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- Wilman, H. R., et al.
(författare)
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Genetic studies of abdominal MRI data identify genes regulating hepcidin as major determinants of liver iron concentration
- 2019
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Ingår i: Journal of Hepatology. - : Elsevier. - 0168-8278 .- 1600-0641. ; 71:3, s. 594-602
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Tidskriftsartikel (refereegranskat)abstract
- Background & Aims: Excess liver iron content is common and is linked to the risk of hepatic and extrahepatic diseases. We aimed to identify genetic variants influencing liver iron content and use genetics to understand its link to other traits and diseases. Methods: First, we performed a genome-wide association study (GWAS) in 8,289 individuals from UK Biobank, whose liver iron level had been quantified by magnetic resonance imaging, before validating our findings in an independent cohort (n = 1,513 from IMI DIRECT). Second, we used Mendelian randomisation to test the causal effects of 25 predominantly metabolic traits on liver iron content. Third, we tested phenome-wide associations between liver iron variants and 770 traits and disease outcomes. Results: We identified 3 independent genetic variants (rs1800562 [C282Y] and rs1799945 [H63D] in HFE and rs855791 [V736A] in TMPRSS6) associated with liver iron content that reached the GWAS significance threshold (p <5 × 10−8). The 2 HFE variants account for ∼85% of all cases of hereditary haemochromatosis. Mendelian randomisation analysis provided evidence that higher central obesity plays a causal role in increased liver iron content. Phenome-wide association analysis demonstrated shared aetiopathogenic mechanisms for elevated liver iron, high blood pressure, cirrhosis, malignancies, neuropsychiatric and rheumatological conditions, while also highlighting inverse associations with anaemias, lipidaemias and ischaemic heart disease. Conclusion: Our study provides genetic evidence that mechanisms underlying higher liver iron content are likely systemic rather than organ specific, that higher central obesity is causally associated with higher liver iron, and that liver iron shares common aetiology with multiple metabolic and non-metabolic diseases. Lay summary: Excess liver iron content is common and is associated with liver diseases and metabolic diseases including diabetes, high blood pressure, and heart disease. We identified 3 genetic variants that are linked to an increased risk of developing higher liver iron content. We show that the same genetic variants are linked to higher risk of many diseases, but they may also be associated with some health advantages. Finally, we use genetic variants associated with waist-to-hip ratio as a tool to show that central obesity is causally associated with increased liver iron content.
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- Jung, Christian, et al.
(författare)
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A comparison of very old patients admitted to intensive care unit after acute versus elective surgery or intervention
- 2019
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Ingår i: Journal of critical care. - : W B SAUNDERS CO-ELSEVIER INC. - 0883-9441 .- 1557-8615. ; 52, s. 141-148
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Tidskriftsartikel (refereegranskat)abstract
- Background: We aimed to evaluate differences in outcome between patients admitted to intensive care unit (ICU) after elective versus acute surgery in a multinational cohort of very old patients (80 years; VIP). Predictors of mortality, with special emphasis on frailty, were assessed.Methods: In total, 5063 VIPs were induded in this analysis, 922 were admitted after elective surgery or intervention, 4141 acutely, with 402 after acute surgery. Differences were calculated using Mann-Whitney-U test and Wilcoxon test. Univariate and multivariable logistic regression were used to assess associations with mortality.Results: Compared patients admitted after acute surgery, patients admitted after elective surgery suffered less often from frailty as defined as CFS (28% vs 46%; p < 0.001), evidenced lower SOFA scores (4 +/- 5 vs 7 +/- 7; p < 0.001). Presence of frailty (CFS >4) was associated with significantly increased mortality both in elective surgery patients (7% vs 12%; p = 0.01), in acute surgery (7% vs 12%; p = 0.02).Conclusions: VIPs admitted to ICU after elective surgery evidenced favorable outcome over patients after acute surgery even after correction for relevant confounders. Frailty might be used to guide clinicians in risk stratification in both patients admitted after elective and acute surgery.
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- Cnossen, Maryse C., et al.
(författare)
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Variation in monitoring and treatment policies for intracranial hypertension in traumatic brain injury : a survey in 66 neurotrauma centers participating in the CENTER-TBI study
- 2017
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Ingår i: Critical Care. - : Springer. - 1364-8535 .- 1466-609X. ; 21:1
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: No definitive evidence exists on how intracranial hypertension should be treated in patients with traumatic brain injury (TBI). It is therefore likely that centers and practitioners individually balance potential benefits and risks of different intracranial pressure (ICP) management strategies, resulting in practice variation. The aim of this study was to examine variation in monitoring and treatment policies for intracranial hypertension in patients with TBI.METHODS: A 29-item survey on ICP monitoring and treatment was developed on the basis of literature and expert opinion, and it was pilot-tested in 16 centers. The questionnaire was sent to 68 neurotrauma centers participating in the Collaborative European Neurotrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI) study.RESULTS: The survey was completed by 66 centers (97% response rate). Centers were mainly academic hospitals (n = 60, 91%) and designated level I trauma centers (n = 44, 67%). The Brain Trauma Foundation guidelines were used in 49 (74%) centers. Approximately 90% of the participants (n = 58) indicated placing an ICP monitor in patients with severe TBI and computed tomographic abnormalities. There was no consensus on other indications or on peri-insertion precautions. We found wide variation in the use of first- and second-tier treatments for elevated ICP. Approximately half of the centers were classified as using a relatively aggressive approach to ICP monitoring and treatment (n = 32, 48%), whereas the others were considered more conservative (n = 34, 52%).CONCLUSIONS: Substantial variation was found regarding monitoring and treatment policies in patients with TBI and intracranial hypertension. The results of this survey indicate a lack of consensus between European neurotrauma centers and provide an opportunity and necessity for comparative effectiveness research.
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- Huijben, Jilske A., et al.
(författare)
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Variation in Blood Transfusion and Coagulation Management in Traumatic Brain Injury at the Intensive Care Unit : A Survey in 66 Neurotrauma Centers Participating in the Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury Study
- 2017
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Ingår i: Journal of Neurotrauma. - : Mary Ann Liebert. - 0897-7151 .- 1557-9042. ; 35:2, s. 323-332
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Tidskriftsartikel (refereegranskat)abstract
- Our aim was to describe current approaches and to quantify variability between European intensive care units (ICUs) in patients with traumatic brain injury (TBI). Therefore, we conducted a provider profiling survey as part of the Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI) study. The ICU Questionnaire was sent to 68 centers from 20 countries across Europe and Israel. For this study, we used ICU questions focused on 1) hemoglobin target level (Hb-TL), 2) coagulation management, and 3) deep venous thromboembolism (DVT) prophylaxis. Seventy-eight participants, mostly intensivists and neurosurgeons of 66 centers, completed the ICU questionnaire. For ICU-patients, half of the centers (N = 34; 52%) had a defined Hb-TL in their protocol. For patients with TBI, 26 centers (41%) indicated an Hb-TL between 70 and 90 g/L and 38 centers (59%) above 90 g/L. To treat trauma-related hemostatic abnormalities, the use of fresh frozen plasma (N = 48; 73%) or platelets (N = 34; 52%) was most often reported, followed by the supplementation of vitamin K (N = 26; 39%). Most centers reported using DVT prophylaxis with anticoagulants frequently or always (N = 62; 94%). In the absence of hemorrhagic brain lesions, 14 centers (21%) delayed DVT prophylaxis until 72 h after trauma. If hemorrhagic brain lesions were present, the number of centers delaying DVT prophylaxis for 72 h increased to 29 (46%). Overall, a lack of consensus exists between European ICUs on blood transfusion and coagulation management. The results provide a baseline for the CENTER-TBI study, and the large between-center variation indicates multiple opportunities for comparative effectiveness research.
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- Malmborg, Julia S, 1988-, et al.
(författare)
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Worse health status, sleeping problems, and anxiety in 16-year-old students are associated with chronic musculoskeletal pain at three-year follow-up
- 2019
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Ingår i: BMC Public Health. - London : Springer Science and Business Media LLC. - 1471-2458. ; 19:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: Chronic musculoskeletal pain is common in adolescents, and it has been shown that adolescents with pain may become young adults with pain. Pain often coincides with psychosomatic symptoms in adults, but little is known about longitudinal associations and predictors of pain in adolescents. The aim was to investigate chronic musculoskeletal pain and its associations with health status, sleeping problems, stress, anxiety, depression, and physical activity in 16-year-old students at baseline, and to identify risk factors using a three-year follow-up. Methods: This was a longitudinal study of 256 students attending a Swedish upper secondary school. Questionnaires regarding chronic musculoskeletal pain and distribution of pain (mannequin), health status (EQ-5D3 L), sleeping problems (Uppsala Sleep Inventory), stress symptoms (single-item question), anxiety and depression (Hospital Anxiety and Depression Scale), and physical activity (International Physical Activity Questionnaire) were issued at baseline and follow-up. Student's t-test and chi2 test were used for descriptive statistics and logistic regression analyses were used to study associations between chronic pain and independent variables. Results: Fifty-two out of 221 students at baseline (23.5%) and 39 out of 154 students at follow-up (25.3%) were categorized as having chronic musculoskeletal pain. Chronic musculoskeletal pain at follow-up was separately associated with reporting of an EQ-5D value below median (OR 4.06, 95% CI 1.83-9.01), severe sleeping problems (OR 3.63, 95% CI 1.69-7.82), and possible anxiety (OR 4.19, 95% CI 1.74-10.11) or probable anxiety (OR 3.82, 95% CI 1.17-12.48) at baseline. Similar results were found for associations between chronic musculoskeletal pain and independent variables at baseline. In multiple logistic regression analysis, chronic musculoskeletal pain at baseline was a predictor of chronic musculoskeletal pain at follow-up (OR 2.99, 95% CI 1.09-8.24, R-2 = 0.240). Conclusion: Chronic musculoskeletal pain at baseline was the most important predictor for reporting chronic musculoskeletal pain at the three-year follow-up, but a worse health status, severe sleeping problems, and anxiety also predicted persistence or development of chronic musculoskeletal pain over time. Interventions should be introduced early on by the school health services to promote student health.
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| 8. |
- Huijben, Jilske A., et al.
(författare)
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Variation in general supportive and preventive intensive care management of traumatic brain injury : a survey in 66 neurotrauma centers participating in the Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI) study
- 2018
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Ingår i: Critical Care. - : Springer. - 1364-8535 .- 1466-609X. ; 22:1
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: General supportive and preventive measures in the intensive care management of traumatic brain injury (TBI) aim to prevent or limit secondary brain injury and optimize recovery. The aim of this survey was to assess and quantify variation in perceptions on intensive care unit (ICU) management of patients with TBI in European neurotrauma centers.METHODS: We performed a survey as part of the Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI) study. We analyzed 23 questions focused on: 1) circulatory and respiratory management; 2) fever control; 3) use of corticosteroids; 4) nutrition and glucose management; and 5) seizure prophylaxis and treatment.RESULTS: The survey was completed predominantly by intensivists (n = 33, 50%) and neurosurgeons (n = 23, 35%) from 66 centers (97% response rate). The most common cerebral perfusion pressure (CPP) target was > 60 mmHg (n = 39, 60%) and/or an individualized target (n = 25, 38%). To support CPP, crystalloid fluid loading (n = 60, 91%) was generally preferred over albumin (n = 15, 23%), and vasopressors (n = 63, 96%) over inotropes (n = 29, 44%). The most commonly reported target of partial pressure of carbon dioxide in arterial blood (PaCO2) was 36-40 mmHg (4.8-5.3 kPa) in case of controlled intracranial pressure (ICP) < 20 mmHg (n = 45, 69%) and PaCO2 target of 30-35 mmHg (4-4.7 kPa) in case of raised ICP (n = 40, 62%). Almost all respondents indicated to generally treat fever (n = 65, 98%) with paracetamol (n = 61, 92%) and/or external cooling (n = 49, 74%). Conventional glucose management (n = 43, 66%) was preferred over tight glycemic control (n = 18, 28%). More than half of the respondents indicated to aim for full caloric replacement within 7 days (n = 43, 66%) using enteral nutrition (n = 60, 92%). Indications for and duration of seizure prophylaxis varied, and levetiracetam was mostly reported as the agent of choice for both seizure prophylaxis (n = 32, 49%) and treatment (n = 40, 61%).CONCLUSIONS: Practice preferences vary substantially regarding general supportive and preventive measures in TBI patients at ICUs of European neurotrauma centers. These results provide an opportunity for future comparative effectiveness research, since a more evidence-based uniformity in good practices in general ICU management could have a major impact on TBI outcome.
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| 9. |
- Malmborg, Julia, 1988-, et al.
(författare)
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Sleeping Problems and Anxiety is Associated to Chronic Multisite Musculoskeletal Pain in Swedish High School Students
- 2018
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Ingår i: Annals of the Rheumatic Diseases. - London : BMJ Publishing Group Ltd. - 0003-4967 .- 1468-2060. ; 77:Suppl. 2, s. 226-226
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Background: The relationship between chronic multisite musculoskeletal pain (CMP) and sleep is complex, where pain can lead to sleeping problems and lack of sleep can intensify the pain perception. Most previous studies relates to adults, but adolescents may also suffer from CMP, and there is a need for more knowledge regarding the relationships between CMP and sleeping problems, stress, anxiety, depression, and health status.Objectives: To study background factors associated to CMP in first year Swedish high school students.Methods: First year Swedish high school students (n=296) were invited to complete questionnaires on chronic pain (mannequin with 18 body regions), sleeping problems (Uppsala Sleep Inventory, four items scored from 1–5), stress (ELO questions, scored from 1–5), anxiety and depression (Hospital Anxiety and Depression Scale, scored from 0–21), health status (EQ-5D, scored from 0 to 1, worst to best) and physical activity (International Physical Activity Questionnaire, categorised into low, moderate and high levels). Stress and sleeping items were dichotomized into 1–3 points (best) vs 4–5 points (worst). Individuals scoring at least severe problems (4 points) at one or more sleeping items were classified as having severe sleeping problems. HADS were categorised as non-cases (0–7), possible7–10 and probable cases (11–21 points). Students were grouped as having CMP (pain present in ≥3 regions) or not (no chronic pain or chronic pain in 1–2 regions). Multiple logistic regression analyses (adjusted for sex) with CMP as dependent variable were performed in SPSS, version 24.Results: 254 students (86% of total sample, 87 boys and 167 girls) with a mean age of 16.1 (SD 0.6) years participated in the study. CMP was present in 25 (9.8%) students with no differences between boys and girls (8.0% vs 10.8%; p=0.488). Having CMP was associated with reporting severe sleeping problems (OR 2.49, 95% CI: 1.06 to 5.81, p=0.035) with initiating sleep, maintaining sleep, early morning awakenings and/or not feeling restored after sleep in comparison to the other students. Students with CMP were more likely to be categorised as probable cases for anxiety (OR 3.06, 95% CI: 1.09 to 8.61, p=0.034), but there were no associations for possible cases for anxiety (OR 1.15, 95% CI: 0.38 to 3.51, p=0.800), possible cases (OR 2.03, 95% CI: 0.63 to 6.54), or probable cases for depression (OR 3.35, 95% CI: 0.33 to 33.83). There was a nearly significant association between stress and belonging to the CMP group (OR 2.31, 95% CI: 0.97 to 5.53, p=0.059). A higher self-reported health status was associated to a lower likelihood for CMP (OR 0.04, 95% CI: 0.01 to 0.27, p=0.001). Distribution of physical activity levels of low, moderate and high was not significantly associated to having CMP in comparison with not having it.Conclusions: One in ten high school students fulfilled criteria for having chronic multisite musculoskeletal pain. CMP was associated to sleeping problems, anxiety, and a worse health status. The results from this study may be used by school health-care professionals in their preventive work to promote student’s health.Disclosure of Interest: None declared
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