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1.	Semb, Gunvor, et al. (author) A Scandcleft randomised trials of primary surgery for unilateral cleft lip and palate: 1. Planning and management. 2017 In: Journal of Plastic Surgery and Hand Surgery. - : Taylor & Francis. - 2000-656X .- 2000-6764. ; 51:1, s. 2-13 Journal article (peer-reviewed)abstract BACKGROUND AND AIMS: Longstanding uncertainty surrounds the selection of surgical protocols for the closure of unilateral cleft lip and palate, and randomised trials have only rarely been performed. This paper is an introduction to three randomised trials of primary surgery for children born with complete unilateral cleft lip and palate (UCLP). It presents the protocol developed for the trials in CONSORT format, and describes the management structure that was developed to achieve the long-term engagement and commitment required to complete the project.METHOD: Ten established national or regional cleft centres participated. Lip and soft palate closure at 3-4 months, and hard palate closure at 12 months served as a common method in each trial. Trial 1 compared this with hard palate closure at 36 months. Trial 2 compared it with lip closure at 3-4 months and hard and soft palate closure at 12 months. Trial 3 compared it with lip and hard palate closure at 3-4 months and soft palate closure at 12 months. The primary outcomes were speech and dentofacial development, with a series of perioperative and longer-term secondary outcomes.RESULTS: Recruitment of 448 infants took place over a 9-year period, with 99.8% subsequent retention at 5 years.CONCLUSION: The series of reports that follow this introductory paper include comparisons at age 5 of surgical outcomes, speech outcomes, measures of dentofacial development and appearance, and parental satisfaction. The outcomes recorded and the numbers analysed for each outcome and time point are described in the series.TRIAL REGISTRATION: ISRCTN29932826.
2.	Abarkan, Abdellah, et al. (author) Corona hotar förvärra svenska bostadskrisen. 108 forskare: Sveriges regering och kommuner måste förhindra en katastrof. 2020 In: Aftonbladet. - 1103-9000. Journal article (pop. science, debate, etc.)abstract Debattartikel och Öppet brev publicerad i tidningen Aftonbladet. 29.3. 2020.
3.	Andersen, Christina, et al. (author) Atmospheric Chemistry of Tetrahydrofuran, 2-Methyltetrahydrofuran, and 2,5-Dimethyltetrahydrofuran : Kinetics of Reactions with Chlorine Atoms, OD Radicals, and Ozone 2016 In: The Journal of Physical Chemistry Part A: Molecules, Spectroscopy, Kinetics, Environment and General Theory. - : American Chemical Society (ACS). - 1089-5639. ; 120:37, s. 7320-7326 Journal article (peer-reviewed)abstract FTIR smog chamber techniques were used to study the kinetics of the gas-phase reactions of Cl atoms, OD radicals, and O3 with the five-membered ring-structured compounds tetrahydrofuran (C4H8O, THF), 2-methyltetrahydrofuran (CH3C4H7O, 2-MTHF), 2,5-dimethyltetrahydrofuran ((CH3)2C4H5O, 2,5-DMTHF), and furan (C4H4O). The rate coefficients determined using relative rate methods were kTHF+Cl = (1.96 ± 0.24) × 10-10, kTHF+OD = (1.81 ± 0.27) × 10-11, kTHF+O3 = (6.41 ± 2.90) × 10-21, k2-MTHF+Cl = (2.65 ± 0.43) × 10-10, k2-MTHF+OD = (2.41 ± 0.51) × 10-11, k2-MTHF+O3 = (1.87 ± 0.82) × 10-20, k2,5-DMTHF+OD = (4.56 ± 0.68) × 10-11, k2,5-DMTHF+Cl = (2.84 ± 0.34) × 10-10, k2,5-DMTHF+O3 = (4.58 ± 2.18), kfuran+Cl = (2.39 ± 0.27) × 10-10, and kfuran+O3 = (2.60 ± 0.31) × 10-18 molecules cm-3 s-1. Rate coefficients of the reactions with ozone were also determined using the absolute rate method under pseudo-first-order conditions. OD radicals, in place of OH radicals, were produced from CD3ONO to avoid spectral overlap of isopropyl and methyl nitrite with the reactants. The kinetics of OD radical reactions are expected to resemble the kinetics of OH radical reactions, and the rate coefficients of the reactions with OD radicals were used to calculate the atmospheric lifetimes with respect to reactions with OH radicals. The lifetimes of THF, 2-MTHF, and 2,5-DMTHF are approximately 15, 12, and 6 h, respectively.
4.	Brieghel, Christian, et al. (author) The Number of Signaling Pathways Altered by Driver Mutations in Chronic Lymphocytic Leukemia Impacts Disease Outcome 2020 In: Clinical Cancer Research. - : AMER ASSOC CANCER RESEARCH. - 1078-0432 .- 1557-3265. ; 26:6, s. 1507-1515 Journal article (peer-reviewed)abstract Purpose: Investigation of signaling pathways altered by recurrent gene mutations and their clinical impact in a consecutive cohort of patients with newly diagnosed chronic lymphocytic leukemia (CLL). The heterogeneous clinical course and genetic complexity of CLL warrant improved molecular prognostication. However, the prognostic value of recurrent mutations at the time of diagnosis remains unclear. Experimental Design: We sequenced samples from 314 consecutive, newly diagnosed patients with CLL to investigate the clinical impact of 56 recurrently mutated genes assessed by next-generation sequencing. Results: Mutations were identified in 70% of patients with enrichment among IGHV unmutated cases. With 6.5 years of follow-up, 15 mutated genes investigated at the time of diagnosis demonstrated significant impact on time to first treatment (TTFT). Carrying driver mutations was associated with shorter TTFT and poor overall survival. For outcome from CLL diagnosis, the number of signaling pathways altered by driver mutations stratified patients better than the number of driver mutations. Moreover, we demonstrated gradual impact on TTFT with increasing number of altered pathways independent of CLL-IPI risk. Thus, a 25-gene, pathway-based biomarker assessing recurrent mutations refines prognostication in CLL, in particular for CLL-IPI low- and intermediate-risk patients. External validation emphasized that a broad gene panel including low burden mutations was key for the biomarker based on altered pathways. Conclusions: We propose to include the number of pathways altered by driver mutations as a biomarker together with CLL-IPI in prospective studies of CLL from time of diagnosis for incorporation into clinical care and personalized follow-up and treatment.
5.	Gamble, Carrol, et al. (author) Timing of Primary Surgery for Cleft Palate. 2023 In: The New England journal of medicine. - : Massachusetts Medical Society. - 1533-4406 .- 0028-4793. ; 389:9, s. 795-807 Journal article (peer-reviewed)abstract Among infants with isolated cleft palate, whether primary surgery at 6 months of age is more beneficial than surgery at 12 months of age with respect to speech outcomes, hearing outcomes, dentofacial development, and safety is unknown.We randomly assigned infants with nonsyndromic isolated cleft palate, in a 1:1 ratio, to undergo standardized primary surgery at 6 months of age (6-month group) or at 12 months of age (12-month group) for closure of the cleft. Standardized assessments of quality-checked video and audio recordings at 1, 3, and 5 years of age were performed independently by speech and language therapists who were unaware of the trial-group assignments. The primary outcome was velopharyngeal insufficiency at 5 years of age, defined as a velopharyngeal composite summary score of at least 4 (scores range from 0 to 6, with higher scores indicating greater severity). Secondary outcomes included speech development, postoperative complications, hearing sensitivity, dentofacial development, and growth.We randomly assigned 558 infants at 23 centers across Europe and South America to undergo surgery at 6 months of age (281 infants) or at 12 months of age (277 infants). Speech recordings from 235 infants (83.6%) in the 6-month group and 226 (81.6%) in the 12-month group were analyzable. Insufficient velopharyngeal function at 5 years of age was observed in 21 of 235 infants (8.9%) in the 6-month group as compared with 34 of 226 (15.0%) in the 12-month group (risk ratio, 0.59; 95% confidence interval, 0.36 to 0.99; P=0.04). Postoperative complications were infrequent and similar in the 6-month and 12-month groups. Four serious adverse events were reported (three in the 6-month group and one in the 12-month group) and had resolved at follow-up.Medically fit infants who underwent primary surgery for isolated cleft palate in adequately resourced settings at 6 months of age were less likely to have velopharyngeal insufficiency at the age of 5 years than those who had surgery at 12 months of age. (Funded by the National Institute of Dental and Craniofacial Research; TOPS ClinicalTrials.gov number, NCT00993551.).
6.	Lohmander, Anette, et al. (author) Scandcleft randomised trials of primary surgery for unilateral cleft lip and palate: 4. Speech outcomes in 5-year-olds - velopharyngeal competency and hypernasality 2017 In: Journal of Plastic Surgery and Hand Surgery. - : TAYLOR & FRANCIS LTD. - 2000-656X .- 2000-6764. ; 51:1, s. 27-37 Journal article (peer-reviewed)abstract Background and aim: Adequate velopharyngeal function and speech are main goals in the treatment of cleft palate. The objective was to investigate if there were differences in velopharyngeal competency (VPC) and hypernasality at age 5 years in children with unilateral cleft lip and palate (UCLP) operated on with different surgical methods for primary palatal repair. A secondary aim was to estimate burden of care in terms of received additional secondary surgeries and speech therapy. Design: Three parallel group, randomised clinical trials were undertaken as an international multicentre study by 10 cleft teams in five countries: Denmark, Finland, Sweden, Norway, and the UK. Methods: Three different surgical protocols for primary palatal repair were tested against a common procedure in the total cohort of 448 children born with a non-syndromic UCLP. Speech audio and video recordings of 391 children (136 girls, 255 boys) were available and perceptually analysed. The main outcome measures were VPC and hypernasality from blinded assessments. Results: There were no statistically significant differences between the prevalences in the arms in any of the trials. VPC: Trial 1, A: 58%, B: 61%; Trial 2, A: 57%, C: 54%; Trial 3, A: 35%, D: 51%. No hypernasality: Trial 1, A: 54%, B: 44%; Trial 2, A: 47%, C: 51%; Trial 3, A: 34%, D: 49%. Conclusions: No differences were found regarding VPC and hypernasality at age 5 years after different methods for primary palatal repair. The burden of care in terms of secondary pharyngeal surgeries, number of fistulae, and speech therapy visits differed.
7.	Rasmussen, Maria, et al. (author) Lynch syndrome-associated epithelial ovarian cancer and its immunological profile 2021 In: Gynecologic Oncology. - : Elsevier BV. - 0090-8258. ; 162:3, s. 686-693 Journal article (peer-reviewed)abstract Introduction: Lynch syndrome is a multi-tumor syndrome characterized by mismatch repair deficiency (MMR-d), microsatellite instability (MSI), and increased tumor-infiltrating lymphocytes (TILs) making these tumors candidates for treatment with immune checkpoint inhibitors. However, response may depend on tumor-induced immune evasion mechanisms, e.g. loss of Beta-2-Microglobulin (B2M) or upregulation of programmed death protein ligand 1 (PD-L1). We investigated the immune response and B2M and PD-L1 expression in Lynch syndrome-associated ovarian cancers. Methods: We successfully analyzed 30 Lynch syndrome-associated epithelial ovarian cancers collected through the Danish Hereditary Non-Polyposis Colorectal Cancer (HNPCC) register. MMR-d, MSI, immune response (CD3, CD8, and CD68), and immune evasion mechanisms (B2M and PD-L1) were investigated. Statistical associations between these markers were evaluated in addition to survival in relation to B2M/PD-L1. Results: Of the 29 evaluable tumors, 27 were MMR-d (93.1%). Likewise of 26 evaluable tumors, 14 were MSI (53.8%). MMR-d/MMR-proficiency associated with MSI/MSS in 60.0%. Half of the ovarian tumors presented with high levels of TILs. Loss of B2M expression was observed in 46.7% of the tumors, while expression of PD-L1 was seen in 28.0% of the cases. There was no association between B2M/PD-L1 and MSI/TILs/survival. Loss of B2M was often seen in tumors with low TILs (p = 0.056 or p = 0.059 for CD3 and CD8 positive cells, respectively). Conclusion: MMR-d, MSI, and TILs are also seen in Lynch syndrome-associated ovarian cancers making these potential candidates for checkpoint-based immunotherapy. The clinical impact from immune evasion through loss of B2M needs to be investigated further in larger cohorts.
8.	Schunkert, Heribert, et al. (author) Large-scale association analysis identifies 13 new susceptibility loci for coronary artery disease 2011 In: Nature Genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 43:4, s. 153-333 Journal article (peer-reviewed)abstract We performed a meta-analysis of 14 genome-wide association studies of coronary artery disease (CAD) comprising 22,233 individuals with CAD (cases) and 64,762 controls of European descent followed by genotyping of top association signals in 56,682 additional individuals. This analysis identified 13 loci newly associated with CAD at P < 5 x 10(-8) and confirmed the association of 10 of 12 previously reported CAD loci. The 13 new loci showed risk allele frequencies ranging from 0.13 to 0.91 and were associated with a 6% to 17% increase in the risk of CAD per allele. Notably, only three of the new loci showed significant association with traditional CAD risk factors and the majority lie in gene regions not previously implicated in the pathogenesis of CAD. Finally, five of the new CAD risk loci appear to have pleiotropic effects, showing strong association with various other human diseases or traits.
9.	Walkowska, Joanna, et al. (author) Immunoprofiles of colorectal cancer from Lynch syndrome 2019 In: OncoImmunology. - 2162-4011. ; 8:1 Journal article (peer-reviewed)abstract Colorectal cancers associated with Lynch syndrome are characterized by defective mismatch repair, microsatellite instability, high mutation rates, and a highly immunogenic environment. These features define a subset of cancer with a favorable prognosis and high likelihood to respond to treatment with anti-programmed death 1 (PD-1)/programmed death ligand 1 (PD-L1) drugs. With the aim to define immune-evasive mechanisms and a potential impact hereof in colorectal cancers from Lynch syndrome versus hereditary cases with retained mismatch repair function, we immunohistochemically and transcriptionally profiled 270 tumors. Lynch syndrome-associated tumors showed an overrepresentation of tumor-infiltrating CD3, CD8 and CD68 positive cells, loss of beta-2-microglobulin (B2M) and up-regulation of PD-L1 on tumor cells. The gene expression signature of Lynch syndrome tumors was characterized by upregulation of genes related to antigen processing and presentation, apoptosis, natural killer cell-mediated cytotoxicity, and T cell activation. Tumors with loss of B2M and up-regulation of PD-L1 showed distinctive immunogenic profiles. In summary, our data demonstrate a complex tumor-host interplay where B2M loss and PD-L1 up-regulation influence immunological pathways and clinical outcome in Lynch syndrome tumors. Immunological classification may thus aid in the preselection of colorectal cancers relevant for treatment with anti-PD-1/PD-L1 therapies.
10.	Wang, Haidong, et al. (author) Global, regional, and national life expectancy, all-cause mortality, and cause-specific mortality for 249 causes of death, 1980-2015 : a systematic analysis for the Global Burden of Disease Study 2015 2016 In: The Lancet. - 0140-6736 .- 1474-547X. ; 388:10053, s. 1459-1544 Journal article (peer-reviewed)abstract BACKGROUND: Improving survival and extending the longevity of life for all populations requires timely, robust evidence on local mortality levels and trends. The Global Burden of Disease 2015 Study (GBD 2015) provides a comprehensive assessment of all-cause and cause-specific mortality for 249 causes in 195 countries and territories from 1980 to 2015. These results informed an in-depth investigation of observed and expected mortality patterns based on sociodemographic measures.METHODS: We estimated all-cause mortality by age, sex, geography, and year using an improved analytical approach originally developed for GBD 2013 and GBD 2010. Improvements included refinements to the estimation of child and adult mortality and corresponding uncertainty, parameter selection for under-5 mortality synthesis by spatiotemporal Gaussian process regression, and sibling history data processing. We also expanded the database of vital registration, survey, and census data to 14 294 geography-year datapoints. For GBD 2015, eight causes, including Ebola virus disease, were added to the previous GBD cause list for mortality. We used six modelling approaches to assess cause-specific mortality, with the Cause of Death Ensemble Model (CODEm) generating estimates for most causes. We used a series of novel analyses to systematically quantify the drivers of trends in mortality across geographies. First, we assessed observed and expected levels and trends of cause-specific mortality as they relate to the Socio-demographic Index (SDI), a summary indicator derived from measures of income per capita, educational attainment, and fertility. Second, we examined factors affecting total mortality patterns through a series of counterfactual scenarios, testing the magnitude by which population growth, population age structures, and epidemiological changes contributed to shifts in mortality. Finally, we attributed changes in life expectancy to changes in cause of death. We documented each step of the GBD 2015 estimation processes, as well as data sources, in accordance with Guidelines for Accurate and Transparent Health Estimates Reporting (GATHER).FINDINGS: Globally, life expectancy from birth increased from 61·7 years (95% uncertainty interval 61·4-61·9) in 1980 to 71·8 years (71·5-72·2) in 2015. Several countries in sub-Saharan Africa had very large gains in life expectancy from 2005 to 2015, rebounding from an era of exceedingly high loss of life due to HIV/AIDS. At the same time, many geographies saw life expectancy stagnate or decline, particularly for men and in countries with rising mortality from war or interpersonal violence. From 2005 to 2015, male life expectancy in Syria dropped by 11·3 years (3·7-17·4), to 62·6 years (56·5-70·2). Total deaths increased by 4·1% (2·6-5·6) from 2005 to 2015, rising to 55·8 million (54·9 million to 56·6 million) in 2015, but age-standardised death rates fell by 17·0% (15·8-18·1) during this time, underscoring changes in population growth and shifts in global age structures. The result was similar for non-communicable diseases (NCDs), with total deaths from these causes increasing by 14·1% (12·6-16·0) to 39·8 million (39·2 million to 40·5 million) in 2015, whereas age-standardised rates decreased by 13·1% (11·9-14·3). Globally, this mortality pattern emerged for several NCDs, including several types of cancer, ischaemic heart disease, cirrhosis, and Alzheimer's disease and other dementias. By contrast, both total deaths and age-standardised death rates due to communicable, maternal, neonatal, and nutritional conditions significantly declined from 2005 to 2015, gains largely attributable to decreases in mortality rates due to HIV/AIDS (42·1%, 39·1-44·6), malaria (43·1%, 34·7-51·8), neonatal preterm birth complications (29·8%, 24·8-34·9), and maternal disorders (29·1%, 19·3-37·1). Progress was slower for several causes, such as lower respiratory infections and nutritional deficiencies, whereas deaths increased for others, including dengue and drug use disorders. Age-standardised death rates due to injuries significantly declined from 2005 to 2015, yet interpersonal violence and war claimed increasingly more lives in some regions, particularly in the Middle East. In 2015, rotaviral enteritis (rotavirus) was the leading cause of under-5 deaths due to diarrhoea (146 000 deaths, 118 000-183 000) and pneumococcal pneumonia was the leading cause of under-5 deaths due to lower respiratory infections (393 000 deaths, 228 000-532 000), although pathogen-specific mortality varied by region. Globally, the effects of population growth, ageing, and changes in age-standardised death rates substantially differed by cause. Our analyses on the expected associations between cause-specific mortality and SDI show the regular shifts in cause of death composition and population age structure with rising SDI. Country patterns of premature mortality (measured as years of life lost [YLLs]) and how they differ from the level expected on the basis of SDI alone revealed distinct but highly heterogeneous patterns by region and country or territory. Ischaemic heart disease, stroke, and diabetes were among the leading causes of YLLs in most regions, but in many cases, intraregional results sharply diverged for ratios of observed and expected YLLs based on SDI. Communicable, maternal, neonatal, and nutritional diseases caused the most YLLs throughout sub-Saharan Africa, with observed YLLs far exceeding expected YLLs for countries in which malaria or HIV/AIDS remained the leading causes of early death.INTERPRETATION: At the global scale, age-specific mortality has steadily improved over the past 35 years; this pattern of general progress continued in the past decade. Progress has been faster in most countries than expected on the basis of development measured by the SDI. Against this background of progress, some countries have seen falls in life expectancy, and age-standardised death rates for some causes are increasing. Despite progress in reducing age-standardised death rates, population growth and ageing mean that the number of deaths from most non-communicable causes are increasing in most countries, putting increased demands on health systems.
11.	Willadsen, Elisabeth, et al. (author) Scandcleft Project, Trial 1: Comparison of Speech Outcome in Relation to Timing of Hard Palate Closure in 5-Year-Olds With UCLP. 2019 In: The Cleft palate-craniofacial journal : official publication of the American Cleft Palate-Craniofacial Association. - : SAGE Publications. - 1545-1569. ; 56:10, s. 1276-1286 Journal article (peer-reviewed)abstract To compare in-depth speech results in Scandcleft Trial 1 as well as reference data from peers without cleft palate (CP).A prospective randomized clinical trial.A Danish and a Swedish CP center.143 of 148 randomized 5-year-olds with unilateral cleft lip and palate. All received lip and velum closure at 4 months, and hard palate closure at 12 months (arm A) or 36 months (arm B).A composite measure based on velopharyngeal competence (VPC) or velopharyngeal incompetence (VPI), an overall assessment of VPC from connected speech (VPC-Rate), Percentage of Consonants Correct (PCC-score), and consonant errors. Speech therapy visits, average hearing thresholds, and secondary pharyngeal surgeries documented burden of treatment.Across the trial, 61.5% demonstrated VPC and 38.5% VPI. Twenty-two percent of participants achieved age appropriate PCC-scores. There were no statistically significant differences between arms or centers for these measures. In the Danish center, arm B: achieved lower PCC-scores (P = .01); obtained PCC-scores without s-errors below 79% (P = .002); produced ≥3 active oral cleft speech characteristics (P = .004) than arm A. In both centers, arm B attended more speech visits.At age 5, differences between centers and treatment arms were not statistically significant for VPC/VPI, but consonant proficiency differed between treatment arms in the Danish center. Poor speech outcomes were seen for both treatment arms. Variations between centers were observed. As the Swedish center had few participants, intercenter comparisons should be interpreted with caution.
12.	Willadsen, Elisabeth, et al. (author) Scandcleft randomised trials of primary surgery for unilateral cleft lip and palate: 5. Speech outcomes in 5-year-olds - consonant proficiency and errors 2017 In: Journal of Plastic Surgery and Hand Surgery. - : TAYLOR & FRANCIS LTD. - 2000-656X .- 2000-6764. ; 51:1, s. 38-51 Journal article (peer-reviewed)abstract Background and aim: Normal articulation before school start is a main objective in cleft palate treatment. The aim was to investigate if differences exist in consonant proficiency at age 5 years between children with unilateral cleft lip and palate (UCLP) randomised to different surgical protocols for primary palatal repair. A secondary aim was to estimate burden of care in terms of received additional secondary surgeries and speech therapy. Design: Three parallel group, randomised clinical trials were undertaken as an international multicentre study by 10 cleft teams in five countries: Denmark, Finland, Norway, Sweden, and the UK. Methods: Three different surgical protocols for primary palatal repair were tested against a common procedure in the total cohort of 448 children born with non-syndromic UCLP. Speech audio- and video-recordings of 391 children (136 girls and 255 boys) were available and transcribed phonetically. The main outcome measure was Percent Consonants Correct (PCC) from blinded assessments. Results: In Trial 1, arm A showed statistically significant higher PCC scores (82%) than arm B (78%) (p=.045). No significant differences were found between prevalences in Trial 2, A: 79%, C: 82%; or Trial 3, A: 80%, D: 85%. Across all trials, girls achieved better PCC scores, excluding s-errors, than boys (91.0% and 87.5%, respectively) (p=.01). Conclusions: PCC scores were higher in arm A than B in Trial 1, whereas no differences were found between arms in Trials 2 or 3. The burden of care in terms of secondary pharyngeal surgeries, number of fistulae, and speech therapy visits differed.
13.	Willadsen, E., et al. (author) Scandcleft randomized trials of primary surgery for unilateral cleft lip and palate: Speech proficiency at 10 years of age 2023 In: International journal of language and communication disorders. - : WILEY. - 1368-2822 .- 1460-6984. ; 58:3, s. 892-909 Journal article (peer-reviewed)abstract Background & AimTo assess consonant proficiency and velopharyngeal function in 10-year-old children born with unilateral cleft lip and palate (UCLP) within the Scandcleft project. Methods & ProceduresThree parallel group, randomized, clinical trials were undertaken as an international multicentre study by nine cleft teams in five countries. Three different surgical protocols for primary palate repair (Arm B-Lip and soft palate closure at 3-4 months, hard palate closure at 36 months, Arm C-Lip closure at 3-4 months, hard and soft palate closure at 12 months, and Arm D-Lip closure at 3-4 months combined with a single-layer closure of the hard palate using a vomer flap, soft palate closure at 12 months) were tested against a common procedure (Arm A-Lip and soft palate closure at 3-4 months followed by hard palate closure at 12 months) in the total cohort of 431 children born with a non-syndromic UCLP. Speech audio and video recordings of 399 children were available and perceptually analysed. Percentage of consonants correct (PCC) from a naming test, an overall rating of velopharyngeal competence (VPC) (VPC-Rate), and a composite measure (VPC-Sum) were reported. Outcomes & ResultsThe mean levels of consonant proficiency (PCC score) in the trial arms were 86-92% and between 58% and 83% of the children had VPC (VPC-Sum). Only 50-73% of the participants had a consonant proficiency level with their peers. Girls performed better throughout. Long delay of the hard palate repair (Arm B) indicated lower PCC and simultaneous hard and soft palate closure higher (Arm C). However, the proportion of participants with primary VPC (not including velopharyngeal surgeries) was highest in Arm B (68%) and lowest in Arm C (47%). Conclusions & ImplicationsThe speech outcome in terms of PCC and VPC was low across the trials. The different protocols had their pros and cons and there is no obvious evidence to recommend any of the protocols as superior. Aspects other than primary surgical method, such as time after velopharyngeal surgery, surgical experience, hearing level, language difficulties and speech therapy, need to be thoroughly reviewed for a better understanding of what has affected speech outcome at 10 years. WHAT THIS PAPER ADDSWhat is already known on the subjectSpeech outcomes at 10 years of age in children treated for UCLP are sparse and contradictory. Previous studies have examined speech outcomes and the relationship with surgical intervention in 5-year-olds. What this study adds to the existing knowledgeSpeech outcomes based on standardized assessment in a large group of 10-year-old children born with UCLP and surgically treated according to different protocols are presented. While speech therapy had been provided, a large proportion of the children across treatment protocols still needed further speech therapy. What are the potential or actual clinical implications of this work?Aspects other than surgery and speech function might add to the understanding of what affects speech outcome. Effective speech therapy should be available for children in addition to primary surgical repair of the cleft and secondary surgeries if needed.
14.	2019 Journal article (peer-reviewed)
15.	Ahmed, Niaz, et al. (author) Consensus statements and recommendations from the ESO-Karolinska Stroke Update Conference, Stockholm 11-13 November 2018. 2019 In: European Stroke Journal. - : SAGE Publications. - 2396-9873 .- 2396-9881. ; 4:4, s. 307-317 Journal article (peer-reviewed)abstract The purpose of the European Stroke Organisation-Karolinska Stroke Update Conference is to provide updates on recent stroke therapy research and to give an opportunity for the participants to discuss how these results may be implemented into clinical routine. The meeting started 22 years ago as Karolinska Stroke Update, but since 2014 it is a joint conference with European Stroke Organisation. Importantly, it provides a platform for discussion on the European Stroke Organisation guidelines process and on recommendations to the European Stroke Organisation guidelines committee on specific topics. By this, it adds a direct influence from stroke professionals otherwise not involved in committees and work groups on the guideline procedure. The discussions at the conference may also inspire new guidelines when motivated. The topics raised at the meeting are selected by the scientific programme committee mainly based on recent important scientific publications. This year's European Stroke Organisation-Karolinska Stroke Update Meeting was held in Stockholm on 11-13 November 2018. There were 11 scientific sessions discussed in the meeting including two short sessions. Each session except the short sessions produced a consensus statement (Full version with background, issues, conclusions and references are published as web-material and at www.eso-karolinska.org and http://eso-stroke.org) and recommendations which were prepared by a writing committee consisting of session chair(s), scientific secretary and speakers. These statements were presented to the 250 participants of the meeting. In the open meeting, general participants commented on the consensus statement and recommendations and the final document were adjusted based on the discussion from the general participants Recommendations (grade of evidence) were graded according to the 1998 Karolinska Stroke Update meeting with regard to the strength of evidence. Grade A Evidence: Strong support from randomised controlled trials and statistical reviews (at least one randomised controlled trial plus one statistical review). Grade B Evidence: Support from randomised controlled trials and statistical reviews (one randomised controlled trial or one statistical review). Grade C Evidence: No reasonable support from randomised controlled trials, recommendations based on small randomised and/or non-randomised controlled trials evidence.
16.	Aldenius, Malin, et al. (author) “Mind the gap!” : Aiming high in collaborative group work 2017 In: Lärande i LTH. ; 37, s. 5-6 Journal article (pop. science, debate, etc.)
17.	Anand, Kanwlajeet J. S., et al. (author) Assessment of continuous pain in newborns admitted to NICUs in 18 European countries 2017 In: Acta Paediatrica. - : John Wiley & Sons. - 0803-5253 .- 1651-2227. ; 106:8, s. 1248-1259 Journal article (peer-reviewed)abstract Aim: Continuous pain occurs routinely, even after invasive procedures, or inflammation and surgery, but clinical practices associated with assessments of continuous pain remain unknown.Methods: A prospective cohort study in 243 Neonatal Intensive Care Units (NICUs) from 18 European countries recorded frequency of pain assessments, use of mechanical ventilation, sedation, analgesia, or neuromuscular blockade for each neonate upto 28 days after NICU admission.Results: Only 2113/6648 (31·8%) of neonates received assessments of continuous pain, occurring variably among tracheal ventilation (TrV, 46·0%), noninvasive ventilation (NiV, 35·0%), and no ventilation (NoV, 20·1%) groups (p<0·001). Daily assessments for continuous pain occurred in only 10·4% of all neonates (TrV: 14·0%, NiV: 10·7%, NoV: 7·6%; p<0·001). More frequent assessments of continuous pain occurred in NICUs with pain guidelines, nursing champions, and surgical admissions prompted (all p<0·01), and for newborns <32 weeks gestational age, those requiring ventilation, or opioids, sedatives-hypnotics, general anesthetics (O-SH-GA) (all p<0·001), or surgery (p=0·028). Use of O-SH-GA drugs increased the odds for pain assessment in the TrV (OR:1·60, p<0·001) and NiV groups (OR:1·40, p<0·001).Conclusion: Assessments of continuous pain occurred in less than one-third of NICU admissions, and daily in only 10% of neonates. NICU clinical practices should consider including routine assessments of continuous pain in newborns.
18.	Andersén, Annelie, 1977- (author) Ett särskilt perspektiv på högre studier? : Folkhögskoledeltagares sociala representationer om högskola och universitet 2011 Doctoral thesis (other academic/artistic)abstract Avhandlingen syftar till att undersöka folkhögskoledeltagares sociala representationer om högskola och universitet. Enligt teorin om sociala representationer är folkhögskoledeltagarnas sociala representationer om högskola och universitet något som skapas socialt och förändras beroende på deltagarnas erfarenheter av högskola och universitet. Avhandlingen syftar också till att undersöka dessa sociala representationers ursprung och framväxt, liksom om de har påverkats av andra sociala representationer exempelvis dem om folkhögskolans särart. För att identifiera folkhögskoledeltagarnas sociala identitet och sociala representationer har jag använt mig av empiriska data insamlat genom fria associationer och intervjuer med folkhögskoledeltagare och före detta folkhögskoledeltagare. För att undersöka representationernas ursprung har jag genomfört en dokumentstudie på folkhögskolelärarnas tidskrift. Resultaten visar att folkhögskolans företrädare genom hela folkhögskolans historia har förhållit sig till två huvudidéer, den om folkhögskolans särart och den om att folkhögskolan är en institution som anpassar sig efter det omkringliggande samhället och dess krav. Dessa båda idéer förklarar varför olika sociala identiteter och olika sociala representationer existerar bland folkhögskoledeltagarna. Grundidén att folkhögskolan har en särart leder till representationer om folkhögskolan som ett alternativ till annan utbildning och högskola och universitet som något som inte är likt folkhögskola. Den andra grundläggande idén om folkhögskolan som en institution som ständigt anpassar sig leder till representationer om folkhögskolan som en andra chans och högskolan som mål.
19.	Andersen, Christina, et al. (author) Berggrundsgeologi i området Asmundstjärn-Lysedtjärnet-Västra Silen, Värmland 2007 Reports (other academic/artistic)
20.	Andersen, Christina (author) Cookstoves, Candles, and Phthalates – Real Time Physicochemical Characterization and Human Exposure to Indoor Aerosols 2021 Doctoral thesis (other academic/artistic)abstract Exposure to air pollution is associated with adverse health effects in humans, with special concern for exposure to fine particulate matter (PM2.5). The physicochemical properties of aerosols impact the health effects. Considering that we spend approximately 90% of our time indoors, it is important to gain increased understanding of indoor aerosol concentrations and properties. The overall aim of the research presented in this thesis was to characterize the physicochemical properties of indoor aerosols from cookstoves, candles, and phthalate sources, and to assess their contribution to human exposure. Aerosol mass spectrometry (AMS) was applied for real time measurements of the aerosol chemical composition and concentration throughout the measurements included in the thesis.Emissions from four different cookstoves commonly used in sub Saharan Africa were measured with AMS and interpreted on the basis of a simplified framework describing the thermochemical conversion of biomass. The framework was validated by a correlation analysis of the included emission classes. Moreover, the results showed reduced PM1 emissions for more advanced stoves. However, pollutants which are of specific health concern, were not reduced in proportion to PM1. Even when PM1 emissions were reduced, high emissions of pollutants that have a strong impact on health and climate may be emitted, for example polycyclic aromatic compounds (PAHs) and refractory black carbon (rBC). The framework may be applied to estimate emissions of classes that were not measured in the experiments.Aerosol emissions from stressed burning of five types of candles of different wax and wick compositions were studied. We found strong variations between the candle types in emissions of PM2.5, BC, and PAHs, as well as strong variations over time, depending on the wax and wick composition. Candle emissions from stressed burning were dominated by BC emissions, with minor contributions from inorganic and organic aerosol emissions. The candles that emitted the lowest BC concentrations showed high emissions of ultrafine particles. NOx, formaldehyde, and gas-phase PAHs showed less variation between candle types and proved difficult to reduce by altering the wax and wick composition. The emissions of particle phase PAHs, BC, and organic aerosol showed strong correlations at the stressed burning of candles, and may be used as proxies for each other.The sorption of di-(2-ethyhexyl) phthalate (DEHP) on laboratory generated ammonium sulfate particles and indoor air particles was investigated by passing the particles through a 1.2 L chamber equipped with polyvinyl chloride (PVC) flooring. A higher sorption of DEHP to indoor particles, with a higher organic mass fraction, was measured compared to laboratory generated ammonium sulfate particles. In presence of airborne particles the emission of DEHP from PVC flooring increased. Thus, when particles are present in indoor air, the airborne concentration of DEHP available for respiratory deposition may increase. The sorption of DEHP on particles depends on the particle chemical composition. Organic particle concentrations are often high indoors, which promotes the sorption of DEHP and other SVOCs, which in turn may contribute to increased human exposure to DEHP and other SVOCs. This highlights the need to reduce health detrimental chemicals in consumer products and building materials, and to reduce particle concentrations in indoor environments.A human exposure study was conducted to elucidate the dermal and inhalation uptake in 16 volunteers from exposure to airborne gas- and particle phase phthalates, with participants wearing clean clothing. The uptake was measured, via combined inhalation and dermal air-to-skin transfer and via air-to-skin transfer only for the gas-phase diethyl phthalate (DEP) and for particle phase DEHP. Dermal uptake via air-to-skin transfer only with clean clothing acting as a barrier was ten times lower than the uptake via inhalation for DEP. Only uptake via inhalation was measurable for the particle phase DEHP. DEHP uptake via the skin was below the detection limit. The uptake of the gas-phase DEP via inhalation was four times higher compared to the particle phase DEHP, which reflects the differences in the lung deposition of gases and particles. The physicochemical properties of SVOCs influence their gas-particle partitioning and the likelihood of uptake via both inhalation and the skin, which should be considered in risk assessments of SVOCs.The results presented in this thesis highlight the importance of detailed physicochemical characterization of indoor aerosols, and the need for a more complete evaluation of their impact on human health.
21.	Andersen, Christina, et al. (author) Emissions of soot, PAHs, ultrafine particles, NOx, and other health relevant compounds from stressed burning of candles in indoor air 2021 In: Indoor Air. - : Hindawi Limited. - 0905-6947 .- 1600-0668. ; 31:6, s. 2033-2048 Journal article (peer-reviewed)abstract Burning candles release a variety of pollutants to indoor air, some of which are of concern for human health. We studied emissions of particles and gases from the stressed burning of five types of pillar candles with different wax and wick compositions. The stressed burning was introduced by controlled fluctuating air velocities in a 21.6 m3 laboratory chamber. The aerosol physicochemical properties were measured both in well-mixed chamber air and directly above the candle flame with online and offline techniques. All candles showed different emission profiles over time with high repeatability among replicates. The particle mass emissions from stressed burning for all candle types were dominated by soot (black carbon; BC). The wax and wick composition strongly influenced emissions of BC, PM2.5 , and particle-phase polycyclic aromatic hydrocarbons (PAHs), and to lower degree ultrafine particles, inorganic and organic carbon fraction of PM, but did not influence NOx , formaldehyde, and gas-phase PAHs. Measurements directly above the flame showed empirical evidence of short-lived strong emission peaks of soot particles. The results show the importance of including the entire burn time of candles in exposure assessments, as their emissions can vary strongly over time. Preventing stressed burning of candles can reduce exposure to pollutants in indoor air.
22.	Andersen, Christina, et al. (author) Inhalation and dermal uptake of particle and gas phase phthalates - A human chamber exposure study 2018 In: 15th Conference of the International Society of Indoor Air Quality and Climate, INDOOR AIR 2018. - 9781713826514 Conference paper (peer-reviewed)abstract We have exposed sixteen test subjects to particle and gas phase phthalates in the controlled chamber exposure study. Deuterium labelled phthalates were used to generate particle D4-DEHP (di(2-ethylhexyl) phthalate) and gas phase D4-DEP (diethyl phthalate) for exposures scenarios allowed studying the dermal only and combined inhalational and dermal uptake. Metabolites were measured in urine samples before and after three hours of exposure. The inhalation was the dominant route of uptake for both DEHP and DEP in this study design and exposure settings. Larger uptake of DEP compared to DEHP both via inhalation and dermal uptake was observed. Dermal uptake of DEHP was not observed in this study. Inhalational urinary excretion factors of the metabolites were found to be 0.73 for DEHP and 0.53 for DEP. This study also highlights the importance of taking into consideration the deposited dose of inhaled particles in studies of uptake of particles.
23.	Andersen, Christina, et al. (author) Inhalation and Dermal Uptake of Particle and Gas-phase Phthalates - A Human Exposure Study 2018 In: Environmental Science & Technology. - : American Chemical Society (ACS). - 1520-5851 .- 0013-936X. ; 52:21, s. 12792-12800 Journal article (peer-reviewed)abstract Phthalates are ubiquitous in indoor environments, which raises concern about their endocrine disrupting properties. However, studies of human uptake from airborne exposure are limited. We studied the inhalation uptake and dermal uptake by air-to-skin transfer with clean clothing as a barrier of two deuterium-labelled airborne phthalates: particle-phase D4-DEHP (di-(2-ethylhexyl)phthalate) and gas-phase D4-DEP (diethyl phthalate). Sixteen participants, wearing trousers and long-sleeved shirts, were under controlled conditions exposed to airborne phthalates in four exposure scenarios: dermal uptake alone, and combined inhalation+dermal uptake of both phthalates. The results showed an average uptake of D4-DEHP by inhalation of 0.0014±0.00088 (µg kg-1 bw)/(µg m-3)/h. No dermal uptake of D4-DEHP was observed during the 3 hour exposure with clean clothing. The deposited dose of D4-DEHP accounted for 26% of the total inhaled D4-DEHP mass. For D4-DEP, the average uptake by inhalation+dermal was 0.0067±0.0045 and 0.00073±0.00051 (µg kg-1 bw)/(µg m-3)/h for dermal uptake. Urinary excretion factors of metabolites after inhalation were estimated to 0.69 for D4-DEHP and 0.50 for D4-DEP. Under the described settings, the main uptake of both phthalates was through inhalation. The results demonstrate the differences in uptake of gas and particles, and highlights the importance of considering the deposited dose in particle uptake studies.
24.	Arlien-Soborg, Mai C., et al. (author) Acromegaly management in the Nordic countries: A Delphi consensus survey 2024 In: Clinical Endocrinology. - : WILEY. - 0300-0664 .- 1365-2265. Journal article (peer-reviewed)abstract ObjectiveAcromegaly is associated with increased morbidity and mortality if left untreated. The therapeutic options include surgery, medical treatment, and radiotherapy. Several guidelines and recommendations on treatment algorithms and follow-up exist. However, not all recommendations are strictly evidence-based. To evaluate consensus on the treatment and follow-up of patients with acromegaly in the Nordic countries.MethodsA Delphi process was used to map the landscape of acromegaly management in Denmark, Sweden, Norway, Finland, and Iceland. An expert panel developed 37 statements on the treatment and follow-up of patients with acromegaly. Dedicated endocrinologists (n = 47) from the Nordic countries were invited to rate their extent of agreement with the statements, using a Likert-type scale (1-7). Consensus was defined as >= 80% of panelists rating their agreement as >= 5 or <= 3 on the Likert-type scale.ResultsConsensus was reached in 41% (15/37) of the statements. Panelists agreed that pituitary surgery remains first line treatment. There was general agreement to recommend first-generation somatostatin analog (SSA) treatment after failed surgery and to consider repeat surgery. In addition, there was agreement to recommend combination therapy with first-generation SSA and pegvisomant as second- or third-line treatment. In more than 50% of the statements, consensus was not achieved. Considerable disagreement existed regarding pegvisomant monotherapy, and treatment with pasireotide and dopamine agonists.ConclusionThis consensus exploration study on the management of patients with acromegaly in the Nordic countries revealed a relatively large degree of disagreement among experts, which mirrors the complexity of the disease and the shortage of evidence-based data.
25.	Arlien-Søborg, Mai C., et al. (author) Acromegaly management in the nordic countries : a Delphi consensus survey 2024 In: Clinical Endocrinology. - : John Wiley & Sons. - 0300-0664 .- 1365-2265. Journal article (peer-reviewed)abstract Objective: Acromegaly is associated with increased morbidity and mortality if left untreated. The therapeutic options include surgery, medical treatment, and radiotherapy. Several guidelines and recommendations on treatment algorithms and follow-up exist. However, not all recommendations are strictly evidence-based. To evaluate consensus on the treatment and follow-up of patients with acromegaly in the Nordic countries.Methods: A Delphi process was used to map the landscape of acromegaly management in Denmark, Sweden, Norway, Finland, and Iceland. An expert panel developed 37 statements on the treatment and follow-up of patients with acromegaly. Dedicated endocrinologists (n = 47) from the Nordic countries were invited to rate their extent of agreement with the statements, using a Likert-type scale (1−7). Consensus was defined as ≥80% of panelists rating their agreement as ≥5 or ≤3 on the Likert-type scale.Results: Consensus was reached in 41% (15/37) of the statements. Panelists agreed that pituitary surgery remains first line treatment. There was general agreement to recommend first-generation somatostatin analog (SSA) treatment after failed surgery and to consider repeat surgery. In addition, there was agreement to recommend combination therapy with first-generation SSA and pegvisomant as second- or third-line treatment. In more than 50% of the statements, consensus was not achieved. Considerable disagreement existed regarding pegvisomant monotherapy, and treatment with pasireotide and dopamine agonists.Conclusion: This consensus exploration study on the management of patients with acromegaly in the Nordic countries revealed a relatively large degree of disagreement among experts, which mirrors the complexity of the disease and the shortage of evidence-based data.
26.	Assimes, Themistocles L., et al. (author) Lack of Association Between the Trp719Arg Polymorphism in Kinesin-Like Protein-6 and Coronary Artery Disease in 19 Case-Control Studies 2010 In: Journal of the American College of Cardiology. - : Elsevier BV. - 0735-1097. ; 56:19, s. 1552-1563 Journal article (peer-reviewed)abstract Objectives We sought to replicate the association between the kinesin-like protein 6 (KIF6) Trp719Arg polymorphism (rs20455), and clinical coronary artery disease (CAD). Background Recent prospective studies suggest that carriers of the 719Arg allele in KIF6 are at increased risk of clinical CAD compared with noncarriers. Methods The KIF6 Trp719Arg polymorphism (rs20455) was genotyped in 19 case-control studies of nonfatal CAD either as part of a genome-wide association study or in a formal attempt to replicate the initial positive reports. Results A total of 17,000 cases and 39,369 controls of European descent as well as a modest number of South Asians, African Americans, Hispanics, East Asians, and admixed cases and controls were successfully genotyped. None of the 19 studies demonstrated an increased risk of CAD in carriers of the 719Arg allele compared with noncarriers. Regression analyses and fixed-effects meta-analyses ruled out with high degree of confidence an increase of >= 2% in the risk of CAD among European 719Arg carriers. We also observed no increase in the risk of CAD among 719Arg carriers in the subset of Europeans with early-onset disease (younger than 50 years of age for men and younger than 60 years of age for women) compared with similarly aged controls as well as all non-European subgroups. Conclusions The KIF6 Trp719Arg polymorphism was not associated with the risk of clinical CAD in this large replication study. (J Am Coll Cardiol 2010;56:1552-63) (C) 2010 by the American College of Cardiology Foundation
27.	Bentham, James, et al. (author) A century of trends in adult human height 2016 In: eLIFE. - 2050-084X. ; 5 Journal article (peer-reviewed)abstract Being taller is associated with enhanced longevity, and higher education and earnings. We reanalysed 1472 population-based studies, with measurement of height on more than 18.6 million participants to estimate mean height for people born between 1896 and 1996 in 200 countries. The largest gain in adult height over the past century has occurred in South Korean women and Iranian men, who became 20.2 cm (95% credible interval 17.522.7) and 16.5 cm (13.319.7) taller, respectively. In contrast, there was little change in adult height in some sub-Saharan African countries and in South Asia over the century of analysis. The tallest people over these 100 years are men born in the Netherlands in the last quarter of 20th century, whose average heights surpassed 182.5 cm, and the shortest were women born in Guatemala in 1896 (140.3 cm; 135.8144.8). The height differential between the tallest and shortest populations was 19-20 cm a century ago, and has remained the same for women and increased for men a century later despite substantial changes in the ranking of countries.
28.	Bentham, James, et al. (author) A century of trends in adult human height 2016 In: eLIFE. - : eLife Sciences Publications Ltd. - 2050-084X. ; 5 Journal article (peer-reviewed)abstract Being taller is associated with enhanced longevity, and higher education and earnings. We reanalysed 1472 population-based studies, with measurement of height on more than 18.6 million participants to estimate mean height for people born between 1896 and 1996 in 200 countries. The largest gain in adult height over the past century has occurred in South Korean women and Iranian men, who became 20.2 cm (95% credible interval 17.5–22.7) and 16.5 cm (13.3– 19.7) taller, respectively. In contrast, there was little change in adult height in some sub-Saharan African countries and in South Asia over the century of analysis. The tallest people over these 100 years are men born in the Netherlands in the last quarter of 20th century, whose average heights surpassed 182.5 cm, and the shortest were women born in Guatemala in 1896 (140.3 cm; 135.8– 144.8). The height differential between the tallest and shortest populations was 19-20 cm a century ago, and has remained the same for women and increased for men a century later despite substantial changes in the ranking of countries.
29.	Berglund, Erik, et al. (author) Clinical Significance of Alloantibodies in Hand Transplantation : A Multicenter Study 2019 In: Transplantation. - : LIPPINCOTT WILLIAMS & WILKINS. - 0041-1337 .- 1534-6080. ; 103:10, s. 2173-2182 Journal article (peer-reviewed)abstract Background. Donor-specific antibodies (DSAs) have a strong negative correlation with long-term survival in solid organ transplantation. Although the clinical significance of DSA and antibody-mediated rejection (AMR) in upper extremity transplantation (UET) remains to be established, a growing number of single-center reports indicate their presence and potential clinical impact. Methods. We present a multicenter study assessing the occurrence and significance of alloantibodies in UET in reference to immunological parameters and functional outcome. Results. Our study revealed a high prevalence and early development of de novo DSA and non-DSA (43%, the majority detected within the first 3 postoperative y). HLA class II mismatch correlated with antibody development, which in turn significantly correlated with the incidence of acute cellular rejection. Cellular rejections preceded antibody development in almost all cases. A strong correlation between DSA and graft survival or function cannot be statistically established at this early stage but a correlation with a lesser outcome seems to emerge. Conclusions. While the phenotype and true clinical effect of AMR remain to be better defined, the high prevalence of DSA and the correlation with acute rejection highlight the need for optimizing immunosuppression, close monitoring, and the relevance of an HLA class II match in UET recipients.
30.	Blanner, Christina, et al. (author) Experiences of becoming widowed in old age–a cross-countries study with qualitative interviews from Denmark and quantitative measures of association in a Swedish sample 2021 In: International Journal of Qualitative Studies on Health and Well-being. - : Informa UK Limited. - 1748-2623 .- 1748-2631. ; 16:1 Journal article (peer-reviewed)abstract Purpose: Becoming widowed is a stressful health-threatening event causing major life changes. We explored how widowed people experience becoming widowed and examined if these experiences are quantitatively associated with widowhood. Methods: A multi-methods study using an exploratory sequential mixed-methods approach including a qualitative descriptive study with widowed people from Denmark and a Swedish cohort study. Qualitative interviews (n = 9) were analysed using qualitative content analysis, describing experiences as explained by the widowed people. The quantitative association of the experiences was examined by identifying proxies for the qualitative experiences of widowhood in the cohort study and examining the occurrence in widowed people compared to married people (n = 1,095). Results: Six categories of experiences emerged: the circumstances around spousal death, mental health and well-being, physical health, social relations, activities and practicalities. The quantitative examination showed a significant association with widowhood regarding mental and physical health problems. Conclusion: The circumstances around spousal death and the time before spousal death, in general, were important to how participants felt being widowed. Being ill negatively affected mental health and well-being, partly because of the inability to participate in activities and social relations. This is important, as health problems are more common among widowed people than married people.
31.	Blumen, Sergiu C, et al. (author) Aggressive familial ALS with unusual brain MRI and a SOD1 gene mutation. 2010 In: Amyotrophic Lateral Sclerosis and other Motor Neuron Disorders. - : Informa Healthcare. - 1466-0822 .- 1743-4483. ; 11:1-2, s. 228-231 Journal article (peer-reviewed)abstract We studied two sisters with rapidly progressing ALS starting at the ages of 46 and 48 years and leading to death after 14 months. Both fulfilled the El Escorial criteria for definite ALS and had marked upper motor neuron (UMN) predominance. Brain MRI, on fluid attenuation recovery (FLAIR) mode, showed outstanding hyperintensities of the precentral gyrus, centrum semiovale, corona radiata and along the corticospinal pathways in the brainstem. Screening for the SOD1 gene disclosed, at codon 140, a base substitution of adenine for thymine (GGT>CCA) known as the A140A 'silent' mutation since it does not change the amino acid (alanine) encoded for at that position. The severe UMN involvement and the fast progression of the disease may correlate with the MRI findings. It is also possible that the A140A mutation is not incidental; the mutated mRNA might be cytotoxic.
32.	Bomberg Andersen, Christina (author) Trace element analysis of orthopyroxene from the basal series in the Stillwater Complex 2008 Reports (other academic/artistic)
33.	Brekke, Morten, et al. (author) Flexible learning and teaching : Thematic Peer Group Report 2024 Reports (other academic/artistic)abstract European higher education institutions (HEIs) are facing increasing demands for more flexible learning and flexibility in learning paths.This report from a 2023 European University Association Learning & Teaching Thematic Peer Group on “Flexible learning and teaching” explores the complexity of implementing flexible learning at HEIs, starting by defining what it means and entails for the institution, and its members and entities (staff, students, leadership, faculties). With the view that the development of flexible learning is an essential condition for the future of learning at universities, the group identified challenges and examples of practice, and offered recommendations for institutions to reflect on their strategy and build capacity for flexible learning.
34.	Bruno, Raphael Romano, et al. (author) Management and outcomes in critically ill nonagenarian versus octogenarian patients 2021 In: BMC Geriatrics. - : BMC. - 1471-2318. ; 21:1 Journal article (peer-reviewed)abstract Background: Intensive care unit (ICU) patients age 90 years or older represent a growing subgroup and place a huge financial burden on health care resources despite the benefit being unclear. This leads to ethical problems. The present investigation assessed the differences in outcome between nonagenarian and octogenarian ICU patients. Methods: We included 7900 acutely admitted older critically ill patients from two large, multinational studies. The primary outcome was 30-day-mortality, and the secondary outcome was ICU-mortality. Baseline characteristics consisted of frailty assessed by the Clinical Frailty Scale (CFS), ICU-management, and outcomes were compared between octogenarian (80-89.9 years) and nonagenarian (>= 90 years) patients. We used multilevel logistic regression to evaluate differences between octogenarians and nonagenarians. Results: The nonagenarians were 10% of the entire cohort. They experienced a higher percentage of frailty (58% vs 42%; p < 0.001), but lower SOFA scores at admission (6 +/- 5 vs. 7 +/- 6; p < 0.001). ICU-management strategies were different. Octogenarians required higher rates of organ support and nonagenarians received higher rates of life-sustaining treatment limitations (40% vs. 33%; p < 0.001). ICU mortality was comparable (27% vs. 27%; p = 0.973) but a higher 30-day-mortality (45% vs. 40%; p = 0.029) was seen in the nonagenarians. After multivariable adjustment nonagenarians had no significantly increased risk for 30-day-mortality (aOR 1.25 (95% CI 0.90-1.74; p = 0.19)). Conclusion: After adjustment for confounders, nonagenarians demonstrated no higher 30-day mortality than octogenarian patients. In this study, being age 90 years or more is no particular risk factor for an adverse outcome. This should be considered- together with illness severity and pre-existing functional capacity - to effectively guide triage decisions.
35.	Carter, David, et al. (author) Translation Methodology in the Spoken Language Translator: An Evaluation 1997 In: Proceedings of ACL/EACL workshop Spoken Language Translation. ; , s. 73-81 Conference paper (peer-reviewed)abstract In this paper we describe how the translation methodology adopted fro the Spoken Language Translator (SLT) addresses the characteristics of the speech translation task in a context where it is essential to achieve easy customization to new languages and new domains. We then discuss the issues that arise in any attempt to evaluate a speech translator, and present results of such an evaluation carried out on SLT for several language pairs.
36.	Clausen, Bettina Hjelm, et al. (author) Conditional ablation of myeloid TNF increases lesion volume after experimental stroke in mice, possibly via altered ERK1/2 signaling 2016 In: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 6 Journal article (peer-reviewed)abstract Microglia are activated following cerebral ischemia and increase their production of the neuro- and immunomodulatory cytokine tumor necrosis factor (TNF). To address the function of TNF from this cellular source in focal cerebral ischemia we used TNF conditional knock out mice (LysMcreTNF fl/fl) in which the TNF gene was deleted in cells of the myeloid lineage, including microglia. The deletion reduced secreted TNF levels in lipopolysaccharide-stimulated cultured primary microglia by ∼93%. Furthermore, phosphorylated-ERK/ERK ratios were significantly decreased in naïve LysMcreTNF fl/fl mice demonstrating altered ERK signal transduction. Micro-PET using 18 [F]-fluorodeoxyglucose immediately after focal cerebral ischemia showed increased glucose uptake in LysMcreTNF fl/fl mice, representing significant metabolic changes, that translated into increased infarct volumes at 24 hours and 5 days compared to littermates (TNFfl/fl). In naïve LysMcreTNF fl/fl mice cytokine levels were low and comparable to littermates. At 6 hours, TNF producing microglia were reduced by 56% in the ischemic cortex in LysMcreTNF fl/fl mice compared to littermate mice, whereas no TNF + leukocytes were detected. At 24 hours, pro-inflammatory cytokine (TNF, IL-1β, IL-6, IL-5 and CXCL1) levels were significantly lower in LysMcreTNF fl/fl mice, despite comparable infiltrating leukocyte populations. Our results identify microglial TNF as beneficial and neuroprotective in the acute phase and as a modulator of neuroinflammation at later time points after experimental ischemia, which may contribute to regenerative recovery.
37.	de Vries, Claire E. E., et al. (author) Outcomes of the first global multidisciplinary consensus meeting including persons living with obesity to standardize patient-reported outcome measurement in obesity treatment research 2022 In: Obesity Reviews. - : John Wiley & Sons. - 1467-7881 .- 1467-789X. ; 23:8 Journal article (peer-reviewed)abstract Quality of life is a key outcome that is not rigorously measured in obesity treatment research due to the lack of standardization of patient-reported outcomes (PROs) and PRO measures (PROMs). The S.Q.O.T. initiative was founded to Standardize Quality of life measurement in Obesity Treatment. A first face-to-face, international, multidisciplinary consensus meeting was conducted to identify the key PROs and preferred PROMs for obesity treatment research. It comprised of 35 people living with obesity (PLWO) and healthcare providers (HCPs). Formal presentations, nominal group techniques, and modified Delphi exercises were used to develop consensus-based recommendations. The following eight PROs were considered important: self-esteem, physical health/functioning, mental/psychological health, social health, eating, stigma, body image, and excess skin. Self-esteem was considered the most important PRO, particularly for PLWO, while physical health was perceived to be the most important among HCPs. For each PRO, one or more PROMs were selected, except for stigma. This consensus meeting was a first step toward standardizing PROs (what to measure) and PROMs (how to measure) in obesity treatment research. It provides an overview of the key PROs and a first selection of the PROMs that can be used to evaluate these PROs.
38.	Eklund, Robert, 1962-, et al. (author) Rational Re-Use of Linguistic Data 2000 In: The Spoken Language Translator. - Cambridge : Cambridge University Press. - 0521770777 - 9780521770774 ; , s. 212-228 Book chapter (other academic/artistic)abstract This book presents a detailed description of Spoken Language Translator (SLT), one of the first major projects in the area of automatic speech translation. The SLT system can translate between English, French, and Swedish in the domain of air travel planning, using a vocabulary of about 1500 words, and with an accuracy of about 75%. The greater part of the book describes the language processing components, which are largely built on top of the SRI Core Language Engine, using a combination of general grammars and techniques that allow them to be rapidly customized to specific domains. Speech recognition is based on Hidden Markov Mode technology, and uses versions of the SRI DECIPHER system. This account of the Spoken Language Translator should be an essential resource both for those who wish to know what is achievable in spoken-language translation today, and for those who wish to understand how to achieve it.
39.	El-Houri, Rime B., et al. (author) Methylisothiazolinone in a designer spectacle frame – a surprising finding 2016 In: Contact Dermatitis. - : Wiley. - 0105-1873. ; 75:5, s. 310-312 Journal article (peer-reviewed)
40.	Eriksson, Axel Christian, et al. (author) Influence of airborne particles' chemical composition on SVOC uptake from PVC flooring - time resolved analysis with aerosol mass spectrometry 2020 In: Environmental Science & Technology. - : American Chemical Society (ACS). - 1520-5851 .- 0013-936X. ; , s. 85-91 Journal article (peer-reviewed)abstract We sampled ammonium sulfate particles and indoor particles of outdoor origin through a small chamber covered with polyvinyl chloride (PVC) flooring. We measured the uptake of semi-volatile organic compounds (SVOC) by the airborne particles in real time. The particles acquired SVOC mass fractions up to 10%. The phthalate ester DEHP (di(2-ethylhexyl)phthalate), a known endocrine disruptor, contributed by approximately half of the sorbed SVOC mass. The indoor particles acquired higher DEHP fraction than laboratory generated ammonium sulfate aerosol. We attribute this increased uptake to absorption by organic matter present in the indoor particles. Using a thermodenuder to remove volatile components, predominantly organics, reduced SVOC uptake. Positive matrix factorization applied to the organic mass spectra suggests that hydrocarbon-like organic aerosol (typically fresh traffic exhaust) sorbs DEHP more efficiently than aged organic aerosol. SVOC uptake is one of the processes that modifies outdoor pollution particles after they penetrate buildings, where the majority of exposure occurs. Particles from indoor sources, typically dominated by organic matter, will undergo such processes as well. Aerosol mass spectrometry improves the time resolution of experimental investigations into these processes, and enables experiments with lower, relevant particle concentrations. Additionally, particle size resolved results are readily obtained.
41.	Eriksson, Axel C., et al. (author) Phthalate uptake by aerosol particles and humans - time resolved analysis with aerosol mass spectrometry 2020 In: 16th Conference of the International Society of Indoor Air Quality and Climate : Creative and Smart Solutions for Better Built Environments, Indoor Air 2020 - Creative and Smart Solutions for Better Built Environments, Indoor Air 2020. - 9781713823605 ; , s. 782-784 Conference paper (peer-reviewed)
42.	Eriksson, Axel C., et al. (author) The role of organic fraction of aerosol particles in uptake of indoor SVOC investigated with real time aerosol mass spectrometry 2018 In: 15th Conference of the International Society of Indoor Air Quality and Climate, INDOOR AIR 2018. - 9781713826514 Conference paper (peer-reviewed)abstract We investigate the uptake of the Di(2-ethylhexyl) phthalate (DEHP) by laboratory generated and ambient aerosol particles passing through a 1.2 liter chamber covered with vinyl flooring on its internal surfaces. We found approximately five times more efficient DEHP uptake on a mass basis by organic particles (ambient particles) compared to laboratory generated salt particles. The increased uptake is likely due to increased adsorption by pre-existing organic aerosol, which is abundant in the ambient aerosol particles. This implies that compounds with adverse health outcomes are added to particles in indoor air after infiltration into buildings via gas-to-particle conversion of indoor generated SVOCs. We show that aerosol mass spectrometry is a suitable tool for highly time-resolved investigations of this process.
43.	Eriksson, Axel, et al. (author) Health Detrimental SVOC Uptake by Infiltrating Ambient Particles Measured with Soot Particle Aerosol Mass Spectrometry 2018 In: International Aerosol Conference. Conference paper (other academic/artistic)
44.	Eskelund, Christian W., et al. (author) TP53 mutations identify younger mantle cell lymphoma patients who do not benefit from intensive chemoimmunotherapy 2017 In: Blood. - : American Society of Hematology. - 0006-4971 .- 1528-0020. ; 130:17, s. 1903-1910 Journal article (peer-reviewed)abstract Despite recent advances in lymphoma treatment, mantle cell lymphoma (MCL) remains incurable, and we are still unable to identify patients who will not benefit from the current standard of care. Here, we explore the prognostic value of recurrent genetic aberrations in diagnostic bone marrow (BM) specimens from 183 younger patients with MCL from the Nordic MCL2 and MCL3 trials, which represent current standard-of-care regimens. In the univariate model, mutations of TP53 (11%) and NOTCH1 (4%), and deletions of TP53 (16%) andCDKN2A(20%),weresignificantly associatedwithinferioroutcomes(togetherwithMIPI, MIPI-c, blastoidmorphology, and Ki67 > 30%); however, inmultivariate analyses, only TP53 mutations (HR, 6.2; P <.0001) retained prognostic impact for overall survival (OS), whereas TP53 mutations (HR, 6.9; P <.0001) andMIPI-c high-risk (HR, 2.6; P5.003) had independent prognostic impact on time to relapse. TP53-mutated cases had a dismal outcome, with a median OS of 1.8 years, and 50% relapsed at 1.0 years, compared to a median OS of 12.7 years for TP53-unmutated cases (P <.0001). TP53 mutations were significantly associated with Ki67 > 30%, blastoid morphology, MIPI high-risk, and inferior responses to both induction- and high-dose chemotherapy. In conclusion, we show that TP53mutations identify a phenotypically distinct and highly aggressive form of MCL with poor or no response to regimens including cytarabine, rituximab, and autologous stem-cell transplant (ASCT). We suggest patients with MCL should be stratified according to TP53 status, and that patients with TP53 mutations should be considered for experimental frontline trials exploring novel agents.
45.	Fosby, Bjarte, et al. (author) Liver transplantation in the Nordic countries - An intention to treat and post-transplant analysis from The Nordic Liver Transplant Registry 1982-2013. 2015 In: Scandinavian journal of gastroenterology. - : Informa UK Limited. - 1502-7708 .- 0036-5521. ; 50:6, s. 797-808 Journal article (peer-reviewed)abstract The Nordic Liver Transplant Registry (NLTR) accounts for all liver transplants performed in the Nordic countries since the start of the transplant program in 1982. Due to short waiting times, donor liver allocation has been made without considerations of the model of end-stage liver disease (MELD) score. We aimed to summarize key outcome measures and developments for the activity up to December 2013.
46.	Fronczek, Jakub, et al. (author) Relationship between the Clinical Frailty Scale and short-term mortality in patients ≥ 80 years old acutely admitted to the ICU : a prospective cohort study 2021 In: Critical Care. - : BioMed Central (BMC). - 1364-8535 .- 1466-609X. ; 25:1 Journal article (peer-reviewed)abstract BACKGROUND: The Clinical Frailty Scale (CFS) is frequently used to measure frailty in critically ill adults. There is wide variation in the approach to analysing the relationship between the CFS score and mortality after admission to the ICU. This study aimed to evaluate the influence of modelling approach on the association between the CFS score and short-term mortality and quantify the prognostic value of frailty in this context.METHODS: We analysed data from two multicentre prospective cohort studies which enrolled intensive care unit patients ≥ 80 years old in 26 countries. The primary outcome was mortality within 30-days from admission to the ICU. Logistic regression models for both ICU and 30-day mortality included the CFS score as either a categorical, continuous or dichotomous variable and were adjusted for patient's age, sex, reason for admission to the ICU, and admission Sequential Organ Failure Assessment score.RESULTS: The median age in the sample of 7487 consecutive patients was 84 years (IQR 81-87). The highest fraction of new prognostic information from frailty in the context of 30-day mortality was observed when the CFS score was treated as either a categorical variable using all original levels of frailty or a nonlinear continuous variable and was equal to 9% using these modelling approaches (p < 0.001). The relationship between the CFS score and mortality was nonlinear (p < 0.01).CONCLUSION: Knowledge about a patient's frailty status adds a substantial amount of new prognostic information at the moment of admission to the ICU. Arbitrary simplification of the CFS score into fewer groups than originally intended leads to a loss of information and should be avoided. Trial registration NCT03134807 (VIP1), NCT03370692 (VIP2).
47.	Fronczek, Jakub, et al. (author) Short-term mortality or patients >= 80 years old admitted to European intensive care units: an international observational study 2022 In: British Journal of Anaesthesia. - : ELSEVIER SCI LTD. - 0007-0912 .- 1471-6771. ; 129:1, s. 58-66 Journal article (peer-reviewed)abstract Background: Limited evidence suggests variation in mortality of older critically ill adults across Europe. We aimed to investigate regional differences in mortality among very old ICU patients. Methods: Multilevel analysis of two international prospective cohort studies. We included patients >= 80 yr old from 322 ICUs located in 16 European countries. The primary outcome was mortality within 30 days from admission to the ICU. Results are presented as n (%) with 95% confidence intervals and odds ratios (ORs). Results: Of 8457 patients, 2944 (36.9% [35.9-38.0%]) died within 30 days. Crude mortality rates varied widely between participating countries (from 10.1% [6.4-15.6%] to 45.1% [41.1-49.2%] in the ICU and from 21.3% [16.3-28.9%] to 55.3% [51.1-59.5%] within 30 days). After adjustment for confounding variables, the variation in 30-day mortality between countries was substantially smaller than between ICUs (median OR 1.14 vs 1.58). Healthcare expenditure per capita (OR=0.84 per $1000 [0.75-0.94]) and social health insurance framework (OR=1.43 [1.01-2.01]) were associated with ICU mortality, but the direction and magnitude of these relationships was uncertain in 30-day follow-up. Volume of admissions was associated with lower mortality both in the ICU (OR=0.81 per 1000 annual ICU admissions [0.71-0.94]) and in 30-day follow-up (OR=0.86 [0.76-0.97]). Conclusion: The apparent variation in short-term mortality rates of older adults hospitalised in ICUs across Europe can be largely attributed to differences in the clinical profile of patients admitted. The volume-outcome relationship identified in this population requires further investigation.
48.	Frøkjær, Jens Brøndum, et al. (author) Altered Brain Microstructure Assessed by Diffusion Tensor Imaging in Patients With Diabetes Mellitus and Gastrointestinal Symptoms. 2013 In: Diabetes care. - : American Diabetes Association. - 1935-5548 .- 0149-5992. ; 36:3, s. 662-668 Journal article (peer-reviewed)abstract OBJECTIVE In patients with long-standing diabetes mellitus (DM), there is increasing evidence for abnormal processing of gastrointestinal sensations in the central nervous system. Using magnetic resonance diffusion tensor imaging, we characterized brain microstructure in areas involved in visceral sensory processing and correlated these findings to clinical parameters.RESEARCH DESIGN AND METHODS Twenty-six patients with DM and gastrointestinal symptoms and 23 healthy control subjects were studied in a 3T scanner. The apparent diffusion coefficient (i.e., diffusivity of water) and fractional anisotropy (FA) (i.e., organization of fibers) were assessed in the "sensory matrix" (cingulate cortex, insula, prefrontal and secondary sensory cortex, amygdala, and corona radiata) and in corpus callosum.RESULTS Patients had decreased FA values compared with control subjects: 1) all areas (P = 0.025); 2) anterior (P < 0.001), mid- (P = 0.001), and posterior (P < 0.001) cingulate cortex; 3) prefrontal cortex gray matter (P < 0.001); 4) corona radiata (P < 0.001); 5) secondary sensory cortex (P = 0.008); 6) anterior white matter (P = 0.045); and anterior gray matter (P = 0.002) and posterior gray matter (P = 0.002) insula. No difference was found in corpus callosum (P > 0.05). The microstructural changes were for some areas correlated to clinical parameters such as bloating (anterior insula), mental well-being (anterior insula, prefrontal cortex, and mid-cingulated and corona radiata), autonomic function based on electrocardiographic results (posterior insula and anterior cingulate), and presence of gastroparesis (anterior insula).CONCLUSIONS The findings of this explorative study indicate that microstructural changes of brain areas involved in visceral sensory processing are associated with autonomic dysfunction and therefore may be involved in the pathogenesis of gastrointestinal symptoms in DM patients.
49.	Granberg, Tobias, et al. (author) Hereditary diffuse leukoencephalopathy with spheroids - a volumetric and radiological comparison with multiple sclerosis patients and healthy controls. 2016 In: European Journal of Neurology. - : Wiley. - 1351-5101 .- 1468-1331. ; 23:4, s. 817-822 Journal article (peer-reviewed)abstract Background and purpose Hereditary diffuse leukoencephalopathy with spheroids (HDLS) is an autosomal dominant disorder caused by colony-stimulating factor 1 receptor (CSF1R) gene mutations, resulting in demyelination and axonal degeneration with spheroids. The clinical expression is variable, including behavioral changes, cognitive impairment, motor symptoms and parkinsonism. Magnetic resonance imaging (MRI) reveals white matter (WM) changes and atrophy. The indistinct phenotype has led to misdiagnoses. This study's aim was to compare brain volumetry and radiological ratings in HDLS with multiple sclerosis (MS) patients and controls. Methods Five HDLS patients with c.2562T>A p.Asn854Lys CSF1R mutation, five age- and gender-matched MS patients and five healthy controls were cross-sectionally studied. All patients were examined neurologically. HDLS patients underwent Mini-Mental State Examination (MMSE). Brain MRI scans were analyzed volumetrically with FreeSurfer and Lesion Segmentation Toolbox and neuroradiologically with the brain MRI scoring system for HDLS. Results Patients with HDLS had lower brain, grey matter and WM fractions (66.3%; 37.9%; 27.6%) compared with controls (78.5%, P = 0.008; 44.4%, P = 0.008; 32.0%, P = 0.008), but not compared with MS patients (65.7%, P = 0.7; 36.8%, P = 0.4; 27.3%, P = 0.7). Cerebellar WM changes and atrophy were not seen in the HDLS group. The HDLS lesion volume fraction correlated with MMSE scores (r = −0.90, P = 0.04). Conclusions Brain volume fractions in HDLS were lower than in controls and similar to those seen in MS. The cerebellum was relatively spared in HDLS, which may help in differentiating HDLS WM changes from MS. The strong relationship of HDLS lesions with MMSE scores indicates that accumulating WM pathology in HDLS is associated with cognitive decline.
50.	Guidet, Bertrand, et al. (author) Withholding or withdrawing of life-sustaining therapy in older adults (≥ 80 years) admitted to the intensive care unit 2018 In: Intensive Care Medicine. - : Springer Science and Business Media LLC. - 0342-4642 .- 1432-1238. ; 44:7, s. 1027-1038 Journal article (peer-reviewed)abstract PURPOSE: To document and analyse the decision to withhold or withdraw life-sustaining treatment (LST) in a population of very old patients admitted to the ICU.METHODS: This prospective study included intensive care patients aged ≥ 80 years in 309 ICUs from 21 European countries with 30-day mortality follow-up.RESULTS: LST limitation was identified in 1356/5021 (27.2%) of patients: 15% had a withholding decision and 12.2% a withdrawal decision (including those with a previous withholding decision). Patients with LST limitation were older, more frail, more severely ill and less frequently electively admitted. Patients with withdrawal of LST were more frequently male and had a longer ICU length of stay. The ICU and 30-day mortality were, respectively, 29.1 and 53.1% in the withholding group and 82.2% and 93.1% in the withdrawal group. LST was less frequently limited in eastern and southern European countries than in northern Europe. The patient-independent factors associated with LST limitation were: acute ICU admission (OR 5.77, 95% CI 4.32-7.7), Clinical Frailty Scale (CFS) score (OR 2.08, 95% CI 1.78-2.42), increased age (each 5 years of increase in age had a OR of 1.22 (95% CI 1.12-1.34) and SOFA score [OR of 1.07 (95% CI 1.05-1.09 per point)]. The frequency of LST limitation was higher in countries with high GDP and was lower in religious countries.CONCLUSIONS: The most important patient variables associated with the instigation of LST limitation were acute admission, frailty, age, admission SOFA score and country.TRIAL REGISTRATION: ClinicalTrials.gov (ID: NTC03134807).

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