| 1. |
- Deschasaux, M., et al.
(författare)
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Nutritional quality of food as represented by the FSAm-NPS nutrient profiling system underlying the Nutri-Score label and cancer risk in Europe: Results from the EPIC prospective cohort study
- 2018
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Ingår i: Plos Medicine. - : Public Library of Science (PLoS). - 1549-1676 .- 1549-1277. ; 15:9
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Tidskriftsartikel (refereegranskat)abstract
- Background Helping consumers make healthier food choices is a key issue for the prevention of cancer and other diseases. In many countries, political authorities are considering the implementation of a simplified labelling system to reflect the nutritional quality of food products. The Nutri-Score, a five-colour nutrition label, is derived from the Nutrient Profiling System of the British Food Standards Agency (modified version) (FSAm-NPS). How the consumption of foods with high/low FSAm-NPS relates to cancer risk has been studied in national/regional cohorts but has not been characterized in diverse European populations. This prospective analysis included 471,495 adults from the European Prospective Investigation into Cancer and Nutrition (EPIC, 1992-2014, median follow-up: 15.3 y), among whom there were 49,794 incident cancer cases (main locations: breast, n = 12,063; prostate, n = 6,745; colon-rectum, n = 5,806). Usual food intakes were assessed with standardized country-specific diet assessment methods. The FSAm-NPS was calculated for each food/beverage using their 100-g content in energy, sugar, saturated fatty acid, sodium, fibres, proteins, and fruits/vegetables/legumes/nuts. The FSAm-NPS scores of all food items usually consumed by a participant were averaged to obtain the individual FSAm-NPS Dietary Index (DI) scores. Multi-adjusted Cox proportional hazards models were computed. A higher FSAm-NPS DI score, reflecting a lower nutritional quality of the food consumed, was associated with a higher risk of total cancer (HRQ5 versus (Q1) = 1.07; 95% CI 1.03-1.10, P-trend < 0.001). Absolute cancer rates in those with high and low (quintiles 5 and 1) FSAm-NPS DI scores were 81.4 and 69.5 cases/10,000 person-years, respectively. Higher FSAm-NPS DI scores were specifically associated with higher risks of cancers of the colon-rectum, upper aerodigestive tract and stomach, lung for men, and liver and postmenopausal breast for women (all P < 0.05). The main study limitation is that it was based on an observational cohort using self-reported dietary data obtained through a single baseline food frequency questionnaire; thus, exposure misclassification and residual confounding cannot be ruled out. In this large multinational European cohort, the consumption of food products with a higher FSAm-NPS score (lower nutritional quality) was associated with a higher risk of cancer. This supports the relevance of the FSAm-NPS as underlying nutrient profiling system for front-of-pack nutrition labels, as well as for other public health nutritional measures.
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| 2. |
- Heggebo, L. C., et al.
(författare)
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Investigating survival, quality of life and cognition in PROton versus photon therapy for IDH-mutated diffuse grade 2 and 3 GLIOmas (PRO-GLIO): a randomised controlled trial in Norway and Sweden
- 2023
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Ingår i: Bmj Open. - : BMJ. - 2044-6055. ; 13:3
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Tidskriftsartikel (refereegranskat)abstract
- IntroductionThe use of proton therapy increases globally despite a lack of randomised controlled trials demonstrating its efficacy and safety. Proton therapy enables sparing of non-neoplastic tissue from radiation. This is principally beneficial and holds promise of reduced long-term side effects. However, the sparing of seemingly non-cancerous tissue is not necessarily positive for isocitrate dehydrogenase (IDH)-mutated diffuse gliomas grade 2-3, which have a diffuse growth pattern. With their relatively good prognosis, yet incurable nature, therapy needs to be delicately balanced to achieve a maximal survival benefit combined with an optimised quality of life.Methods and analysisPRO-GLIO (PROton versus photon therapy in IDH-mutated diffuse grade 2 and 3 GLIOmas) is an open-label, multicentre, randomised phase III non-inferiority study. 224 patients aged 18-65 years with IDH-mutated diffuse gliomas grade 2-3 from Norway and Sweden will be randomised 1:1 to radiotherapy delivered with protons (experimental arm) or photons (standard arm). First intervention-free survival at 2 years is the primary endpoint. Key secondary endpoints are fatigue and cognitive impairment, both at 2 years. Additional secondary outcomes include several survival measures, health-related quality of life parameters and health economy endpoints.Ethics and disseminationTo implement proton therapy as part of standard of care for patients with IDH-mutated diffuse gliomas grade 2-3, it should be deemed safe. With its randomised controlled design testing proton versus photon therapy, PRO-GLIO will provide important information for this patient population concerning safety, cognition, fatigue and other quality of life parameters. As proton therapy is considerably more costly than its photon counterpart, cost-effectiveness will also be evaluated. PRO-GLIO is approved by ethical committees in Norway (Regional Committee for Medical & Health Research Ethics) and Sweden (The Swedish Ethical Review Authority) and patient inclusion has commenced. Trial results will be published in international peer-reviewed journals, relevant conferences, national and international meetings and expert forums.Trial registration numberClinicalTrials.gov Registry (NCT05190172).
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| 3. |
- Dankiewicz, Josef, et al.
(författare)
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Hypothermia versus Normothermia after Out-of-Hospital Cardiac Arrest
- 2021
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Ingår i: New England Journal of Medicine. - : MASSACHUSETTS MEDICAL SOC. - 0028-4793 .- 1533-4406. ; 384:24, s. 2283-2294
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Tidskriftsartikel (refereegranskat)abstract
- Hypothermia or Normothermia after Cardiac Arrest This trial randomly assigned patients with coma after out-of-hospital cardiac arrest to undergo targeted hypothermia at 33 degrees C or normothermia with treatment of fever. At 6 months, there were no significant between-group differences regarding death or functional outcomes. Background Targeted temperature management is recommended for patients after cardiac arrest, but the supporting evidence is of low certainty. Methods In an open-label trial with blinded assessment of outcomes, we randomly assigned 1900 adults with coma who had had an out-of-hospital cardiac arrest of presumed cardiac or unknown cause to undergo targeted hypothermia at 33 degrees C, followed by controlled rewarming, or targeted normothermia with early treatment of fever (body temperature, >= 37.8 degrees C). The primary outcome was death from any cause at 6 months. Secondary outcomes included functional outcome at 6 months as assessed with the modified Rankin scale. Prespecified subgroups were defined according to sex, age, initial cardiac rhythm, time to return of spontaneous circulation, and presence or absence of shock on admission. Prespecified adverse events were pneumonia, sepsis, bleeding, arrhythmia resulting in hemodynamic compromise, and skin complications related to the temperature management device. Results A total of 1850 patients were evaluated for the primary outcome. At 6 months, 465 of 925 patients (50%) in the hypothermia group had died, as compared with 446 of 925 (48%) in the normothermia group (relative risk with hypothermia, 1.04; 95% confidence interval [CI], 0.94 to 1.14; P=0.37). Of the 1747 patients in whom the functional outcome was assessed, 488 of 881 (55%) in the hypothermia group had moderately severe disability or worse (modified Rankin scale score >= 4), as compared with 479 of 866 (55%) in the normothermia group (relative risk with hypothermia, 1.00; 95% CI, 0.92 to 1.09). Outcomes were consistent in the prespecified subgroups. Arrhythmia resulting in hemodynamic compromise was more common in the hypothermia group than in the normothermia group (24% vs. 17%, P<0.001). The incidence of other adverse events did not differ significantly between the two groups. Conclusions In patients with coma after out-of-hospital cardiac arrest, targeted hypothermia did not lead to a lower incidence of death by 6 months than targeted normothermia. (Funded by the Swedish Research Council and others; TTM2 ClinicalTrials.gov number, .)
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| 4. |
- Lilja, Gisela, et al.
(författare)
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Effects of Hypothermia vs Normothermia on Societal Participation and Cognitive Function at 6 Months in Survivors After Out-of-Hospital Cardiac Arrest A Predefined Analysis of the TTM2 Randomized Clinical Trial
- 2023
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Ingår i: Jama Neurology. - 2168-6149 .- 2168-6157. ; 80:10, s. 1070-1079
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Tidskriftsartikel (refereegranskat)abstract
- IMPORTANCE The Targeted Hypothermia vs Targeted Normothermia After Out-of-Hospital Cardiac Arrest (TTM2) trial reported no difference in mortality or poor functional outcome at 6 months after out-of-hospital cardiac arrest (OHCA). This predefined exploratory analysis provides more detailed estimation of brain dysfunction for the comparison of the 2 intervention regimens. OBJECTIVES To investigate the effects of targeted hypothermia vs targeted normothermia on functional outcome with focus on societal participation and cognitive function in survivors 6 months after OHCA. DESIGN, SETTING, AND PARTICIPANTS This study is a predefined analysis of an international multicenter, randomized clinical trial that took place from November 2017 to January 2020 and included participants at 61 hospitals in 14 countries. A structured follow-up for survivors performed at 6 months was by masked outcome assessors. The last follow-up took place in October 2020. Participants included 1861 adult (older than 18 years) patients with OHCA who were comatose at hospital admission. At 6 months, 939 of 1861 were alive and invited to a follow-up, of which 103 of 939 declined or were missing. INTERVENTIONS Randomization 1:1 to temperature control with targeted hypothermia at 33 degrees C or targeted normothermia and early treatment of fever (37.8 degrees C or higher). MAIN OUTCOMES AND MEASURES Functional outcome focusing on societal participation assessed by the Glasgow Outcome Scale Extended ([GOSE] 1 to 8) and cognitive function assessed by the Montreal Cognitive Assessment ([MoCA] 0 to 30) and the Symbol Digit Modalities Test ([SDMT] z scores). Higher scores represent better outcomes. RESULTS At 6 months, 836 of 939 survivors with a mean age of 60 (SD, 13) (range, 18 to 88) years (700 of 836 male [84%]) participated in the follow-up. There were no differences between the 2 intervention groups in functional outcome focusing on societal participation (GOSE score, odds ratio, 0.91; 95% CI, 0.71-1.17; P =.46) or in cognitive function by MoCA (mean difference, 0.36; 95% CI,-0.33 to 1.05; P =.37) and SDMT (mean difference, 0.06; 95% CI,-0.16 to 0.27; P =.62). Limitations in societal participation (GOSE score less than 7) were common regardless of intervention (hypothermia, 178 of 415 [43%]; normothermia, 168 of 419 [40%]). Cognitive impairment was identified in 353 of 599 survivors (59%). CONCLUSIONS In this predefined analysis of comatose patients after OHCA, hypothermia did not lead to better functional outcome assessed with a focus on societal participation and cognitive function than management with normothermia. At 6 months, many survivors had not regained their pre-arrest activities and roles, and mild cognitive dysfunction was common.
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| 5. |
- Dankiewicz, Josef, et al.
(författare)
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Targeted hypothermia versus targeted Normothermia after out-of-hospital cardiac arrest (TTM2): A randomized clinical trial - Rationale and design
- 2019
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Ingår i: American Heart Journal. - : Elsevier BV. - 0002-8703 .- 1097-6744. ; 217, s. 23-31
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Tidskriftsartikel (refereegranskat)abstract
- Background: Less than 500 participants have been included in randomized trials comparing hypothermia with regular care for out-of-hospital cardiac arrest patients, and many of these trials were small and at a high risk of bias. Consequently, the accrued data on this potentially beneficial intervention resembles that of a drug following small phase II trials. A large confirmatory trial is therefore warranted. Methods: The TTM2-trial is an international, multicenter, parallel group, investigator-initiated, randomized, superiority trial in which a target temperature of 33°C after cardiac arrest will be compared with a strategy to maintain normothermia and early treatment of fever (≥37.8°C). Participants will be randomized within 3 hours of return of spontaneous circulation with the intervention period lasting 40 hours in both groups. Sedation will be mandatory for all patients throughout the intervention period. The clinical team involved with direct patient care will not be blinded to allocation group due to the inherent difficulty in blinding the intervention. Prognosticators, outcome-assessors, the steering group, the trial coordinating team, and trial statistician will be blinded. The primary outcome will be all-cause mortality at 180 days after randomization. We estimate a 55% mortality in the control group. To detect an absolute risk reduction of 7.5% with an alpha of 0.05 and 90% power, 1900 participants will be enrolled. The main secondary neurological outcome will be poor functional outcome (modified Rankin Scale 4–6) at 180 days after arrest. Discussion: The TTM2-trial will compare hypothermia to 33°C with normothermia and early treatment of fever (≥37.8°C) after out-of-hospital cardiac arrest. © 2019
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| 6. |
- Rosengren, B., et al.
(författare)
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Secretory phospholipase A2 group V: lesion distribution, activation by arterial proteoglycans, and induction in aorta by a Western diet
- 2006
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Ingår i: Arterioscler Thromb Vasc Biol. - 1524-4636. ; 26:7, s. 1579-85
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: To study the distribution of group V secretory phospholipase A2 (sPLA2) in human and mouse lesions and compare its expression by human vascular cells, its activity toward lipoproteins, and the interaction with arterial proteoglycans (proteoglycans) with those of sPLA2-IIA. In addition, we also investigated the effect of a Western diet and lipopolysaccharide challenge on the aortic expression of these enzymes in mouse models. METHODS AND RESULTS: Immunohistochemistry showed sPLA2-V in human and mouse lesions to be associated with smooth muscle cells and also surrounding foam cells in lipid core areas. mRNA of the enzyme was expressed in human lesions and human vascular cells, supporting the immunohistochemistry data. sPLA2-V but not sPLA2-IIA was active on lipoproteins in human serum. The association with proteoglycans enhanced 2- to 3-fold sPLA2-V activity toward low-density lipoproteins but not that of the group IIA enzyme. Experiments in mouse models showed that treatment with a Western diet induced expression of sPLA2-V but not that of sPLA2-IIA in aorta. On the other hand, lipopolysaccharide-induced acute inflammation augmented the expression of sPLA2-IIA but not that of sPLA2-V. CONCLUSIONS: These results indicate that these phospholipases could have different roles in atherosclerosis.
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| 7. |
- Adingupu, D. D., et al.
(författare)
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Radial artery intima-media thickness regresses after secondary prevention interventions in patients' post-acute coronary syndrome and is associated with cardiac and kidney biomarkers
- 2017
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Ingår i: Oncotarget. - : Impact Journals, LLC. - 1949-2553. ; 8:32, s. 53419-53431
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Tidskriftsartikel (refereegranskat)abstract
- Background: Radial artery intima-media thickness (rIMT) measured by ultra-high-resolution ultrasound is associated with increased cardiovascular risk and predicts outcomes. We performed non-invasive high-resolution ultrasound of the radial artery to investigate vascular changes in subjects presenting with acute coronary syndrome (ACS) and who had undergone percutaneous coronary intervention (PCI). Purpose: In the present work, we aimed to follow rIMT change over time post-acute coronary syndrome as a tool to monitor potential response to intensified medical therapy. Methods: We examined 256 subjects who underwent PCI due to ACS and healthy controls (n= 39) and we measured a number of biomarkers, which are known to be associated with cardiovascular disease. Images of radial artery were acquired bilaterally in the longitudinal view using a 50 MHz transducer (Vevo 2100 VisualSonics, Inc, Toronto, Ontario, Canada). Carotid IMT (cIMT) and rIMT were measured at <1 month after index PCI followed by a repeated measurement of rIMT at 4 months from the ACS in a sub-set (n= 117). Results: rIMT measured within 1 month post ACS was significantly higher than rIMT after 4 months from ACS, (p < 0.0001), mean +/- SD (rIMT right 0.35 +/- 0.08; rIMT left 0.37 +/- 0.08) vs. (rIMT right 0.29 +/- 0.08; rIMT left 0.31 +/- 0.09) respectively. There was no statistically significant change in cIMT. In healthy controls there were no changes in rIMT or cIMT overtime. High levels of CX3CL1 and myeloperoxidase measured within one month post ACS are associated with increase of rIMT, r=0.38 (p< 0.0001) and r=0.41 (p< 0.0001) respectively. Conclusions: rIMT seem to decrease systemically after ACS and is accompanied with corresponding biomarker change. The cause and clinical implications of the observed decrement in rIMT after ACS need further studies.
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| 8. |
- Adingupu, D. D., et al.
(författare)
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SGLT2 inhibition with empagliflozin improves coronary microvascular function and cardiac contractility in prediabetic ob/ob(-/-) mice
- 2019
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Ingår i: Cardiovascular Diabetology. - : Springer Science and Business Media LLC. - 1475-2840. ; 18
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundSodium-glucose cotransporter 2 inhibitors (SGLT2i) is the first class of anti-diabetes treatment that reduces mortality and risk for hospitalization due to heart failure. In clinical studies it has been shown that SGLT2i's promote a general shift to fasting state metabolism characterized by reduced body weight and blood glucose, increase in glucagon/insulin ratio and modest increase in blood ketone levels. Therefore, we investigated the connection between metabolic changes and cardiovascular function in the ob/ob(-/-) mice; a rodent model of early diabetes with specific focus on coronary microvascular function. Due to leptin deficiency these mice develop metabolic syndrome/diabetes and hepatic steatosis. They also develop cardiac contractile and microvascular dysfunction and are thus a promising model for translational studies of cardiometabolic diseases. We investigated whether this mouse model responded in a human-like manner to empagliflozin treatment in terms of metabolic parameters and tested the hypothesis that it could exert direct effects on coronary microvascular function and contractile performance.MethodsLean, ob/ob(-/-) untreated and ob/ob(-/-) treated with SGLT2i were followed for 10weeks. Coronary flow velocity reserve (CFVR) and fractional area change (FAC) were monitored with non-invasive Doppler ultrasound imaging. Food intake, urinary glucose excursion and glucose control via HbA1c measurements were followed throughout the study. Liver steatosis was assessed by histology and metabolic parameters determined at the end of the study.ResultsSodium-glucose cotransporter 2 inhibitors treatment of ob/ob(-/-) animals resulted in a switch to a more catabolic state as observed in clinical studies: blood cholesterol and HbA1c were decreased whereas glucagon/insulin ratio and ketone levels were increased. SGLT2i treatment reduced liver triglyceride, steatosis and alanine aminotransferase, an indicator for liver dysfunction. l-Arginine/ADMA ratio, a marker for endothelial function was increased. SGLT2i treatment improved both cardiac contractile function and coronary microvascular function as indicated by improvement of FAC and CFVR, respectively.ConclusionsSodium-glucose cotransporter 2 inhibitors treatment of ob/ob(-/-) mice mimics major clinical findings regarding metabolism and cardiovascular improvements and is thus a useful translational model. We demonstrate that SGLT2 inhibition improves coronary microvascular function and contractile performance, two measures with strong predictive values in humans for CV outcome, alongside with the known metabolic changes in a preclinical model for prediabetes and heart failure.
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| 9. |
- Bonde, J P E, et al.
(författare)
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Occupational risk of COVID-19 in foreign-born employees in Denmark
- 2023
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Ingår i: Occupational Medicine. - : Oxford University Press. - 0962-7480 .- 1471-8405.
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Foreign-born workers in high-income countries experience higher rates of COVID-19 but the causes are only partially known. AIMS: To examine if the occupational risk of COVID-19 in foreign-born workers deviates from the risk in native-born employees in Denmark. METHODS: Within a registry-based cohort of all residents employed in Denmark (n = 2 451 542), we identified four-digit DISCO-08 occupations associated with an increased incidence of COVID-19-related hospital admission during 2020-21 (at-risk occupations). The sex-specific prevalence of at-risk employment in foreign born was compared with the prevalence in native born. Moreover, we examined if the country of birth modified the risk of a positive SARS-CoV-2 polymerase chain reaction (PCR) test and COVID-19-related hospital admission in at-risk occupations. RESULTS: Workers born in low-income countries and male workers from Eastern Europe more often worked in at-risk occupations (relative risks between 1.16 [95% confidence interval {CI} 1.14-1.17] and 1.87 [95% CI 1.82-1.90]). Being foreign-born modified the adjusted risk of PCR test positivity (test for interaction P < 0.0001), primarily because of higher risk in at-risk occupations among men born in Eastern European countries (incidence rate ratio [IRR] 2.39 [95% CI 2.09-2.72] versus IRR 1.19 [95% CI 1.14-1.23] in native-born men). For COVID-19-related hospital admission, no overall interaction was seen, and in women, country of birth did not consistently modify the occupational risk. CONCLUSIONS: Workplace viral transmission may contribute to an excess risk of COVID-19 in male workers born in Eastern Europe, but most foreign-born employees in at-risk occupations seem not to be at higher occupational risk than native born.
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| 10. |
- da Silva, M., et al.
(författare)
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Excess body weight, weight gain and obesity-related cancer risk in women in Norway: the Norwegian Women and Cancer study
- 2018
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Ingår i: British Journal of Cancer. - : Springer Science and Business Media LLC. - 0007-0920 .- 1532-1827. ; 119:5, s. 646-656
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Excess body weight and weight gain have been reported to independently increase the risk of several cancers. There are few published studies in nationally representative populations of women on specific, 'obesity-related' cancers in relation to prior weight change and relevant confounders. METHODS: Based on self-reported anthropometry, we prospectively assessed body mass index (BMI), weight change over 6 years and subsequent obesity-related cancer risk in the Norwegian Women and Cancer study. We used Cox proportional hazard models to calculate hazard ratios and restricted cubic splines to model potential non-linear dose-response relationships. RESULTS: Excess body weight increased the risk of overall obesity-related cancer, postmenopausal breast, colorectal, colon, endometrial and kidney cancer, with endometrial cancer showing a threefold elevated risk. High weight gain (>= 10 kg) increased the risk of overall obesity-related cancer, postmenopausal breast, endometrial and pancreatic cancer. The association between high weight gain and pancreatic cancer was strong, with 91% increased risk. CONCLUSIONS: Maintaining stable weight in middle adulthood, irrespective of BMI category at baseline, and avoiding excess body weight are both important in the prevention of several obesity-related cancers in women. Our finding of increased risk of pancreatic cancer in women with moderate and high weight gain is novel.
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