statistically significant difference in vaccine effectiveness against adverse cardiovascular events by timing of vaccination. The effect of vaccination on all-cause death at one year was more pronounced in the group receiving early vaccination (HR 0.50; 95% CI, 0.29 to 0.86) compared late vaccination group (HR 0.75; 35% CI, 0.40 to 1.40) but there was no statistically significant difference between these groups (Interaction P = 0.335). In conclusion, there is insufficient evidence from the trial to establish whether there is a difference in efficacy between early and late vaccination but regardless of vaccination timing we strongly recommend influenza vaccination in all patients with cardiovascular diseases.
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8.
  • Alzuhairi, Karam Sadoon, et al. (författare)
  • Sub-acute cardiac magnetic resonance to predict irreversible reduction in left ventricular ejection fraction after ST-segment elevation myocardial infarction : A DANAMI-3 sub-study
  • 2020
  • Ingår i: International Journal of Cardiology. - : Elsevier BV. - 0167-5273. ; 301, s. 215-219
  • Tidskriftsartikel (refereegranskat)abstract
    • Aims: To predict irreversible reduction in left ventricular ejection fraction (LVEF) during admission for ST-segment elevation myocardial infarction (STEMI) using cardiac magnetic resonance (CMR) in addition to classical clinical parameters. Irreversible reduction in LVEF is an important prognostic factor after STEMI which necessitates medical therapy and implantation of prophylactic implantable cardioverter defibrillator (ICD). Methods and results: A post-hoc analysis of DANAMI-3 trial program (Third DANish Study of Optimal Acute Treatment of Patients With ST-elevation Myocardial Infarction) which recruited 649 patients who had CMR performed during index hospitalization and after 3 months. Patients were divided into two groups according to CMR-LVEF at 3 months: Group 1 with LVEF≤35% and Group 2 with LVEF>35%. Group 1 included 15 patients (2.3%) while Group 2 included 634 patients (97.7%). A multivariate analysis showed that: Killip class >1 (OR 7.39; CI:1.47–36.21, P = 0.01), symptom onset-to-wire ≥6 h (OR 7.19; CI 1.07–50.91, P = 0.04), LVEF≤35% using index echocardiography (OR 7.11; CI: 1.27–47.43, P = 0.03), and infarct size ≥40% of LV on index CMR (OR 42.62; CI:7.83–328.29, P < 0.001) independently correlated with a final LVEF≤35%. Clinical models consisted of these parameters could identify 7 out of 15 patients in Group 1 with 100% positive predictive value. Conclusion: Together with other clinical measurements, the assessment of infarct size using late Gadolinium enhancement by CMR during hospitalization is a strong predictor of irreversible reduction in CMR_LVEF ≤35. That could potentially, after validation with future research, aids the selection and treatment of high-risk patients after STEMI, including implantation of prophylactic ICD during index hospitalization.
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9.
  • Andersson, Thomas K., et al. (författare)
  • Perceptions of Experiences of Recovery After Pancreaticoduodenectomy-A Phenomenographic Interview Study
  • 2022
  • Ingår i: Cancer Nursing. - : Ovid Technologies (Wolters Kluwer Health). - 0162-220X .- 1538-9804. ; 45:3, s. 172-180
  • Tidskriftsartikel (refereegranskat)abstract
    • Background Pancreatic surgery in the context of enhanced recovery has mainly been evaluated using clinical variables. However, there is limited knowledge about patients' perceptions of recovery in this context. Hence, the aim of this study was to explore patients' perceptions of recovery after pancreatic surgery within an enhanced recovery program. Objective To explore the variations in patients' perceptions, a qualitatively designed study was undertaken. Methods Data in this phenomenographic study consisted of interviews with 19 patients at 4 to 6 weeks after surgery. Results Recovery after pancreatic surgery was classified into 5 categories, based on patients' perceptions: to be as before, affected by symptoms, physical activity, understanding the process, and facilitated by other people. Conclusion The study focused on various areas of recovery, which took place between the in-hospital and after-discharge phases. Physical experiences were found to disturb recovery, in contrast to social and emotional experiences, which facilitated recovery. Variations in perceptions of recovery suggest that care may need to be more individualized, both in the preoperative and the postoperative phase. Working with realistic expectations and early patient education might better prepare patients to continue working on their own recovery after discharge from the hospital. Implications for Practice Major cancer surgery needs to be perceived as a personal journey for the patient, even in enhanced recovery program care. Preoperative education is good, but adding continuous and individually adopted education during recovery is better. Knowledge about both hindering and facilitating factors for recovery is important for the healthcare personal.
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10.
  • Barregård, Lars, 1948, et al. (författare)
  • Cadmium Exposure and Coronary Artery Atherosclerosis: A Cross-Sectional Population-Based Study of Swedish Middle-Aged Adults
  • 2021
  • Ingår i: Environmental health perspectives. - 1552-9924 .- 0091-6765. ; 129:6
  • Tidskriftsartikel (refereegranskat)abstract
    • The general population is ubiquitously exposed to the toxic metal cadmium through the diet and smoking. Cadmium exposure is associated with increased morbidity and mortality in myocardial infarction and stroke. Atherosclerosis is the main underlying mechanism of myocardial infarction. However, associations between cadmium and coronary artery atherosclerosis have not been examined.Our study sought to examine the hypothesis that blood cadmium (B-Cd) is positively associated with coronary artery calcification, as a measure of coronary artery atherosclerosis in the population-based Swedish SCAPIS study.Our analysis included 5,627 individuals (51% women), age 50-64 y, enrolled from 2013 to 2018. The coronary artery calcium score (CACS) was obtained from computed tomography. Blood cadmium was determined by inductively coupled plasma mass spectrometry (ICP-MS). Associations between B-Cd and coronary artery calcium score (CACS Agatston score) were evaluated using prevalence ratios (PRs) in models adjusted for sex, age, smoking, hypertension, diabetes, low-density cholesterol/high-density cholesterol ratio, and family history.The median B-Cd concentration was 0.24 μ g / L . The prevalence of positive coronary artery calcium ( CACS > 0 ) was 41% and the prevalence of CACS ≥ 100 was 13%. Relative to the lowest quartile (Q) of B-Cd ( < 0.16 μ g / L ), the highest quartile (median 0.63 μ g / L ) was associated with a small but significant increase in CACS > 0 (PR 1.1; 95% CI: 1.0, 1.3), and a greater relative increase in CACS ≥ 100 (PR 1.6; 95% CI: 1.3, 2.0). When restricted to 2,446 never-smokers, corresponding PRs were 1.1 (95% CI 0.9, 1.3) for CACS > 0 (63 cases in Q4) and 1.7 (95% CI 1.1, 2.7) for CACS ≥ 100 (17 cases in Q4).Blood cadmium in the highest quartile was associated with CACS in a general population sample with low to moderate cadmium exposure. This supports the hypothesis that atherosclerosis is an important mechanism underlying the associations between cadmium and incident cardiovascular disease. The findings suggest that public health measures to reduce cadmium exposure are warranted. https://doi.org/10.1289/EHP8523.
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11.
  • Baykal, Yunus, et al. (författare)
  • Detrital zircon U–Pb age analysis of last glacial loess sources and proglacial sediment dynamics in the Northern European Plain
  • 2021
  • Ingår i: Quaternary Science Reviews. - : Elsevier. - 0277-3791 .- 1873-457X. ; 274
  • Tidskriftsartikel (refereegranskat)abstract
    • Loess deposits along the northern fringe of the European loess belt potentially record past changes in dust emission from areas proximal to former ice sheets. Recent chronologies from loess deposits across this region generally agree on greatly enhanced dust deposition rates when the Fennoscandian Ice Sheet reached its maximum extent during the late last glacial. However, uncertainties over the material's source and origin limit understanding of the causes of this enhanced dust activity. In particular, loess in southwestern Poland has been attributed to multiple origins, mainly involving glaciofluvial outwash plains along the Fennoscandian Ice Sheet margin and/or local sources in the mountainous areas of the Sudetes and Western Carpathians. Here we apply detrital zircon U–Pb age analyses for a large number of grains recovered from four loess samples taken from different stratigraphic units exposed at Biały Kościół in southwestern Poland, previously luminescence dated to MIS 4–2, to assess loess provenance as well as its temporal evolution during last glacial Fennoscandian Ice Sheet fluctuations. Furthermore, we analysed the detrital zircon U–Pb age spectra of five samples from potential source sediments to constrain the history of sediment recycling and mixing within the Northern European Plain prior to deflation and loess deposition. The broad range of zircon age components detected in the four loess samples suggests both Fennoscandian and closer Peri-Gondwanan proto-sources while a narrow, dominant Carboniferous age peak is consistent with sourcing from the local Strzelin Hills in the Sudetic foreland. However, the presence of both Fennoscandian and Peri-Gondwanan derived grains in samples from potential source sediments reveals that this mixture of sediment sources is widespread across the Northern European Plain, as a result of long-term glacial and fluvial reworking of cover sediments in the proglacial area throughout the Quaternary. Local rivers draining the Sudetic foreland transported this Fennoscandian-Peri-Gondwanan sediment mixture along with particles denuded from the Strzelin Hills, resulting in a nearby, temporally stable dust source for the Biały Kościół loess during MIS 4–2, while dust emission rates were substantially increased during the last glacial maximum. Given that our model for loess formation at Biały Kościół essentially involves sediment distribution via rivers prior to short distance aeolian transport, we infer that the proportion of northern ice sheet derived particles in European loess deposits is mainly controlled by the drainage pattern of major rivers in relation to Pleistocene ice margins where glaciofluvial sediment is abundant. Based on the presence of Fennoscandian derived zircon grains in European loess deposits, we constrain a southern limit of the influence of northern ice sheet dust sources along the central European highlands that currently divide drainage between the Northern European Plain and the Danube Basins.
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12.
  • El Farissi, Mohamed, et al. (författare)
  • Selective intracoronary hypothermia in patients with ST-elevation myocardial infarction : Rationale and design of the EURO-ICE trial
  • 2021
  • Ingår i: EuroIntervention. - : European Society of Cardiology. - 1774-024X .- 1969-6213. ; 16:17, s. 1444-1446
  • Tidskriftsartikel (refereegranskat)abstract
    • In ST-elevation myocardial infarction (STEMI), early restoration of blood flow, preferably by primary percutaneous coronary intervention (PPCI), is paramount to limit infarct size (IS) and improve long-term outcomes. However, reperfusion by itself may also cause damage to the myocardium and increase IS. This has been termed myocardial reperfusion injury. In animal models of acute myocardial infarction, it has been demonstrated that hypothermia decreases IS. In contrast, human studies applying systemic cooling methods have not yet been able to confirm this protective effect.Recently, we developed a new method to provide selective intracoronary hypothermia during PPCI. The EUROpean Intracoronary Cooling Evaluation in patients with ST-elevation myocardial infarction (EURO-ICE) trial will assess the efficacy of this method.
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13.
  • Engström, Maria, et al. (författare)
  • Child Health Nurses' experiences of addressing psychosocial risk factors with the families they meet
  • 2021
  • Ingår i: Acta Paediatrica. - : John Wiley & Sons. - 0803-5253 .- 1651-2227. ; 110:2, s. 574-583
  • Tidskriftsartikel (refereegranskat)abstract
    • Aim To examine how child health nurses perceive the routine assessment of psychosocial risk factors in the family environment as well as their self-reported competence and the present organisational conditions in this context. Method A mixed-methods design was used, including three focus group interviews and a web-based survey. Qualitative data were analysed using systematic text condensation. Quantitative data were analysed at the descriptive level. Results Nurses expressed that identifying psychosocial risk factors was both important and relevant to their work. They had little formal training and education on most psychosocial risk factors, and they lacked structured methods to address them. In areas where nurses reported more formal education and a structured methodology (depression, parental stress), they rated to a higher degree that they possessed sufficient skills and sense of security. The nurses perceived that they seldom came into contact with families with financial problems, hazardous alcohol use or intimate partner violence. Conclusions There is a gap between the nurses' attitudes regarding the importance of helping families in need and their ability to do so with the current level of training and methodological support. The results suggest that, in many cases, psychosocial problems remain undetected.
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14.
  • Engström-Ruud, Linda, et al. (författare)
  • Activation of GFRAL+ neurons induces hypothermia and glucoregulatory responses associated with nausea and torpor.
  • 2024
  • Ingår i: Cell reports. - 2211-1247. ; 43:4
  • Tidskriftsartikel (refereegranskat)abstract
    • GFRAL-expressing neurons actuate aversion and nausea, are targets for obesity treatment, and may mediate metformin effects by long-term GDF15-GFRAL agonism. Whether GFRAL+ neurons acutely regulate glucose and energy homeostasis is, however, underexplored. Here, we report that cell-specific activation of GFRAL+ neurons using a variety of techniques causes a torpor-like state, including hypothermia, the release of stress hormones, a shift from glucose to lipid oxidation, and impaired insulin sensitivity, glucose tolerance, and skeletal muscle glucose uptake but augmented glucose uptake in visceral fat. Metabolomic analysis of blood and transcriptomics of muscle and fat indicate alterations in ketogenesis, insulin signaling, adipose tissue differentiation and mitogenesis, and energy fluxes. Our findings indicate that acute GFRAL+ neuron activation induces endocrine and gluco- and thermoregulatory responses associated with nausea and torpor. While chronic activation of GFRAL signaling promotes weight loss in obesity, these results show that acute activation of GFRAL+ neurons causes hypothermia and hyperglycemia.
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15.
  • Erlinge, David, et al. (författare)
  • Identification of vulnerable plaques and patients by intracoronary near-infrared spectroscopy and ultrasound (PROSPECT II) : a prospective natural history study
  • 2021
  • Ingår i: The Lancet. - : Elsevier. - 0140-6736 .- 1474-547X. ; 397:10278, s. 985-995
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Near-infrared spectroscopy (NIRS) and intravascular ultrasound are promising imaging modalities to identify non-obstructive plaques likely to cause coronary-related events. We aimed to assess whether combined NIRS and intravascular ultrasound can identify high-risk plaques and patients that are at risk for future major adverse cardiac events (MACEs).Methods: PROSPECT II is an investigator-sponsored, multicentre, prospective natural history study done at 14 university hospitals and two community hospitals in Denmark, Norway, and Sweden. We recruited patients of any age with recent (within past 4 weeks) myocardial infarction. After treatment of all flow-limiting coronary lesions, three-vessel imaging was done with a combined NIRS and intravascular ultrasound catheter. Untreated lesions (also known as non-culprit lesions) were identified by intravascular ultrasound and their lipid content was assessed by NIRS. The primary outcome was the covariate-adjusted rate of MACEs (the composite of cardiac death, myocardial infarction, unstable angina, or progressive angina) arising from untreated non-culprit lesions during follow-up. The relations between plaques with high lipid content, large plaque burden, and small lumen areas and patient-level and lesion-level events were determined. This trial is registered with ClinicalTrials.gov, NCT02171065.Findings: Between June 10, 2014, and Dec 20, 2017, 3629 non-culprit lesions were characterised in 898 patients (153 [17%] women, 745 [83%] men; median age 63 [IQR 55-70] years). Median follow-up was 3.7 (IQR 3.0-4.4) years. Adverse events within 4 years occurred in 112 (13.2%, 95% CI 11.0-15.6) of 898 patients, with 66 (8.0%, 95% CI 6.2-10.0) arising from 78 untreated non-culprit lesions (mean baseline angiographic diameter stenosis 46.9% [SD 15.9]). Highly lipidic lesions (851 [24%] of 3500 lesions, present in 520 [59%] of 884 patients) were an independent predictor of patient-level non-culprit lesion-related MACEs (adjusted odds ratio 2.27, 95% CI 1.25-4.13) and nonculprit lesion-specific MACEs (7.83, 4.12-14.89). Large plaque burden (787 [22%] of 3629 lesions, present in 530 [59%] of 898 patients) was also an independent predictor of non-culprit lesion-related MACEs. Lesions with both large plaque burden by intravascular ultrasound and large lipid-rich cores by NIRS had a 4-year non-culprit lesion-related MACE rate of 7.0% (95% CI 4.0-10.0). Patients in whom one or more such lesions were identified had a 4-year non-culprit lesion-related MACE rate of 13.2% (95% CI 9.4-17.6).Interpretation: Combined NIRS and intravascular ultrasound detects angiographically non-obstructive lesions with a high lipid content and large plaque burden that are at increased risk for future adverse cardiac outcomes.
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16.
  • Folkersen, Lasse, et al. (författare)
  • Genomic and drug target evaluation of 90 cardiovascular proteins in 30,931 individuals.
  • 2020
  • Ingår i: Nature metabolism. - : Springer Science and Business Media LLC. - 2522-5812. ; 2:10, s. 1135-1148
  • Tidskriftsartikel (refereegranskat)abstract
    • Circulating proteins are vital in human health and disease and are frequently used as biomarkers for clinical decision-making or as targets for pharmacological intervention. Here, we map and replicate protein quantitative trait loci (pQTL) for 90 cardiovascular proteins in over 30,000 individuals, resulting in 451 pQTLs for 85 proteins. For each protein, we further perform pathway mapping to obtain trans-pQTL gene and regulatory designations. We substantiate these regulatory findings with orthogonal evidence for trans-pQTLs using mouse knockdown experiments (ABCA1 and TRIB1) and clinical trial results (chemokine receptors CCR2 and CCR5), with consistent regulation. Finally, we evaluate known drug targets, and suggest new target candidates or repositioning opportunities using Mendelian randomization. This identifies 11 proteins with causal evidence of involvement in human disease that have not previously been targeted, including EGF, IL-16, PAPPA, SPON1, F3, ADM, CASP-8, CHI3L1, CXCL16, GDF15 and MMP-12. Taken together, these findings demonstrate the utility of large-scale mapping of the genetics of the proteome and provide a resource for future precision studies of circulating proteins in human health.
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17.
  • Fröbert, Ole, 1964-, et al. (författare)
  • Clinical Impact of Influenza Vaccination after ST- and Non-ST-segment elevation Myocardial Infarction Insights from the IAMI trial
  • 2023
  • Ingår i: American Heart Journal. - : Elsevier. - 0002-8703 .- 1097-6744. ; 255, s. 82-89
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Influenza vaccination early after myocardial infarction (MI) improves prognosis but vaccine effectiveness may differ dependent on type of MI.METHODS: A total of 2571 participants were prospectively enrolled in the IAMI trial and randomly assigned to receive in-hospital inactivated influenza vaccine or saline placebo. The trial was conducted at 30 centers in 8 countries from October 1, 2016 to March 1, 2020. Here we report vaccine effectiveness in the 2467 participants with ST-segment elevation MI (STEMI, n=1348) or non-ST-segment elevation MI (NSTEMI, n=1119). The primary endpoint was the composite of all-cause death, MI, or stent thrombosis at 12 months. Cumulative incidence of the primary and key secondary endpoints by randomized treatment and NSTEMI/STEMI was estimated using the Kaplan-Meier method. Treatment effects were evaluated with formal interaction testing to assess for effect modification.RESULTS: Baseline risk was higher in participants with NSTEMI. In the NSTEMI group the primary endpoint occurred in 6.5% of participants assigned to influenza vaccine and 10.5% assigned to placebo (hazard ratio [HR], 0.60; 95% CI, 0.39-0.91), compared to 4.1% assigned to influenza vaccine and 4.5% assigned to placebo in the STEMI group (HR, 0.90; 95% CI, 0.54-1.50, P=0.237 for interaction). Similar findings were seen for the key secondary endpoints of all-cause death and cardiovascular death. The Kaplan-Meier risk difference in all-cause death at 1 year was more pronounced in participants with NSTEMI (NSTEMI: HR, 0.47; 95% CI 0.28-0.80, STEMI: HR, 0.86; 95% CI, 0.43-1.70, interaction P=0.028).CONCLUSIONS: The beneficial effect of influenza vaccination on adverse cardiovascular events may be enhanced in patients with NSTEMI compared to those with STEMI.
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18.
  • Fröbert, Ole, 1964-, et al. (författare)
  • Influenza Vaccination after Myocardial Infarction : A Randomized, Double-Blind, Placebo-Controlled, Multicenter Trial
  • 2021
  • Ingår i: Circulation. - : Lippincott Williams & Wilkins. - 0009-7322 .- 1524-4539. ; 144:18, s. 1476-1484
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Observational and small randomized studies suggest that influenza vaccine may reduce future cardiovascular events in patients with cardiovascular disease.Methods: We conducted an investigator-initiated, randomized, double-blind trial to compare inactivated influenza vaccine with saline placebo administered shortly after myocardial infarction (MI) (99.7% of patients) or high-risk stable coronary heart disease (0.3%). The primary endpoint was the composite of all-cause death, MI, or stent thrombosis at 12 months. A hierarchical testing strategy was used for the key secondary endpoints: all-cause death, cardiovascular death, MI, and stent thrombosis.Results: Due to the Covid-19 pandemic, the data safety and monitoring board decided to halt the trial before attaining the prespecified sample size. Between October 1, 2016, and March 1, 2020, 2571 participants were randomized at 30 centers across eight countries; 1290 assigned to influenza vaccine and 1281 to placebo. Over the 12-month follow-up, the primary outcome occurred in 67 participants (5.3%) assigned influenza vaccine and 91 participants (7.2%) assigned placebo (hazard ratio, 0.72; 95% confidence interval, 0.52 to 0.99; P=0.040). Rates of all-cause death were 2.9% and 4.9% (hazard ratio, 0.59; 0.39 to 0.89; P=0.010), of cardiovascular death 2.7% and 4.5%, (hazard ratio, 0.59; 0.39 to 0.90; P=0.014), and of MI 2.0% and 2.4% (hazard ratio, 0.86; 0.50 to 1.46, P=0.57) in the influenza vaccine and placebo groups, respectively. Conclusions: Influenza vaccination early after an MI or in high-risk coronary heart disease resulted in a lower risk of a composite of all-cause death, MI, or stent thrombosis, as well as a lower risk of all-cause death and cardiovascular death at 12 months compared with placebo.Clinical Trial Registration: URL: http://www.clinicaltrials.gov Unique identifier: NCT02831608.
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19.
  • Gauffin, Helena, et al. (författare)
  • Similar Profile and Magnitude of Cognitive Impairments in Focal and Generalized Epilepsy : A Pilot Study
  • 2022
  • Ingår i: Frontiers in Neurology. - Lausanne, Switzerland : Frontiers Media S.A.. - 1664-2295. ; 12
  • Tidskriftsartikel (refereegranskat)abstract
    • Introduction: Cognitive impairments in epilepsy are not well-understood. In addition, long-term emotional, interpersonal, and social consequences of the underlying disturbances are important to evaluate.Purpose: To compare cognitive function including language in young adults with focal or generalized epilepsy. In addition, quality of life and self-esteem were investigated.Patients and Methods: Young adults with no primary intellectual disability, 17 with focal epilepsy and 11 with generalized epilepsy participated and were compared to 28 healthy controls. Groups were matched on age (mean = 26 years), sex, and education. Participants were administered a battery of neuropsychological tasks and carried out self-ratings of quality of life, self-esteem, and psychological problems.Results: Similar impairments regarding cognitive function were noted in focal and generalized epilepsy. The cognitive domains tested were episodic long-term memory, executive functions, attention, working memory, visuospatial functions, and language. Both epilepsy groups had lower results compared to controls (effect sizes 0.24-1.07). The total number of convulsive seizures was predictive of episodic long-term memory function. Participants with focal epilepsy reported lower quality of life than participants with generalized epilepsy. Lowered self-esteem values were seen in both epilepsy groups and particularly in those with focal epilepsy. Along with measures of cognitive speed and depression, the total number of seizures explained more than 50% of variation in quality of life.Conclusion: Interestingly, similarities rather than differences characterized the widespread cognitive deficits that were seen in focal and generalized epilepsy, ranging from mild to moderate. These similarities were modified by quality of life and self-esteem. This study confirms the notion that epilepsy is a network disorder.
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20.
  • Georgiopoulos, Charalampos, et al. (författare)
  • Differential connectivity of the posterior piriform cortex in Parkinson’s disease and postviral olfactory dysfunction : an fMRI study
  • 2024
  • Ingår i: Scientific Reports. - : NATURE PORTFOLIO. - 2045-2322. ; 14:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Olfactory dysfunction is a common feature of both postviral upper respiratory tract infections (PV) and idiopathic Parkinson’s disease (PD). Our aim was to investigate potential differences in the connectivity of the posterior piriform cortex, a major component of the olfactory cortex, between PV and PD patients. Fifteen healthy controls (median age 66 years, 9 men), 15 PV (median age 63 years, 7 men) and 14 PD patients (median age 70 years, 9 men) were examined with task-based olfactory fMRI, including two odors: peach and fish. fMRI data were analyzed with the co-activation pattern (CAP) toolbox, which allows a dynamic temporal assessment of posterior piriform cortex (PPC) connectivity. CAP analysis revealed 2 distinct brain networks interacting with the PPC. The first network included regions related to emotion recognition and attention, such as the anterior cingulate and the middle frontal gyri. The occurrences of this network were significantly fewer in PD patients compared to healthy controls (p = 0.023), with no significant differences among PV patients and the other groups. The second network revealed a dissociation between the olfactory cortex (piriform and entorhinal cortices), the anterior cingulate gyrus and the middle frontal gyri. This second network was significantly more active during the latter part of the stimulation, across all groups, possibly due to habituation. Our study shows how the PPC interacts with areas that regulate higher order processing and how this network is substantially affected in PD. Our findings also suggest that olfactory habituation is independent of disease.
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21.
  • Giassi, Marianna, et al. (författare)
  • Capturing the experimental behaviour of a point-absorber WEC by simplified numerical models
  • 2020
  • Ingår i: Journal of Fluids and Structures. - : Elsevier BV. - 0889-9746 .- 1095-8622. ; 99
  • Tidskriftsartikel (refereegranskat)abstract
    • The paper presents a wave basin experiment of a direct-driven point-absorber wave energy converter moving in six degrees of freedom. The goal of the work is to study the dynamics and energy absorption of the wave energy converter, and to verify under which conditions numerical models restricted to heave can capture the behaviour of a point-absorber moving in six degrees of freedom. Several regular and irregular long-crested waves and different damping values of the power take-off system have been tested. We collected data in terms of power output, device motion in six degrees of freedom and wave elevation at different points of the wave basin. A single-body numerical model in the frequency domain and a two-body model in the time domain are used in the study. Motion instabilities due to parametric resonance observed during the experiments are discussed and analysis of the buoy motion in terms of the Mathieu instability is also presented. Our results show that the simplified models can reproduce the body dynamics of the studied converter as long as the transverse non-linear instabilities are not excited, which typically is the case in irregular waves. The performance of the more complex time domain model is able to reproduce both the buoy and PTO dynamics, while the simpler frequency domain model can only reproduce the PTO dynamics for specific cases. Finally, we show that the two-body dynamics of the studied wave energy converter affects the power absorption significantly, and that common assumptions in the numerical models, such as stiff mooring line or that the float moves only in heave, may lead to incorrect predictions for certain sea states.
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22.
  • Glinge, Charlotte, et al. (författare)
  • Sibling history is associated with heart failure after a first myocardial infarction
  • 2020
  • Ingår i: Open Heart. - : BMJ. - 2398-595X .- 2053-3624. ; 7:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective: Morbidity and mortality due to heart failure (HF) as a complication of myocardial infarction (MI) is high, and remains among the leading causes of death and hospitalisation. This study investigated the association between family history of MI with or without HF, and the risk of developing HF after first MI. Methods: Through nationwide registries, we identified all individuals aged 18-50 years hospitalised with first MI from 1997 to 2016 in Denmark. We identified 13 810 patients with MI, and the cohort was followed until HF diagnosis, second MI, 3 years after index MI, emigration, death or the end of 2016, whichever occurred first. HRs were estimated by Cox hazard regression models adjusted for sex, age, calendar year and comorbidities (reference: patients with no family history of MI). Results: After adjustment, we observed an increased risk of MI-induced HF for those having a sibling with MI with HF (HR 2.05, 95% CI 1.02 to 4.12). Those having a sibling with MI without HF also had a significant, but lower increased risk of HF (HR 1.39, 95% CI 1.05 to 1.84). Parental history of MI with or without HF was not associated with HF. Conclusion: In this nationwide cohort, sibling history of MI with or without HF was associated with increased risk of HF after first MI, while a parental family history was not, suggesting that shared environmental factors may predominate in the determination of risk for developing HF.
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23.
  • Guldbrand, Carl, 1997, et al. (författare)
  • Low-level exposure to lead and atherosclerosis in the carotid arteries : Results from the Swedish population-based cohort SCAPIS
  • 2024
  • Ingår i: Environmental Research. - 0013-9351 .- 1096-0953. ; 244
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Lead exposure is associated with cardiovascular disease. Atherosclerosis has been hypothesized to be one of the underlying mechanisms behind this association. Aim: To investigate whether lead exposure is associated with an increased risk of atherosclerosis in the carotid arteries in a large Swedish population-based cohort. Methods: We performed a cross-sectional study using data from the population-based Swedish CardioPulmonary bioImage Study (SCAPIS), including 5622 middle-aged men and women, enrolled 2013–2018. Blood lead (B–Pb), measured by inductively coupled plasma mass spectrometry, was used as exposure biomarker. The presence of atherosclerotic plaque in the carotid arteries (yes/no), total plaque area (mm2) and the presence of large plaques (>25 mm2) were determined by ultrasonography. Associations between B–Pb and the different outcomes were analysed using Poisson and linear regression models, adjusted for potential confounders. Results: Atherosclerotic plaque was present in 57% of the individuals, for whom the median total plaque area was 16 mm2 (range: 0.2–222). The median B–Pb concentration was 14 μg/L (range: 0.75–203). After adjusting for potential confounders, individuals in the fourth quartile of B–Pb (Q4) had a prevalence ratio (PR) for plaque of 1.08 (95% CI: 1.01, 1.16) when compared with the first quartile (Q1). A 10 μg/L increase in B–Pb concentrations was associated with an increase of 0.92 mm2 (95% CI: 0.14, 1.71) in total plaque area. The PR for large plaque was 1.09 (95% CI: 0.84, 1.42 for Q4 vs Q1). Conclusions: This study shows an association between B–Pb and atherosclerosis in the carotid arteries providing some support for the hypothesis that atherosclerosis is one of the mechanisms underlying the association between lead exposure and cardiovascular disease.
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24.
  • Gyldenkerne, Christine, et al. (författare)
  • Coronary Artery Lesion Lipid Content and Plaque Burden in Diabetic and Nondiabetic Patients : PROSPECT II
  • 2023
  • Ingår i: Circulation. - : Lippincott Williams & Wilkins. - 0009-7322 .- 1524-4539. ; 147:6, s. 469-481
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Patients with diabetes have increased rates of major adverse cardiac events (MACEs). We hypothesized that this is explained by diabetes-associated differences in coronary plaque morphology and lipid content.METHODS: In PROSPECT II (Providing Regional Observations to Study Predictors of Events in the Coronary Tree), 898 patients with acute myocardial infarction with or without ST-segment elevation underwent 3-vessel quantitative coronary angiography and coregistered near-infrared spectroscopy and intravascular ultrasound imaging after successful percutaneous coronary intervention. Subsequent MACEs were adjudicated to either treated culprit lesions or untreated nonculprit lesions. This substudy stratified patients by diabetes status and assessed baseline culprit and nonculprit prevalence of high-risk plaque characteristics defined as maximum plaque burden ≥70% and maximum lipid core burden index ≥324.7. Separate covariate-adjusted multivariable models were performed to identify whether diabetes was associated with nonculprit lesion-related MACEs and high-risk plaque characteristics.RESULTS: Diabetes was present in 109 of 898 patients (12.1%). During a median 3.7-year follow-up, MACEs occurred more frequently in patients with versus without diabetes (20.1% versus 13.5% [odds ratio (OR), 1.94 (95% CI, 1.14-3.30)]), primarily attributable to increased risk of myocardial infarction related to culprit lesion restenosis (4.3% versus 1.1% [OR, 3.78 (95% CI, 1.12-12.77)]) and nonculprit lesion-related spontaneous myocardial infarction (9.3% versus 3.8% [OR, 2.74 (95% CI, 1.25-6.04)]). However, baseline prevalence of high-risk plaque characteristics was similar for patients with versus without diabetes concerning culprit (maximum plaque burden ≥70%: 90% versus 93%, P=0.34; maximum lipid core burden index ≥324.7: 66% versus 70%, P=0.49) and nonculprit lesions (maximum plaque burden ≥70%: 23% versus 22%, P=0.37; maximum lipid core burden index ≥324.7: 26% versus 24%, P=0.47). In multivariable models, diabetes was associated with MACEs in nonculprit lesions (adjusted OR, 2.47 [95% CI, 1.21-5.04]) but not with prevalence of high-risk plaque characteristics (adjusted OR, 1.21 [95% CI, 0.86-1.69]).CONCLUSIONS: Among patients with recent myocardial infarction, both treated and untreated lesions contributed to the diabetes-associated ≈2-fold increased MACE rate during the 3.7-year follow-up. Diabetes-related plaque characteristics that might underlie this increased risk were not identified by multimodality imaging.
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25.
  • Jacobsen, Mia Ravn, et al. (författare)
  • Clopidogrel, prasugrel, and ticagrelor for all-comers with ST-segment elevation myocardial infarction
  • 2021
  • Ingår i: International Journal of Cardiology. - : Elsevier BV. - 0167-5273. ; 342, s. 15-22
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: To compare effectiveness and safety of clopidogrel, prasugrel, and ticagrelor among all-comers with ST-segment elevation myocardial infarction (STEMI) and extend the knowledge from randomized clinical trials. Methods: All consecutive patients with STEMI admitted to Copenhagen University Hospital, Rigshospitalet, from 2009 to 2016 were identified via the Eastern Danish Heart Registry. By individual linkage to Danish nationwide registries, claimed drugs and end points were obtained. Patients alive a week post-discharge were included, stratified according to clopidogrel, prasugrel, or ticagrelor treatment, and followed for a year. The effectiveness end point (a composite of all-cause mortality, recurrent myocardial infarction, and ischemic stroke) and safety end point (a composite of bleedings leading to hospitalization) were assessed by multivariate Cox proportional-hazards models. Results: In total, 5123 patients were included (clopidogrel [1245], prasugrel [1902], ticagrelor [1976]) with ≥95% treatment persistency. Concomitant use of aspirin was ≥95%. Females accounted for 24% and elderly for 17%. Compared with clopidogrel, the effectiveness end point occurred less often for ticagrelor (HR 0.50, 95% CI 0.35–0.70) and prasugrel (HR 0.48, 95% CI 0.33–0.68) without differences in bleedings leading to hospitalization. No differences in comparative effectiveness or safety were found between prasugrel and ticagrelor. Sensitivity analyses with time-dependent drug exposure and the period 2011–2015 showed similar results. Conclusions: Among all-comers with STEMI, ticagrelor and prasugrel were associated with reduced incidence of the composite end point of all-cause mortality, recurrent myocardial infarction, and ischemic stroke without an increase in bleedings leading to hospitalization compared with clopidogrel. No differences were found between prasugrel and ticagrelor.
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26.
  • Kornfält Isberg, Helena, et al. (författare)
  • Different antibiotic regimes in men diagnosed with lower urinary tract infection - a retrospective register-based study
  • 2020
  • Ingår i: Scandinavian Journal of Primary Health Care. - : Informa UK Limited. - 0281-3432 .- 1502-7724. ; 38:3, s. 291-299
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective To compare the proportion of therapy failure, recurrence and complications within 30 days after consultation between men diagnosed with lower urinary tract infection (UTI) treated with narrow-spectrum antibiotics (nitrofurantoin or pivmecillinam) and broad-spectrum antibiotics (fluoroquinolones or trimethoprim or trimethoprim/sulfamethoxazole). Design A retrospective cohort study based on data derived from electronic medical records between January 2012 and December 2015. Setting Primary health care and hospital care in five different counties in Sweden. Patients:A total of 16,555 men aged between 18 and 79 years diagnosed with lower UTI. Main outcome measures Treatment with narrow-spectrum antibiotics was compared with broad-spectrum antibiotics regarding therapy failure, recurrence and complications within 30 days. Results The median age of included men was 65 IQR (51-72) years. Narrow-spectrum antibiotics were prescribed in 8457 (40%) and broad-spectrum antibiotics in 12,667 (60%) cases, respectively. Therapy failure was registered in 192 (0.9%), recurrence in 1277 (6%) and complications in 121 (0.6%) cases. Therapy failure and recurrence were more common in patients treated with narrow-spectrum antibiotics and trimethoprim (p < 0.001), but no such difference could be detected regarding complications. Conclusion There was no difference in incidence of complications within 30 days between men treated with narrow- or broad-spectrum antibiotics. Patients prescribed broad-spectrum antibiotics had lower odds of reconsultation because of therapy failure and recurrence. From current data, treatment with narrow-spectrum antibiotics seems to be an optimal choice regarding preventing complications when treating men with lower UTI.
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27.
  • Kumsars, Indulis, et al. (författare)
  • Randomised comparison of provisional side branch stenting versus a two-stent strategy for treatment of true coronary bifurcation lesions involving a large side branch : the Nordic-Baltic Bifurcation Study IV
  • 2020
  • Ingår i: Open heart. - : BMJ Publishing Group Ltd. - 2053-3624. ; 7:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: It is still uncertain whether coronary bifurcations with lesions involving a large side branch (SB) should be treated by stenting the main vessel and provisional stenting of the SB (simple) or by routine two-stent techniques (complex). We aimed to compare clinical outcome after treatment of lesions in large bifurcations by simple or complex stent implantation.Methods: The study was a randomised, superiority trial. Enrolment required a SB >= 2.75 mm, >= 50% diameter stenosis in both vessels, and allowed SB lesion length up to 15 mm. The primary endpoint was a composite of cardiac death, non-procedural myocardial infarction and target lesion revascularisation at 6 months. Two-year clinical follow-up was included in this primary reporting due to lower than expected event rates.Results: A total of 450 patients were assigned to simple stenting (n = 221) or complex stenting (n=229) in 14 Nordic and Baltic centres. Two-year follow-up was available in 218 (98.6%) and 228 (99.5%) patients, respectively. The primary endpoint of major adverse cardiac events (MACE) at 6 months was 5.5% vs 2.2% (risk differences 3.2%, 95% CI -0.2 to 6.8, p=0.07) and at 2 years 12.9% vs 8.4% (HR 0.63, 95% CI 0.35 to 1.13, p = 0.12) after simple versus complex treatment. In the subgroup treated by newer generation drug-eluting stents, MACE was 12.0% vs 5.6% (HR 0.45, 95% CI 0.17 to 1.17, p = 0.10) after simple versus complex treatment.Conclusion: In the treatment of bifurcation lesions involving a large SB with ostial stenosis, routine two-stent techniques did not improve outcome significantly compared with treatment by the simpler main vessel stenting technique after 2 years.
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28.
  • Madsen, Jasmine Melissa, et al. (författare)
  • Clinical outcomes of no stenting in patients with ST-segment elevation myocardial infarction undergoing deferred primary percutaneous coronary intervention
  • 2022
  • Ingår i: EuroIntervention. - 1774-024X. ; 18:6, s. 482-491
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: ST-segment elevation myocardial infarction (STEMI) is treated with stenting, but the underlying stenosis is often not severe, and stenting may potentially be omitted. Aims: The aim of the study was to investigate outcomes of patients with STEMI treated with percutaneous coronary intervention (PCI) without stenting. Methods: Patients were identified through the DANAMI-3-DEFER study. Stenting was omitted in the patients with stable flow after initial PCI and no significant residual stenosis on the deferral procedure, who were randomised to deferred stenting. These patients were compared to patients randomised to conventional PCI treated with immediate stenting. The primary endpoint was a composite of all-cause mortality, recurrent myocardial infarction (MI), and target vessel revascularisation (TVR). Results: Of 603 patients randomised to deferred stenting, 84 were treated without stenting, and in patients randomised to conventional PCI (n=612), 590 were treated with immediate stenting. Patients treated with no stenting had a median stenosis of 40%, median vessel diameter of 2.9 mm, and median lesion length of 11.4 mm. During a median follow-up of 3.4 years, the composite endpoint occurred in 14% and 16% in the no and immediate stenting groups, respectively (unadjusted hazard ratio [HR] 0.87, 95% confidence interval [CI]: 0.48-1.60; p=0.66). The association remained non-significant after adjusting for confounders (adjusted HR 0.53, 95% CI: 0.22-1.24; p=0.14). The rates of TVR and recurrent MI were 2% vs 4% (p=0.70) and 4% vs 6% (p=0.43), respectively. Conclusions: Patients with STEMI, with no significant residual stenosis and stable flow after initial PCI, treated without stenting, had comparable event rates to patients treated with immediate stenting.
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29.
  • Madsen, Jasmine Melissa, et al. (författare)
  • Comparison of Effect of Ischemic Postconditioning on Cardiovascular Mortality in Patients With ST-Segment Elevation Myocardial Infarction Treated With Primary Percutaneous Coronary Intervention With Versus Without Thrombectomy
  • 2022
  • Ingår i: American Journal of Cardiology. - : Elsevier BV. - 0002-9149. ; 166, s. 18-24
  • Tidskriftsartikel (refereegranskat)abstract
    • In patients with ST-segment elevation myocardial infarction (STEMI), ischemic postconditioning (iPOST) have shown ambiguous results in minimizing reperfusion injury. Previous findings show beneficial effects of iPOST in patients with STEMI treated without thrombectomy. However, it remains unknown whether the cardioprotective effect of iPOST in these patients persist on long term. In the current study, all patients were identified through the DANAMI-3-iPOST database. Patients were randomized to conventional primary percutaneous coronary intervention (PCI) or iPOST in addition to PCI. Cumulative incidence rates were calculated, and multivariable analyses stratified according to thrombectomy use were performed. The primary end point was a combination of cardiovascular mortality and hospitalization for heart failure. From 2011 to 2014, 1,234 patients with STEMI were included with a median follow-up of 4.8 years. In patients treated without thrombectomy (n = 520), the primary end point occurred in 15% (48/326) in the iPOST group and in 22% (42/194) in the conventional group (unadjusted hazard ratio [HR] 0.62, 95% confidence interval [CI] 0.41 to 0.94, p = 0.023). In adjusted Cox analysis, iPOST remained associated with reduced long-term risk of cardiovascular mortality (HR 0.53, 95% CI 0.29 to 0.97, p = 0.039). In patients treated with thrombectomy (n = 714), there was no significant difference between iPOST (17%, 49/291) and conventional treatment (17%, 72/423) on the primary end point (unadjusted HR 1.01, 95% CI 0.70 to 1.45, p = 0.95). During a follow-up of nearly 5 years, iPOST reduced long-term occurrence of cardiovascular mortality and hospitalization for heart failure in patients with STEMI treated with PCI but without thrombectomy.
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30.
  • Madsen, Jasmine Melissa, et al. (författare)
  • Long-term prognostic outcomes and implication of oral anticoagulants in patients with new-onset atrial fibrillation following st-segment elevation myocardial infarction
  • 2021
  • Ingår i: American Heart Journal. - : Elsevier BV. - 0002-8703. ; 238, s. 89-99
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: New-onset atrial fibrillation (NEW-AF) following ST-segment elevation myocardial infarction (STEMI) is a common complication, but the true prognostic impact of NEW-AF is unknown. Additionally, the optimal treatment of NEW-AF among patients with STEMI is warranted. Methods: A large cohort of consecutive patients with STEMI treated with percutaneous coronary intervention were identified using the Eastern Danish Heart Registry from 1999-2016. Medication and end points were retrieved from Danish nationwide registries. NEW-AF was defined as a diagnosis of AF within 30 days following STEMI. Patients without a history of AF and alive after 30 days after discharge were included. Incidence rates were calculated and multivariate analyses performed to determine the association between NEW-AF and long-term mortality, incidence of ischemic stroke, re-MI, and bleeding leading to hospitalization, and the comparative effectiveness of OAC therapy on these outcomes. Results: Of 7944 patients with STEMI, 296 (3.7%) developed NEW-AF. NEW-AF was associated with increased long-term mortality (adjusted HR 1.48, 95% CI 1.20-1.82, P<.001) and risk of bleeding leading to hospitalization (adjusted HR 1.36, 95% CI 1.00-1.85, P=.050), and non-significant increased risk of ischemic stroke (adjusted HR 1.45, 95% CI 0.96-2.19, P=.08) and re-MI (adjusted HR 1.14, 95% CI 0.86-1.52, P=.35) with a median follow-up of 5.8 years. In NEW-AF patients, 38% received OAC therapy, which was associated with reduced long-term mortality (adjusted HR 0.69, 95% CI 0.47-1.00, P=.049). Conclusions: NEW-AF following STEMI is associated with increased long-term mortality. Treatment with OAC therapy in NEW-AF patients is associated with reduced long-term mortality.
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31.
  • Mohammad, Moman A., et al. (författare)
  • On the Natural History of Coronary Artery Disease : A Longitudinal Nationwide Serial Angiography Study
  • 2022
  • Ingår i: Journal of the American Heart Association. - : John Wiley & Sons. - 2047-9980 .- 2047-9980. ; 11:21
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: The long-term course of coronary atherosclerosis has not been studied in large nationwide cohorts. Understanding the natural history of coronary atherosclerosis could help identify patients at risk for future coronary events.Methods and Results: All coronary artery segments with <50% luminal stenosis in patients with a first-time coronary angiogram between 1989 and 2017 were identified (n=2 661 245 coronary artery segments in 248 736 patients) and followed until a clinically indicated angiography within 15 years was performed or until death or end of follow-up (April 2018) using SCAAR (Swedish Coronary Angiography and Angioplasty Registry). The stenosis progression and incidence rates were 2.6% and 1.45 (95% CI, 1.43-1.46) per 1000 segment-years, respectively. The greatest progression rate occurred in the proximal and middle segments of the left anterior descending artery. Male sex and diabetes were associated with a 2-fold increase in risk, and nearly 70% of new stenoses occurred in patients with baseline single-vessel disease (hazard ratio, 3.86 [95% CI, 3.69-4.04]). Coronary artery segments in patients with no baseline risk factors had a progression rate of 0.6% and incidence rate of 0.36 (95% CI, 0.34-0.39), increasing to 8.1% and 4.01 (95% CI, 3.89-4.14) per 1000 segment-years, respectively, in patients with ≥4 risk factors. The prognostic impact of risk factors on stenosis progression was greatest in younger patients and women.Conclusions: Coronary atherosclerosis progressed slowly but more frequently in the left coronary artery in men and in the presence of traditional risk factors. Coronary artery segments in patients without risk factors had little or no risk of stenosis progression, and the relative impact of risk factors appears to be of greater importance in younger patients and women. These findings help in the understanding the long-term course of coronary atherosclerosis.
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32.
  • Mohammad, Moman A., et al. (författare)
  • Usefulness of High Sensitivity Troponin T to Predict Long-Term Left Ventricular Dysfunction After ST-Elevation Myocardial Infarction
  • 2020
  • Ingår i: American Journal of Cardiology. - : Elsevier BV. - 0002-9149. ; 134, s. 8-13
  • Tidskriftsartikel (refereegranskat)abstract
    • Guidelines recommend the use of transthoracic echocardiography (TTE) and clinical scores to risk stratify patients after ST-elevation myocardial infarction (STEMI). High sensitivity troponin T (hs-cTnT) is predictive of outcome after STEMI but the predictive value of hs-cTnT relative to other risk assessment tools has not been established. We aimed to compare the predictive value of hs-cTnT to other risk assessment tools in patients with STEMI. A subset of 578 patients with STEMI were included in this post-hoc study from the Third DANish Study of Optimal Acute Treatment of Patients with ST-segment Elevation Myocardial Infarction trial. Patients underwent cardiac magnetic resonance imaging (CMR) during index hospitalization as well as TTE at 1 year after their STEMI. The predictive value of hs-cTnT was compared with CKMB, infarct size (IS)/left ventricular ejection fraction (LVEF) assessed with CMR, LVEF assessed at discharge with TTE and the Global Registry of Acute Coronary Events (GRACE) and Thrombolysis in Myocardial Infarction (TIMI) risk-scores. The primary outcome was LV systolic dysfunction defined as LVEF ≤40% after 1 year on TTE. The area under the receiver operating characteristic curve analyses showed no significant difference between hs-cTnT and early CMR-assessed IS or LVEF in predicting subsequent LVEF ≤40%. Area under the curve for hs-cTnT was 0.82, 0.85 for IS (p = 0.22), and 0.87 for LVEF (p = 0.23). For predischarge TTE-assessed LVEF, the value was 0.85 (p = 0.45), 0.63 for creatine kinase-MB (p <0.001), 0.61 for the GRACE score (p <0.001), and 0.70 for the TIMI score (p = 0.02). A peak hs-cTnT value <3,500 ng/L ruled out LVEF ≤40% with probability of 98%. In conclusion, in patients presenting with STEMI undergoing PCI, hs-cTnT level strongly predicted long-term LV dysfunction and could be used as a clinical risk stratification tool to identify patients at high risk of progressing to LV dysfunction due to its general availability and high-predictive accuracy.
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33.
  • Mohammad, Moman A., et al. (författare)
  • Using proximity extension proteomics assay to identify biomarkers associated with infarct size and ejection fraction after ST-elevation myocardial infarction
  • 2020
  • Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 10:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Plasma concentrations of many cardiovascular and inflammatory proteins are altered after ST-elevation myocardial infarction (STEMI) and may provide prognostic information. We conducted a large-scale proteomic analysis in patients with STEMI, correlating protein levels to infarct size and left ventricular ejection fraction (LVEF) determined with cardiac magnetic resonance imaging. We analysed 131 cardiovascular and inflammatory proteins using a multiplex proximity extension assay and blood samples obtained at baseline, 6, 24, and 96 h from the randomised clinical trial CHILL-MI. Cardiac magnetic resonance imaging data at 4 ± 2 days and 6 months were available as per trial protocol. Using a linear regression model with bootstrap resampling and false discovery rate adjustment we identified five proteins (ST2, interleukin-6, pentraxin-3, interleukin-10, renin, and myoglobin) with elevated values corresponding to larger infarct size or worse LVEF and four proteins (TNF-related apoptosis-inducing ligand, TNF-related activation induced cytokine, interleukin-16, and cystatin B) with values inversely related to LVEF and infarct size, concluding that among 131 circulating inflammatory and cardiovascular proteins in the acute and sub-acute phase of STEMI, nine showed a relationship with infarct size and LVEF post-STEMI, with IL-6 and ST2 exhibiting the strongest association.
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34.
  • Nepper-Christensen, Lars, et al. (författare)
  • Clinical outcome following late reperfusion with percutaneous coronary intervention in patients with ST-segment elevation myocardial infarction
  • 2021
  • Ingår i: European Heart Journal: Acute Cardiovascular Care. - : Oxford University Press (OUP). - 2048-8726 .- 2048-8734. ; 10:5, s. 523-531
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Up to 40% of patients with ST-segment elevation myocardial infarction (STEMI) present later than 12 hours after symptom onset. However, data on clinical outcomes in STEMI patients treated with primary percutaneous coronary intervention (PCI) ≥12 hours after symptom onset are non-existent. We evaluated the association between primary PCI performed later than 12 hours after symptom onset and clinical outcomes in a large all-comer contemporary STEMI cohort. Methods: All STEMI patients treated with primary PCI in eastern Denmark from November 2009 to November 2016 were included and stratified by timing of the PCI. The combined clinical endpoint of all-cause mortality and hospitalisation for heart failure was identified from nationwide Danish registries. Results: We included 6674 patients: 6108 (92%) were treated <12 hours and 566 (8%) were treated ≥12 hours after symptom onset. During a median follow-up period of 3.8 (interquartile range 2.3-5.6) years, 30-day, one-year and long-term cumulative rates of the combined endpoint were 11%, 17% and 25% in patients treated <12 hours and 21%, 29% and 37% in patients treated ≥12 hours after symptom onset (P > 0.001 for all). Late presentation was independently associated with an increased risk of an adverse clinical outcome (hazard ratio 1.42, 95% confidence interval 1.22-1.66; P < 0.001). Conclusions: Increasing duration from symptom onset to primary PCI was associated with an increased risk of an adverse clinical outcome in patients with STEMI, especially when the delay exceeded 12 hours.
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35.
  • Panezai, Jeneen, et al. (författare)
  • Periodontal Disease Augments Cardiovascular Disease Risk Biomarkers in Rheumatoid Arthritis
  • 2022
  • Ingår i: Biomedicines. - : MDPI. - 2227-9059. ; 10:3
  • Tidskriftsartikel (refereegranskat)abstract
    • OBJECTIVES: Periodontal disease (PD) and rheumatoid arthritis (RA) are known chronic conditions with sustained inflammation leading to osteolysis. Cardiovascular diseases (CVD) are frequent comorbidities that may arise from sustained inflammation associated with both PD and RA. In order to determine CVD risk, alterations at the molecular level need to be identified. The objective of this study, therefore, was to assess the relationship of CVD associated biomarkers in RA patients and how it is influenced by PD.METHODS: The study consisted of patient (26 RA with PD, 21 RA without PD, 51 patients with PD only) and systemically and periodontally healthy control (n = 20) groups. Periodontal parameters bleeding on probing, probing pocket depth, and marginal bone loss were determined to characterize the patient groups. Proteomic analysis of 92 CVD-related protein biomarkers was performed using a multiplex proximity extension assay. Biomarkers were clustered using the search tool for retrieval of interacting genes (STRING) to determine protein-protein interaction (PPI) networks.RESULTS: RA patients with PD had higher detection levels for 47% of the measured markers (ANGPT1, BOC, CCL17, CCL3, CD4, CD84, CTRC, FGF-21, FGF-23, GLO1, HAOX1, HB-EGF, hOSCAR, HSP 27, IL16, IL-17D, IL18, IL-27, IL6, LEP, LPL, MERTK, MMP12, MMP7, NEMO, PAPPA, PAR-1, PARP-1, PD-L2, PGF, PIgR, PRELP, RAGE, SCF, SLAMF7, SRC, THBS2, THPO, TNFRSF13B, TRAIL-R2, VEGFD, VSIG2, and XCL1) as compared to RA without PD. Furthermore, a strong biological network was identified amongst these proteins (clustering coefficient = 0.52, PPI enrichment p-value < 0.0001). Coefficients for protein clusters involved in CVD (0.59), metabolic (0.53), and skeletal (0.51) diseases were strongest in the PD group.CONCLUSION: Periodontal disease augments CVD-related biomarkers in RA through shared pathological clusters, concurrently enhancing metabolic and skeletal disease protein interactions, independent of autoimmune status.
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36.
  • Ramos, Eunice, et al. (författare)
  • a retrospective of activities and advances to 2019 : a retrospective of activities and advances to 2019
  • 2021
  • Ingår i: Environmental Research Letters. - : IOP Publishing. - 1748-9326. ; 16:3
  • Forskningsöversikt (refereegranskat)abstract
    • Population growth, urbanization and economic development drive the use of resources. Securing access to essential services such as energy, water, and food, while achieving sustainable development, require that policy and planning processes follow an integrated approach. The 'Climate-, Land-, Energy- and Water-systems' (CLEWs) framework assists the exploration of interactions between (and within) CLEW systems via quantitative means. The approach was first introduced by the International Atomic Energy Agency to conduct an integrated systems analysis of a biofuel chain. The framework assists the exploration of interactions between (and within) CLEW systems via quantitative means. Its multi-institutional application to the case of Mauritius in 2012 initiated the deployment of the framework. A vast number of completed and ongoing applications of CLEWs span different spatial and temporal scales, discussing two or more resource interactions under different political contexts. Also, the studies vary in purpose. This shapes the methods that support CLEWs-type analyses. In this paper, we detail the main steps of the CLEWs framework in perspective to its application over the years. We summarise and compare key applications, both published in the scientific literature, as working papers and reports by international organizations. We discuss differences in terms of geographic scope, purpose, interactions represented, analytical approach and stakeholder involvement. In addition, we review other assessments, which contributed to the advancement of the CLEWs framework. The paper delivers recommendations for the future development of the framework, as well as keys to success in this type of evaluations.
  •  
37.
  • Ravn Jacobsen, Mia, et al. (författare)
  • Potassium Disturbances and Risk of Ventricular Fibrillation Among Patients With ST-Segment-Elevation Myocardial Infarction
  • 2020
  • Ingår i: Journal of the American Heart Association. - 2047-9980. ; 9:4
  • Tidskriftsartikel (refereegranskat)abstract
    • Background Potassium disturbances per se increase the risk of ventricular fibrillation (VF). Whether potassium disturbances in the acute phase of ST-segment-elevation myocardial infarction (STEMI) are associated with VF before primary percutaneous coronary intervention (PPCI) is uncertain. Methods and Results All consecutive STEMI patients were identified in the Eastern Danish Heart Registry from 1999 to 2016. Comorbidities and medication use were assessed from Danish nationwide registries. Potassium levels were collected immediately before PPCI start. Multivariate logistic models were performed to determine the association between potassium and VF. The main analysis included 8624 STEMI patients of whom 822 (9.5%) had VF before PPCI. Compared with 6693 (77.6%) patients with normokalemia (3.5-5.0 mmol/L), 1797 (20.8%) patients with hypokalemia (<3.5 mmol/L) were often women with fewer comorbidities, whereas 134 (1.6%) patients with hyperkalemia (>5.0 mmol/L) were older with more comorbidities. After adjustment, patients with hypokalemia and hyperkalemia had a higher risk of VF before PPCI (odds ratio 1.90, 95% CI 1.57-2.30, P<0.001) and (odds ratio 3.36, 95% CI 1.95-5.77, P<0.001) compared with normokalemia, respectively. Since the association may reflect a post-resuscitation phenomenon, a sensitivity analysis was performed including 7929 STEMI patients without VF before PPCI of whom 127 (1.6%) had VF during PPCI. Compared with normokalemia, patients with hypokalemia had a significant association with VF during PPCI (odds ratio 1.68, 95% CI 1.01-2.77, P=0.045) after adjustment. Conclusions Hypokalemia and hyperkalemia are associated with increased risk of VF before PPCI during STEMI. For hypokalemia, the association may be independent of the measurement of potassium before or after VF.
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38.
  • Sabbah, Muhammad, et al. (författare)
  • Routine revascularization with percutaneous coronary intervention in patients with coronary artery disease undergoing transcatheter aortic valve implantation - the third Nordic Aortic Valve Intervention Trial - NOTION-3.
  • 2022
  • Ingår i: American heart journal. - : Elsevier BV. - 1097-6744 .- 0002-8703.
  • Tidskriftsartikel (refereegranskat)abstract
    • Coronary artery disease (CAD) frequently coexists with severe aortic valve stenosis (AS) in patients planned for transcatheter aortic valve implantation (TAVI). How to manage CAD in this patient population is still an unresolved question. In particular, it is still not known whether fractional flow reserve (FFR) guided revascularization with percutaneous coronary intervention (PCI) is superior to medical treatment for CAD in terms of clinical outcomes.The third Nordic Aortic Valve Intervention (NOTION-3) Trial is an open-label investigator-initiated, multicenter multinational trial planned to randomize 452 patients with severe AS and significant CAD to either FFR-guided PCI or medical treatment, in addition to TAVI. Patients are eligible for the study in the presence of at least one significant PCI-eligible coronary stenosis. A significant stenosis is defined as either FFR ≤0.80 and/or diameter stenosis >90%. The primary endpoint is a composite of first occurring all-cause mortality, myocardial infarction, or urgent revascularization (PCI or coronary artery bypass graft performed during unplanned hospital admission) until the last included patient have been followed for 1 year after the TAVI.NOTION-3 is a multicenter, multinational randomized trial aiming at comparing FFR-guided revascularization vs medical treatment of CAD in patients with severe AS planned for TAVI.
  •  
39.
  • Sabbah, Muhammad, et al. (författare)
  • Routine revascularization with percutaneous coronary intervention in patients with coronary artery disease undergoing transcatheter aortic valve implantation – the third nordic aortic valve intervention trial – NOTION-3
  • 2023
  • Ingår i: American Heart Journal. - : Elsevier BV. - 0002-8703 .- 1097-6744. ; 255, s. 39-51
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Coronary artery disease (CAD) frequently coexists with severe aortic valve stenosis (AS) in patients planned for transcatheter aortic valve implantation (TAVI). How to manage CAD in this patient population is still an unresolved question. In particular, it is still not known whether fractional flow reserve (FFR) guided revascularization with percutaneous coronary intervention (PCI) is superior to medical treatment for CAD in terms of clinical outcomes. Study design: The third Nordic Aortic Valve Intervention (NOTION-3) Trial is an open-label investigator-initiated, multicenter multinational trial planned to randomize 452 patients with severe AS and significant CAD to either FFR-guided PCI or medical treatment, in addition to TAVI. Patients are eligible for the study in the presence of at least 1 significant PCI-eligible coronary stenosis. A significant stenosis is defined as either FFR ≤0.80 and/or diameter stenosis >90%. The primary end point is a composite of first occurring all-cause mortality, myocardial infarction, or urgent revascularization (PCI or coronary artery bypass graft performed during unplanned hospital admission) until the last included patient have been followed for 1 year after the TAVI. NOTION-3 is a multicenter, multinational randomized trial aiming at comparing FFR-guided revascularization vs medical treatment of CAD in patients with severe AS planned for TAVI.
  •  
40.
  • Stone, Gregg W., et al. (författare)
  • Percutaneous Coronary Intervention for Vulnerable Coronary Atherosclerotic Plaque
  • 2020
  • Ingår i: Journal of the American College of Cardiology. - : Elsevier BV. - 0735-1097 .- 1558-3597. ; 76:20, s. 2289-2301
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Acute coronary syndromes most commonly arise from thrombosis of lipid-rich coronary atheromas that have large plaque burden despite angiographically appearing mild. Objectives: This study sought to examine the outcomes of percutaneous coronary intervention (PCI) of non–flow-limiting vulnerable plaques. Methods: Three-vessel imaging was performed with a combination intravascular ultrasound (IVUS) and near-infrared spectroscopy (NIRS) catheter after successful PCI of all flow-limiting coronary lesions in 898 patients presenting with myocardial infarction (MI). Patients with an angiographically nonobstructive stenosis not intended for PCI but with IVUS plaque burden of ≥65% were randomized to treatment of the lesion with a bioresorbable vascular scaffold (BVS) plus guideline-directed medical therapy (GDMT) versus GDMT alone. The primary powered effectiveness endpoint was the IVUS-derived minimum lumen area (MLA) at protocol-driven 25-month follow-up. The primary (nonpowered) safety endpoint was randomized target lesion failure (cardiac death, target vessel–related MI, or clinically driven target lesion revascularization) at 24 months. The secondary (nonpowered) clinical effectiveness endpoint was randomized lesion–related major adverse cardiac events (cardiac death, MI, unstable angina, or progressive angina) at latest follow-up. Results: A total of 182 patients were randomized (93 BVS, 89 GDMT alone) at 15 centers. The median angiographic diameter stenosis of the randomized lesions was 41.6%; by near-infrared spectroscopy–IVUS, the median plaque burden was 73.7%, the median MLA was 2.9 mm2, and the median maximum lipid plaque content was 33.4%. Angiographic follow-up at 25 months was completed in 167 patients (91.8%), and the median clinical follow-up was 4.1 years. The follow-up MLA in BVS-treated lesions was 6.9 ± 2.6 mm2 compared with 3.0 ± 1.0 mm2 in GDMT alone–treated lesions (least square means difference: 3.9 mm2; 95% confidence interval: 3.3 to 4.5; p < 0.0001). Target lesion failure at 24 months occurred in similar rates of BVS-treated and GDMT alone–treated patients (4.3% vs. 4.5%; p = 0.96). Randomized lesion–related major adverse cardiac events occurred in 4.3% of BVS-treated patients versus 10.7% of GDMT alone–treated patients (odds ratio: 0.38; 95% confidence interval: 0.11 to 1.28; p = 0.12). Conclusions: PCI of angiographically mild lesions with large plaque burden was safe, substantially enlarged the follow-up MLA, and was associated with favorable long-term clinical outcomes, warranting the performance of an adequately powered randomized trial. (PROSPECT ABSORB [Providing Regional Observations to Study Predictors of Events in the Coronary Tree II Combined with a Randomized, Controlled, Intervention Trial]; NCT02171065)
  •  
41.
  • Sun, Jiangming, et al. (författare)
  • Translating polygenic risk scores for clinical use by estimating the confidence bounds of risk prediction
  • 2021
  • Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 12, s. 5276-5276
  • Tidskriftsartikel (refereegranskat)abstract
    • A promise of genomics in precision medicine is to provide individualized genetic risk predictions. Polygenic risk scores (PRS), computed by aggregating effects from many genomic variants, have been developed as a useful tool in complex disease research. However, the application of PRS as a tool for predicting an individual's disease susceptibility in a clinical setting is challenging because PRS typically provide a relative measure of risk evaluated at the level of a group of people but not at individual level. Here, we introduce a machine-learning technique, Mondrian Cross-Conformal Prediction (MCCP), to estimate the confidence bounds of PRS-to-disease-risk prediction. MCCP can report disease status conditional probability value for each individual and give a prediction at a desired error level. Moreover, with a user-defined prediction error rate, MCCP can estimate the proportion of sample (coverage) with a correct prediction.
  •  
42.
  • Svensson, Thomas, et al. (författare)
  • Very short sleep duration reveals a proteomic fingerprint that is selectively associated with incident diabetes mellitus but not with incident coronary heart disease : a cohort study
  • 2024
  • Ingår i: BMC Medicine. - 1741-7015. ; 22:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: The molecular pathways linking short and long sleep duration with incident diabetes mellitus (iDM) and incident coronary heart disease (iCHD) are not known. We aimed to identify circulating protein patterns associated with sleep duration and test their impact on incident cardiometabolic disease. Methods: We assessed sleep duration and measured 78 plasma proteins among 3336 participants aged 46–68 years, free from DM and CHD at baseline, and identified cases of iDM and iCHD using national registers. Incident events occurring in the first 3 years of follow-up were excluded from analyses. Tenfold cross-fit partialing-out lasso logistic regression adjusted for age and sex was used to identify proteins that significantly predicted sleep duration quintiles when compared with the referent quintile 3 (Q3). Predictive proteins were weighted and combined into proteomic scores (PS) for sleep duration Q1, Q2, Q4, and Q5. Combinations of PS were included in a linear regression model to identify the best predictors of habitual sleep duration. Cox proportional hazards regression models with sleep duration quintiles and sleep-predictive PS as the main exposures were related to iDM and iCHD after adjustment for known covariates. Results: Sixteen unique proteomic markers, predominantly reflecting inflammation and apoptosis, predicted sleep duration quintiles. The combination of PSQ1 and PSQ5 best predicted sleep duration. Mean follow-up times for iDM (n = 522) and iCHD (n = 411) were 21.8 and 22.4 years, respectively. Compared with sleep duration Q3, all sleep duration quintiles were positively and significantly associated with iDM. Only sleep duration Q1 was positively and significantly associated with iCHD. Inclusion of PSQ1 and PSQ5 abrogated the association between sleep duration Q1 and iDM. Moreover, PSQ1 was significantly associated with iDM (HR = 1.27, 95% CI: 1.06–1.53). PSQ1 and PSQ5 were not associated with iCHD and did not markedly attenuate the association between sleep duration Q1 with iCHD. Conclusions: We here identify plasma proteomic fingerprints of sleep duration and suggest that PSQ1 could explain the association between very short sleep duration and incident DM.
  •  
43.
  • Tarp, Julie Bjerre, et al. (författare)
  • Vascular function in adults with cyanotic congenital heart disease
  • 2020
  • Ingår i: IJC Heart and Vasculature. - : Elsevier BV. - 2352-9067. ; 30
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Patients with cyanotic congenital heart disease (CCHD) may have a low burden of atherosclerosis. Endothelial dysfunction is an early stage of atherosclerosis and endothelial function is previously studied in smaller CCHD groups with different techniques and variable results. We aimed to examine endothelial function and carotid atherosclerosis in a larger group of CCHD patients. Methods: This multicentre study assessed endothelial function in adults with CCHD and controls by measuring the dilatory response of the brachial artery to post-ischemic hyperaemia (endothelium-dependent flow-mediated-vasodilatation (FMD)), and to nitroglycerin (endothelium-independent nitroglycerin-induced dilatation (NID)). Flow was measured at baseline and after ischaemia (reactive hyperaemia). Carotid-intima-media-thickness (CIMT), prevalence of carotid plaque and plaque thickness (cPT-max) were evaluated ultrasonographically. Lipoproteins, inflammatory and vascular markers, including sphingosine-1-phosphate (S1P) were measured. Results: Forty-five patients with CCHD (median age 50 years) and 45 matched controls (median age 52 years) were included. The patients presented with lower reactive hyperaemia (409 ± 114% vs. 611 ± 248%, p < 0.0001), however preserved FMD response compared to controls (106.5 ± 8.3% vs. 106.4 ± 6.1%, p = 0.95). In contrast, NID was lower in the patients (110.5 ± 6.1% vs. 115.1 ± 7.4%, p = 0.053). There was no difference in CIMT, carotid plaque or cPT-max. The patients presented with lower high-density-lipoprotein cholesterol, and higher level of inflammatory markers and S1P. Conclusion: Adults with CCHD had preserved FMD in the brachial artery, but impaired NID response and lower reactive hyperaemia than controls. The preserved FMD and the comparable prevalence of carotid atherosclerosis indicate that CCHD patients have the same risk of atherosclerosis as controls.
  •  
44.
  • Thim, Troels, et al. (författare)
  • Evaluation and Management of Nonculprit Lesions in STEMI
  • 2020
  • Ingår i: JACC: Cardiovascular Interventions. - : Elsevier BV. - 1936-8798. ; 13:10, s. 1145-1154
  • Forskningsöversikt (refereegranskat)abstract
    • Nonculprit lesions are frequently observed in patients with ST-segment elevation myocardial infarction. Results from recent randomized clinical trials suggest that complete revascularization after ST-segment elevation myocardial infarction improves outcomes. In this state-of-the-art paper, the authors review these trials and consider how best to determine which nonculprit lesions require revascularization and when this should be performed.
  •  
45.
  • Westin, Thomas, et al. (författare)
  • Activities to Support Sustainable Inclusive Game Design Processes
  • 2020
  • Ingår i: EAI Endorsed Transactions on Creative Technologies. - : EAI. - 2409-9708. ; 6:20
  • Tidskriftsartikel (refereegranskat)abstract
    • INTRODUCTION: The problem addressed in this work is the lack of knowledge of what inclusive game design would mean in practice within existing design processes of game companies. A pilot project was devised to involve both the game industry and disabled people.OBJECTIVES: The goal in this study was to identify activities that constitute the biggest obstacles to realising sustainable design processes for inclusive game design.METHODS: The study is mainly based on two full-day workshops with the game industry and three game studios, three organisations of disabled youth and authorities.RESULTS: Five activities were identified in the analysis of the workshops: 1) Find opportunities for inclusive game design; 2) Raise awareness about inclusive game design; 3) Handle integrity and security; 4) Recruit the right competence; and 5) Adapt workplaces and tools.CONCLUSION: The five main activities should be considered to achieve sustainable inclusive game design processes.
  •  
46.
  • Westin, Thomas, et al. (författare)
  • Towards Sustainable Inclusive Game Design Processes
  • 2020
  • Ingår i: Interactivity, Game Creation, Design, Learning, and Innovation. - Cham : Springer. - 9783030532932 - 9783030532949 ; , s. 390-396
  • Konferensbidrag (refereegranskat)abstract
    • While many studies have been done about creation of accessible games, they have mainly been conducted in an academic context and represents a gap between game research and the game industry. The pilot project presented in this paper (PowerUp) addresses inclusive design by involving both the game industry and disabled people. The goal is to identify activities that constitute the biggest obstacles to realising sustainable design processes for inclusive game de- sign (IGD). Four activities were identified through two full-day workshops with the game industry and game studios, disabled people and authorities: 1) Find op- portunities for IGD with disabled people; 2) Handle integrity and security of dis- abled people; 3) Recruit the right competence among disabled people; and 4) Adapt workplaces and tools for IGD processes. These activities are tentative and will hopefully be subject to discussion and further development to achieve sus- tainable inclusive game design.
  •  
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