| 1. |
- Blokland, G. A. M., et al.
(författare)
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Sex-Dependent Shared and Nonshared Genetic Architecture Across Mood and Psychotic Disorders
- 2022
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Ingår i: Biological Psychiatry. - : Elsevier BV. - 0006-3223 .- 1873-2402. ; 91:1, s. 102-117
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Tidskriftsartikel (refereegranskat)abstract
- Background: Sex differences in incidence and/or presentation of schizophrenia (SCZ), major depressive disorder (MDD), and bipolar disorder (BIP) are pervasive. Previous evidence for shared genetic risk and sex differences in brain abnormalities across disorders suggest possible shared sex-dependent genetic risk. Methods: We conducted the largest to date genome-wide genotype-by-sex (G×S) interaction of risk for these disorders using 85,735 cases (33,403 SCZ, 19,924 BIP, and 32,408 MDD) and 109,946 controls from the PGC (Psychiatric Genomics Consortium) and iPSYCH. Results: Across disorders, genome-wide significant single nucleotide polymorphism–by-sex interaction was detected for a locus encompassing NKAIN2 (rs117780815, p = 3.2 × 10−8), which interacts with sodium/potassium-transporting ATPase (adenosine triphosphatase) enzymes, implicating neuronal excitability. Three additional loci showed evidence (p < 1 × 10−6) for cross-disorder G×S interaction (rs7302529, p = 1.6 × 10−7; rs73033497, p = 8.8 × 10−7; rs7914279, p = 6.4 × 10−7), implicating various functions. Gene-based analyses identified G×S interaction across disorders (p = 8.97 × 10−7) with transcriptional inhibitor SLTM. Most significant in SCZ was a MOCOS gene locus (rs11665282, p = 1.5 × 10−7), implicating vascular endothelial cells. Secondary analysis of the PGC-SCZ dataset detected an interaction (rs13265509, p = 1.1 × 10−7) in a locus containing IDO2, a kynurenine pathway enzyme with immunoregulatory functions implicated in SCZ, BIP, and MDD. Pathway enrichment analysis detected significant G×S interaction of genes regulating vascular endothelial growth factor receptor signaling in MDD (false discovery rate-corrected p < .05). Conclusions: In the largest genome-wide G×S analysis of mood and psychotic disorders to date, there was substantial genetic overlap between the sexes. However, significant sex-dependent effects were enriched for genes related to neuronal development and immune and vascular functions across and within SCZ, BIP, and MDD at the variant, gene, and pathway levels. © 2021 Society of Biological Psychiatry
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| 2. |
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| 3. |
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| 4. |
- de Jong, S, et al.
(författare)
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Applying polygenic risk scoring for psychiatric disorders to a large family with bipolar disorder and major depressive disorder
- 2018
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Ingår i: Communications biology. - : Springer Science and Business Media LLC. - 2399-3642. ; 1, s. 163-
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Tidskriftsartikel (refereegranskat)abstract
- Psychiatric disorders are thought to have a complex genetic pathology consisting of interplay of common and rare variation. Traditionally, pedigrees are used to shed light on the latter only, while here we discuss the application of polygenic risk scores to also highlight patterns of common genetic risk. We analyze polygenic risk scores for psychiatric disorders in a large pedigree (n ~ 260) in which 30% of family members suffer from major depressive disorder or bipolar disorder. Studying patterns of assortative mating and anticipation, it appears increased polygenic risk is contributed by affected individuals who married into the family, resulting in an increasing genetic risk over generations. This may explain the observation of anticipation in mood disorders, whereby onset is earlier and the severity increases over the generations of a family. Joint analyses of rare and common variation may be a powerful way to understand the familial genetics of psychiatric disorders.
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| 5. |
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| 6. |
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| 7. |
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| 8. |
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| 9. |
- Czamara, D, et al.
(författare)
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Integrated analysis of environmental and genetic influences on cord blood DNA methylation in new-borns
- 2019
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Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 10:1, s. 2548-
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Tidskriftsartikel (refereegranskat)abstract
- Epigenetic processes, including DNA methylation (DNAm), are among the mechanisms allowing integration of genetic and environmental factors to shape cellular function. While many studies have investigated either environmental or genetic contributions to DNAm, few have assessed their integrated effects. Here we examine the relative contributions of prenatal environmental factors and genotype on DNA methylation in neonatal blood at variably methylated regions (VMRs) in 4 independent cohorts (overall n = 2365). We use Akaike’s information criterion to test which factors best explain variability of methylation in the cohort-specific VMRs: several prenatal environmental factors (E), genotypes in cis (G), or their additive (G + E) or interaction (GxE) effects. Genetic and environmental factors in combination best explain DNAm at the majority of VMRs. The CpGs best explained by either G, G + E or GxE are functionally distinct. The enrichment of genetic variants from GxE models in GWAS for complex disorders supports their importance for disease risk.
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| 10. |
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| 11. |
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| 12. |
- Arnau-Soler, A, et al.
(författare)
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Genome-wide by environment interaction studies of depressive symptoms and psychosocial stress in UK Biobank and Generation Scotland
- 2019
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Ingår i: Translational psychiatry. - : Springer Science and Business Media LLC. - 2158-3188. ; 9:1, s. 14-
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Tidskriftsartikel (refereegranskat)abstract
- Stress is associated with poorer physical and mental health. To improve our understanding of this link, we performed genome-wide association studies (GWAS) of depressive symptoms and genome-wide by environment interaction studies (GWEIS) of depressive symptoms and stressful life events (SLE) in two UK population-based cohorts (Generation Scotland and UK Biobank). No SNP was individually significant in either GWAS, but gene-based tests identified six genes associated with depressive symptoms in UK Biobank (DCC, ACSS3, DRD2, STAG1, FOXP2 and KYNU; p < 2.77 × 10−6). Two SNPs with genome-wide significant GxE effects were identified by GWEIS in Generation Scotland: rs12789145 (53-kb downstream PIWIL4; p = 4.95 × 10−9; total SLE) and rs17070072 (intronic to ZCCHC2; p = 1.46 × 10−8; dependent SLE). A third locus upstream CYLC2 (rs12000047 and rs12005200, p < 2.00 × 10−8; dependent SLE) when the joint effect of the SNP main and GxE effects was considered. GWEIS gene-based tests identified: MTNR1B with GxE effect with dependent SLE in Generation Scotland; and PHF2 with the joint effect in UK Biobank (p < 2.77 × 10−6). Polygenic risk scores (PRSs) analyses incorporating GxE effects improved the prediction of depressive symptom scores, when using weights derived from either the UK Biobank GWAS of depressive symptoms (p = 0.01) or the PGC GWAS of major depressive disorder (p = 5.91 × 10−3). Using an independent sample, PRS derived using GWEIS GxE effects provided evidence of shared aetiologies between depressive symptoms and schizotypal personality, heart disease and COPD. Further such studies are required and may result in improved treatments for depression and other stress-related conditions.
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| 13. |
- Bryant, J. M., et al.
(författare)
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Emergence and spread of a human-transmissible multidrug-resistant nontuberculous mycobacterium
- 2016
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Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 354:6313, s. 751-757
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Tidskriftsartikel (refereegranskat)abstract
- Lung infections with Mycobacterium abscessus, a species of multidrug-resistant nontuberculous mycobacteria, are emerging as an important global threat to individuals with cystic fibrosis (CF), in whom M. abscessus accelerates inflammatory lung damage, leading to increased morbidity and mortality. Previously, M. abscessus was thought to be independently acquired by susceptible individuals from the environment. However, using whole-genome analysis of a global collection of clinical isolates, we show that the majority of M. abscessus infections are acquired through transmission, potentially via fomites and aerosols, of recently emerged dominant circulating clones that have spread globally. We demonstrate that these clones are associated with worse clinical outcomes, show increased virulence in cell-based and mouse infection models, and thus represent an urgent international infection challenge.
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| 14. |
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| 15. |
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| 16. |
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| 17. |
- Chatzikonstantinou, T, et al.
(författare)
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COVID-19 severity and mortality in patients with CLL: an update of the international ERIC and Campus CLL study
- 2021
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Ingår i: Leukemia. - : Springer Science and Business Media LLC. - 1476-5551 .- 0887-6924. ; 35:12, s. 3444-3454
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Tidskriftsartikel (refereegranskat)abstract
- Patients with chronic lymphocytic leukemia (CLL) may be more susceptible to Coronavirus disease 2019 (COVID-19) due to age, disease, and treatment-related immunosuppression. We aimed to assess risk factors of outcome and elucidate the impact of CLL-directed treatments on the course of COVID-19. We conducted a retrospective, international study, collectively including 941 patients with CLL and confirmed COVID-19. Data from the beginning of the pandemic until March 16, 2021, were collected from 91 centers. The risk factors of case fatality rate (CFR), disease severity, and overall survival (OS) were investigated. OS analysis was restricted to patients with severe COVID-19 (definition: hospitalization with need of oxygen or admission into an intensive care unit). CFR in patients with severe COVID-19 was 38.4%. OS was inferior for patients in all treatment categories compared to untreated (p < 0.001). Untreated patients had a lower risk of death (HR = 0.54, 95% CI:0.41–0.72). The risk of death was higher for older patients and those suffering from cardiac failure (HR = 1.03, 95% CI:1.02–1.04; HR = 1.79, 95% CI:1.04–3.07, respectively). Age, CLL-directed treatment, and cardiac failure were significant risk factors of OS. Untreated patients had a better chance of survival than those on treatment or recently treated.
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| 18. |
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| 19. |
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| 20. |
- Johansson, SE, et al.
(författare)
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Smokeless tobacco and coronary heart disease: a 12-year follow-up study
- 2005
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Ingår i: European journal of cardiovascular prevention and rehabilitation : official journal of the European Society of Cardiology, Working Groups on Epidemiology & Prevention and Cardiac Rehabilitation and Exercise Physiology. - : Oxford University Press (OUP). - 1741-8267. ; 12:4, s. 387-392
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Tidskriftsartikel (refereegranskat)abstract
- Background Cigarette smoking has declined whereas the use of smokeless tobacco is increasing. There is an ongoing debate as to whether smokeless tobacco is a recommendable strategy to help smokers to quit. However, very few studies have examined the association between smokeless tobacco, namely snuff, and coronary heart disease, which implies that it has not been possible to provide scientific results for public health policies and clinical guidelines concerning the use of smokeless tobacco. Design A follow-up study. Methods A random sample of 3120 healthy men aged 30–74 years was interviewed in 1988 and 1989 and followed up to the year 2000 with regard to coronary heart disease. Cox regression was used to estimate the relative risk of coronary heart disease in six categories of smoking and snuffing habits, after adjustment for established risk factors for coronary heart disease. Results Smokers, former smokers, and those who combined smoking and snuffing had significantly higher hazard ratios than never-smokers. The very highest hazard ratio was found among individuals combining smoking and snuffing. Daily snuffers had a hazard ratio of 1.62 (95% confidence interval 0.70–3.03) after adjustment for age. Conclusions Even though the association between daily snuffing and coronary heart disease was non-significant, the hazard ratio was markedly increased. Therefore, smokers should not use smokeless tobacco in order to quit smoking, especially as safer alternatives are available. Further studies in different settings are required to provide scientific results for public health policies and clinical guidelines.
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| 21. |
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| 22. |
- Sundquist, K, et al.
(författare)
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Does occupational social class predict coronary heart disease after retirement? A 12-year follow-up study in Sweden
- 2005
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Ingår i: Scandinavian journal of public health. - : SAGE Publications. - 1403-4948 .- 1651-1905. ; 33:6, s. 447-454
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Tidskriftsartikel (refereegranskat)abstract
- Aims: To examine whether socioeconomic status and coronary heart disease (CHD) risk factors remain significant predictors of CHD among people aged ≥65 years. Previous studies in this age group are few and inconsistent. Methods: Follow-up study of a simple random sample of Swedish women and men aged ≥65 years interviewed in a national survey 1988—89 and followed up until 31 December 2000, for CHD incidence rates. Cox regression was used to study the association between socioeconomic status (occupation) and CHD, after adjustment for age, sex, physical activity, smoking, BMI, diabetes, and hypertension. Participants with CHD hospitalization two years before the start of the study and those who rated their general health as poor were excluded. Results: Among manual workers and lower-level employees the risk of CHD was significantly higher than among middle-level employees and professionals (49% and 50%, respectively), after adjustment for age and sex. The association between low socioeconomic status and increased CHD risk disappeared after adjustment for the CHD risk factors, which were more prevalent among those with low socioeconomic status. All the CHD risk factors (with the exception of BMI) were associated with increased CHD incidence rates. Conclusions: Low socioeconomic status remains a significant predictor of CHD among people aged ≥65 years. Healthcare policies among elderly patients should encourage physical activity and smoking cessation in all socioeconomic groups.
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| 23. |
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| 24. |
- Sundquist, K, et al.
(författare)
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Increasing trends of obesity in Sweden between 1996/97 and 2000/01
- 2004
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Ingår i: International journal of obesity and related metabolic disorders : journal of the International Association for the Study of Obesity. - : Springer Science and Business Media LLC. - 0307-0565. ; 28:2, s. 254-261
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Tidskriftsartikel (refereegranskat)
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| 25. |
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| 26. |
- Clack, Christopher T. M., et al.
(författare)
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Evaluation of a proposal for reliable low-cost grid power with 100% wind, water, and solar
- 2017
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Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : NATL ACAD SCIENCES. - 0027-8424 .- 1091-6490. ; 114:26, s. 6722-6727
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Tidskriftsartikel (refereegranskat)abstract
- A number of analyses, meta-analyses, and assessments, including those performed by the Intergovernmental Panel on Climate Change, the National Oceanic and Atmospheric Administration, the National Renewable Energy Laboratory, and the International Energy Agency, have concluded that deployment of a diverse portfolio of clean energy technologies makes a transition to a low-carbon-emission energy system both more feasible and less costly than other pathways. In contrast, Jacobson et al. [Jacobson MZ, Delucchi MA, Cameron MA, Frew BA (2015) Proc Natl Acad Sci USA 112(49): 15060-15065] argue that it is feasible to provide "low-cost solutions to the grid reliability problem with 100% penetration of WWS [wind, water and solar power] across all energy sectors in the continental United States between 2050 and 2055", with only electricity and hydrogen as energy carriers. In this paper, we evaluate that study and find significant shortcomings in the analysis. In particular, we point out that this work used invalid modeling tools, contained modeling errors, and made implausible and inadequately supported assumptions. Policy makers should treat with caution any visions of a rapid, reliable, and low-cost transition to entire energy systems that relies almost exclusively on wind, solar, and hydroelectric power.
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| 27. |
- Fellows, Jeffrey L., et al.
(författare)
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Dentist and practice characteristics associated with restorative treatment of enamel caries in permanent teeth : Multiple-regression modeling of observational clinical data from The National Dental PBRN
- 2014
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Ingår i: American Journal of Dentistry. - 0894-8275. ; 27:2, s. 91-99
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: Current evidence in dentistry recommends non-surgical treatment to manage enamel caries lesions. However, surveyed practitioners report they would restore enamel lesions that are confined to the enamel. Actual clinical data were used to evaluate patient, dentist, and practice characteristics associated with restoration of enamel caries, while accounting for other factors. Methods: Data from a National Dental Practice-Based Research Network observational study of consecutive restorations placed in previously unrestored permanent tooth surfaces and practice/demographic data from 229 participating network dentists were combined. ANOVA and logistic regression, using generalized estimating equations (GEE) and variable selection within blocks, were used to test the hypothesis that patient, dentist, and practice characteristics were associated with variations in enamel restorations of occlusal and proximal caries compared to dentin lesions, accounting for dentist and patient clustering. Results: Network dentists from five regions placed 6,891 restorations involving occlusal and/or proximal caries lesions. Enamel restorations accounted for 16% of enrolled occlusal caries lesions and 6% of enrolled proximal caries lesions. Enamel occlusal restorations varied significantly (P< 0.05) by patient age and race/ethnicity, dentists' use of caries risk assessment, network region, and practice type. Enamel proximal restorations varied significantly (P< 0.05) by dentist race/ethnicity, network region, and practice type.
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| 28. |
- Frazer, D., et al.
(författare)
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Degradation of HT9 under simultaneous ion beam irradiation and liquid metal corrosion
- 2016
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Ingår i: Journal of Nuclear Materials. - : Elsevier BV. - 0022-3115 .- 1873-4820. ; 479, s. 382-389
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Tidskriftsartikel (refereegranskat)abstract
- A potentially promising coolant/structural material pair for a liquid-metal-cooled fast reactors is lead bismuth eutectic (LBE) coolant with the ferritic/martensitic steel HT9. The challenge of deploying LBE, however, is the corrosive environment it creates for structural materials. This corrosion can be mitigated with precise oxygen content control in the LBE to allow for the growth of passive protective oxide layers on the surface of the steel. In this paper, results are reported from the Irradiation Corrosion Experiment II (ICE-II), which allowed the simultaneous irradiation of a sample while in contact with LBE. It was found that a characteristic multilayer structure with an outer Fe3O4 oxide and inner FeCr2O4 spinel was grown and the oxidation was significantly larger in the irradiated region when compared to the region that was only exposed to LBE corrosion. Possible mechanisms are discussed to help understand this irradiation enhanced corrosion behavior.
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| 29. |
- Frisch, M, et al.
(författare)
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Cultural bias in the AAP's 2012 Technical Report and Policy Statement on male circumcision
- 2013
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Ingår i: Pediatrics. - : American Academy of Pediatrics (AAP). - 1098-4275 .- 0031-4005. ; 131:4, s. 796-800
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Tidskriftsartikel (refereegranskat)abstract
- The American Academy of Pediatrics recently released its new Technical Report and Policy Statement on male circumcision, concluding that current evidence indicates that the health benefits of newborn male circumcision outweigh the risks. The technical report is based on the scrutiny of a large number of complex scientific articles. Therefore, while striving for objectivity, the conclusions drawn by the 8 task force members reflect what these individual physicians perceived as trustworthy evidence. Seen from the outside, cultural bias reflecting the normality of nontherapeutic male circumcision in the United States seems obvious, and the report’s conclusions are different from those reached by physicians in other parts of the Western world, including Europe, Canada, and Australia. In this commentary, a different view is presented by non–US-based physicians and representatives of general medical associations and societies for pediatrics, pediatric surgery, and pediatric urology in Northern Europe. To these authors, only 1 of the arguments put forward by the American Academy of Pediatrics has some theoretical relevance in relation to infant male circumcision; namely, the possible protection against urinary tract infections in infant boys, which can easily be treated with antibiotics without tissue loss. The other claimed health benefits, including protection against HIV/AIDS, genital herpes, genital warts, and penile cancer, are questionable, weak, and likely to have little public health relevance in a Western context, and they do not represent compelling reasons for surgery before boys are old enough to decide for themselves.
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| 30. |
- Frobel, Anne-Kristina, et al.
(författare)
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A time-to-event model for acute rejections in paediatric renal transplant recipients treated with ciclosporin A
- 2013
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Ingår i: British Journal of Clinical Pharmacology. - : Wiley. - 0306-5251 .- 1365-2125. ; 76:4 SI, s. 603-615
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Tidskriftsartikel (refereegranskat)abstract
- AimsCiclosporin A (CsA) dosing in immunosuppression after paediatric kidney transplantation remains challenging, and appropriate target CsA exposures (AUCs) are controversial. This study aimed to develop a time-to-first-acute rejection (AR) model and to explore predictive factors for therapy outcome. MethodsPatient records at the Children's Hospital in Helsinki, Finland, were analysed. A parametric survival model in NONMEM was used to describe the time to first AR. The influences of AUC and other covariates were explored using stepwise covariate modelling, bootstrap-stepwise covariate modelling and cross-validated stepwise covariate modelling. The clinical relevance of the effects was assessed with the time at which 90% of the patients were AR free (t(90)). ResultsData from 87 patients (0.7-19.8 years old, 54 experiencing an AR) were analysed. The baseline hazard was described with a function changing in steps over time. No statistically significant covariate effects were identified, a finding substantiated by all methods used. Thus, within the observed AUC range (90% interval 1.13-8.40hmgl(-1)), a rise in AUC was not found to increase protection from AR. Dialysis time, sex and baseline weight were potential covariates, but the predicted clinical relevance of their effects was low. For the strongest covariate, dialysis time, median t(90) was 5.8days (90% confidence interval 5.1-6.8) for long dialysis times (90th percentile) and 7.4days (6.4-11.7) for short dialysis times (10th percentile). ConclusionsA survival model with discrete time-varying hazards described the data. Within the observed range, AUC was not identified as a covariate. This feedback on clinical practice may help to avoid unnecessarily high CsA dosing in children.
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| 31. |
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| 32. |
- Kersten, CM, et al.
(författare)
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The Management of Asymptomatic Congenital Pulmonary Airway Malformation: Results of a European Delphi Survey
- 2022
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Ingår i: Children (Basel, Switzerland). - : MDPI AG. - 2227-9067. ; 9:8
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Tidskriftsartikel (refereegranskat)abstract
- Consensus on the optimal management of asymptomatic congenital pulmonary airway malformation (CPAM) is lacking, and comparison between studies remains difficult due to a large variety in outcome measures. We aimed to define a core outcome set (COS) for pediatric patients with an asymptomatic CPAM. An online, three-round Delphi survey was conducted in two stakeholder groups of specialized caregivers (surgeons and non-surgeons) in various European centers. Proposed outcome parameters were scored according to level of importance, and the final COS was established through consensus. A total of 55 participants (33 surgeons, 22 non-surgeons) from 28 centers in 13 European countries completed the three rounds and rated 43 outcome parameters. The final COS comprises seven outcome parameters: respiratory insufficiency, surgical complications, mass effect/mediastinal shift (at three time-points) and multifocal disease (at two time-points). The seven outcome parameters included in the final COS reflect the diversity in priorities among this large group of European participants. However, we recommend the incorporation of these outcome parameters in the design of future studies, as they describe measurable and validated outcomes as well as the accepted age at measurement.
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| 33. |
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| 34. |
- Le Guen, Yann, et al.
(författare)
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Multiancestry analysis of the HLA locus in Alzheimer's and Parkinson's diseases uncovers a shared adaptive immune response mediated by HLA-DRB1*04 subtypes.
- 2023
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Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences (PNAS). - 1091-6490 .- 0027-8424. ; 120:36
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Tidskriftsartikel (refereegranskat)abstract
- Across multiancestry groups, we analyzed Human Leukocyte Antigen (HLA) associations in over 176,000 individuals with Parkinson's disease (PD) and Alzheimer's disease (AD) versus controls. We demonstrate that the two diseases share the same protective association at the HLA locus. HLA-specific fine-mapping showed that hierarchical protective effects of HLA-DRB1*04 subtypes best accounted for the association, strongest with HLA-DRB1*04:04 and HLA-DRB1*04:07, and intermediary with HLA-DRB1*04:01 and HLA-DRB1*04:03. The same signal was associated with decreased neurofibrillary tangles in postmortem brains and was associated with reduced tau levels in cerebrospinal fluid and to a lower extent with increased Aβ42. Protective HLA-DRB1*04 subtypes strongly bound the aggregation-prone tau PHF6 sequence, however only when acetylated at a lysine (K311), a common posttranslational modification central to tau aggregation. An HLA-DRB1*04-mediated adaptive immune response decreases PD and AD risks, potentially by acting against tau, offering the possibility of therapeutic avenues.
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| 35. |
- Lind, Marcus, 1976, et al.
(författare)
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Fast-Acting Insulin Aspart in Patients with Type 1 Diabetes in Real-World Clinical Practice: A Noninterventional, Retrospective Chart and Database Study
- 2023
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Ingår i: Diabetes Therapy. - : Springer. - 1869-6953 .- 1869-6961. ; 14, s. 1563-1575
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Tidskriftsartikel (refereegranskat)abstract
- IntroductionThis study utilized continuous glucose monitoring data to analyze the effects of switching to treatment with fast-acting insulin aspart (faster aspart) in adults with type 1 diabetes (T1D) in clinical practice.MethodsA noninterventional database review was conducted in Sweden among adults with T1D using multiple daily injection (MDI) regimens who had switched to treatment with faster aspart as part of basal-bolus treatment. Glycemic data were retrospectively collected during the 26 weeks before switching (baseline) and up to 32 weeks after switching (follow-up) to assess changes in time in glycemic range (TIR; 70-180 mg/dL), mean sensor glucose, glycated hemoglobin (HbA1c) levels, coefficient of variation, time in hyperglycemia (level 1, > 180 to & LE; 250 mg/dL; level 2, > 250 mg/dL), and time in hypoglycemia (level 1, & GE; 54 to < 70 mg/dL; level 2, < 54 mg/dL) (ClinicalTrials.gov Identifier NCT03895515).ResultsOverall, 178 participants were included in the study cohort. The analysis population included 82 individuals (mean age 48.5 years) with adequate glucose sensor data. From baseline to follow-up, statistically significant improvements were reported for TIR (mean increase 3.3%-points [approximately 48 min/day]; p = 0.006) with clinically relevant improvement (& GE; 5%) in 43% of participants. Statistically significant improvements from baseline were observed for mean sensor glucose levels, HbA1c levels, and time in hyperglycemia (levels 1 and 2), with no statistically significant changes in time spent in hypoglycemia.ConclusionsSwitching to faster aspart was associated with improvements in glycemic control without increasing hypoglycemia in adults with T1D using MDI in this real-world setting.
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| 36. |
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| 37. |
- Lissner, Lauren, 1956, et al.
(författare)
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Social mapping of the obesity epidemic in Sweden
- 2000
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Ingår i: International Journal of Obesity and Related Metabolic Disorders. ; 24, s. 801-805
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Tidskriftsartikel (refereegranskat)abstract
- Department of Internal Medicine, Göteborg University, Sweden. lauren.lissner@medfak.gu.se OBJECTIVE: The aim of the present study is to describe the evolution of the obesity epidemic in Sweden, with specific attention to the socioeconomic gradient. DESIGN: Data from the Swedish Surveys of Living Conditions were used. Three such surveys were undertaken in 1980/81, 1988/89, and 1996/97, each of which was based on a simple random sample from the national population registry. SUBJECTS: A total of 38,284 observations are used in this analysis, including males and females aged 16-84. The sample is approximately equally divided among the 3 survey periods and by gender. MEASUREMENTS: The following body weight categories are used to describe changing prevalences: overweight (BMI>/=25), obesity (BMI>/=30) and underweight (BMI<18.5). Because body weight and heights were self-reported, recorded values were adjusted for estimating gender-specific obesity prevalences. Education was used as a proxy for socioeconomic status. RESULTS AND CONCLUSIONS: The prevalence of BMI>/=30 increased significantly over the 16-year observation period. At the time of the 1980/81 survey, the adjusted estimates were 8.8% in women and 6.6% in men, compared to 11.9% and 10.0% respectively, in 1996/97. The prevalence of BMI>/=25 was also analyzed for time trends, with specific attention to populations at risk. The largest proportionate changes occurred in women aged 16-44, among whom the prevalence of overweight doubled. The inverse educational gradient with respect to obesity is still present in both sexes, but there is no indication that it has increased in magnitude between 1980/81-1996/97. PMID: 10878690 [PubMed - indexed for MEDLINE]
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| 38. |
- Lissner, L, et al.
(författare)
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Social mapping of the obesity epidemic in Sweden
- 2000
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Ingår i: International journal of obesity and related metabolic disorders : journal of the International Association for the Study of Obesity. - : Springer Science and Business Media LLC. - 0307-0565. ; 24:6, s. 801-805
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Tidskriftsartikel (refereegranskat)
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| 39. |
- Luo, Jiao, et al.
(författare)
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Genetic Associations Between Modifiable Risk Factors and Alzheimer Disease
- 2023
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Ingår i: JAMA Network Open. - : American Medical Association (AMA). - 2574-3805. ; 6:5
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Tidskriftsartikel (refereegranskat)abstract
- IMPORTANCE An estimated 40% of dementia is potentially preventable by modifying 12 risk factors throughout the life course. However, robust evidence for most of these risk factors is lacking. Effective interventions should target risk factors in the causal pathway to dementia.OBJECTIVE To comprehensively disentangle potentially causal aspects of modifiable risk factors for Alzheimer disease (AD) to inspire new drug targeting and improved prevention.DESIGN, SETTING, AND PARTICIPANTS This genetic association study was conducted using 2-sample univariable and multivariable mendelian randomization. Independent genetic variants associated with modifiable risk factors were selected as instrumental variables from genomic consortia. Outcome data for AD were obtained from the European Alzheimer & Dementia Biobank (EADB), generated on August 31, 2021. Main analyses were conducted using the EADB clinically diagnosed end point data. All analyses were performed between April 12 and October 27, 2022.EXPOSURES Genetically determined modifiable risk factors. MAIN OUTCOMES AND MEASURES Odds ratios (ORs) and 95% CIs for AD were calculated per 1-unit change of genetically determined risk factors.RESULTS The EADB-diagnosed cohort included 39106 participants with clinically diagnosed AD and 401577 control participants without AD. The mean age ranged from 72 to 83 years for participants with AD and 51 to 80 years for control participants. Among participants with AD, 54% to 75% were female, and among control participants, 48% to 60% were female. Genetically determined high-density lipoprotein (HDL) cholesterol concentrations were associated with increased odds of AD (OR per 1-SD increase, 1.10 [95% CI, 1.05-1.16]). Genetically determined high systolic blood pressure was associated with increased risk of AD after adjusting for diastolic blood pressure (OR per 10-mm Hg increase, 1.22 [95% CI, 1.02-1.46]). In a second analysis to minimize bias due to sample overlap, the entire UK Biobank was excluded from the EADB consortium; odds for AD were similar for HDL cholesterol (OR per 1-SD unit increase, 1.08 [95% CI, 1.02-1.15]) and systolic blood pressure after adjusting for diastolic blood pressure (OR per 10-mm Hg increase, 1.23 [95% CI, 1.01-1.50]).CONCLUSIONS AND RELEVANCE This genetic association study found novel genetic associations between high HDL cholesterol concentrations and high systolic blood pressure with higher risk of AD. These findings may inspire new drug targeting and improved prevention implementation.
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| 40. |
- Qvist, J, et al.
(författare)
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Multivariate analyses of mortality from coronary heart disease due to biological and behavioural factors
- 1996
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Ingår i: Scandinavian journal of social medicine. - : SAGE Publications. - 0300-8037. ; 24:1, s. 67-76
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Tidskriftsartikel (refereegranskat)abstract
- Due to affluence and a sedentary life style a great deal of people in the western countries are affected by coronary heart disease (CHD). The relation between CHD and certain risk factors pertaining to life style is evaluated in this study. A primary purpose is to study certain crucial risk factors for women. The main variables are age, smoking, overweight (measured by BMI), blood pressure and exercise. This prospective study is based on self-reported data from the nation-wide Swedish Level of Living Survey and on data from the national Cause of Death Register. The data were analysed separately by sex using a proportional hazards model. The sample was divided into two strata: those with heart disease and/or diabetes initially, and all the rest. A sample of 2546 men and 2760 women between 45 and 74 years of age was followed from 1980 to the end of 1990. During this period 189 men and 75 women died of coronary heart disease (CHD). It was found that high blood pressure raised the relative risk (RR) of death from CHD by almost 60% in both men and women. Male smokers (< 14 cigarettes a day) had about 60% (significant) and female smokers (< 10 cigarettes a day) 150% (significant) excessive mortality from CHD. Different levels of overweight among women were strongly related to excess mortality from CHD, ranging between 100 and 300%. Among men there was no such relation. Lack of physical activity showed only a weak (non-significant) increased risk of death due to CHD. Diabetes was also found to be an important risk factor for mortality from CHD, especially among women, being seven times as high as among non diabetics. A test of sex differences revealed that there were two significant interactions, namely between sex and overweight, and between sex and age. Background variables in relation to mortality from all cardiovascular diseases (CVD) were also studied. There were of course many similarities between the effects of the background variables in both the disease groups, but there were interesting differences too, e.g. overweight turned out to be a significant risk factor also for men and physical inactivity for women.
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| 42. |
- Sperling, L., et al.
(författare)
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Detection of chromosomal abnormalities, congenital abnormalities and transfusion syndrome in twins
- 2007
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Ingår i: Ultrasound in Obstetrics & Gynecology. - : Wiley. - 1469-0705 .- 0960-7692. ; 29:5, s. 517-526
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Tidskriftsartikel (refereegranskat)abstract
- Objective To evaluate the outcome of screening for structural malformations in twins and the outcome of screening for twin-twin transfusion syndrome (TTTS) among monochorionic twins through a number of ultrasound scans from 12 weeks' gestation. Methods Enrolled into this prospective multicenter observational study were women with twin pregnancies diagnosed before 14 + 6 gestational weeks. The monochorionic pregnancies were scanned every second week until 23 weeks in order to rule out early TTTS. All pregnancies had an anomaly scan in week 19 and fetal echocardiography in week 21 that was performed by specialists in fetal echocardiography. Zygosity was determined by DNA analysis in all twin pairs with the same sex. Results Among the 495 pregnancies the prenatal detection rate for severe structural abnormalities including chromosomal aneuploidies was 83% by the combination of a first-trimester nuchal translucency scan and the anomaly scan in week 19. The incidence of severe structural abnormalities was 2.6% and two-thirds of these anomalies were cardiac. There was no significant difference between the incidence in monozygotic and dizygotic twins, nor between twins conceived naturally or those conceived by assisted reproduction. The incidence of TTTS was 23% from 12 weeks until delivery, and all those monochorionic twin pregnancies that miscarried had signs of TTTS. Conclusion Twin pregnancies have an increased risk of congenital malformations and one out of four monochorionic pregnancies develops TTTS. Ultrasound screening to assess chorionicity and follow-up of monochorionic pregnancies to detect signs of TTTS, as well as malformation screening, are therefore essential in the antenatal care of twin pregnancies. Copyright (c) 2007 IS UOG. Published by John Wiley & Sons, Ltd.
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| 43. |
- Sperling, L, et al.
(författare)
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How to identify twins at low risk of spontaneous preterm delivery
- 2005
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Ingår i: Ultrasound in Obstetrics & Gynecology. - : Wiley. - 1469-0705 .- 0960-7692. ; 26:2, s. 138-144
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Tidskriftsartikel (refereegranskat)abstract
- Objective The aim of this study was to evaluate transvaginal sonograpbic assessment of cervical length at 23 weeks as a screening test for spontaneous preterm delivery in order to define a cut-off value that could be used to select twin pregnancies at low risk of spontaneous preterm delivery. Methods In a prospective multicenter study of 383 twin pregnancies included before 14 + 6 weeks a cervical scan with measurement of the cervical length was performed at 23 weeks' gestation. The results were blinded for the clinicians if the cervical length was >= 15 mm. The rates of spontaneous delivery at different cut-off levels of cervical length were determined. Results Eighty-nine percent of the twins had dichorionic placentation and 58% were conceived after assisted reproduction. The rate of spontaneous preterm delivery was 2.3% (1.5% for dichorionic (DC) and 9.1% for (MC) monochorionic twins) before 28 weeks and 18.5% (17.1% for DC and 29.5% for MC twins) before 35 weeks. The screen-positive rate was 5% for a cervical length <= 20, 7-8% at <= 25, 16-17% at <= 30 and 34-48% at <= 35mm depending on chorionicity. The false-negative rate (1 - negative predictive value) ranged from 1.2% at 28 weeks to 18.6% at 35 weeks for all twins. Receiver-operating characteristics curves showed that the sensitivity increased with declining gestation I age with cut-off levels of highest accuracy at 21 mm for 28 weeks and 29 mm for 33 weeks. Conclusions Cervical length measurement at 23 weeks of gestation is a good screening test for predicting twins at low risk of preterm and very preterm delivery, especially in DC twins. The present results suggest that a cut-off of 25 mm should be recommended.
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| 44. |
- Sperling, L., et al.
(författare)
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Naturally conceived twins with monochorionic placentation have the highest risk of fetal loss
- 2006
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Ingår i: Ultrasound in Obstetrics & Gynecology. - : Wiley. - 1469-0705 .- 0960-7692. ; 28:5, s. 644-652
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Tidskriftsartikel (refereegranskat)abstract
- Objective The aim of this study was to estimate the rate of fetal loss in dichorionic (DC) and monochorionic (MC) twin pregnancies stratified according to zygosity and method of conception. Methods In a prospective multicenter observational study women with a twin pregnancy bad an ultrasound scan before 14 + 6 weeks' gestation in order to determine chorionicity. The fetal loss rate, the perinatal, neonatal and infant mortality rates and the frequency of very preterm labor were estimated for the different types of twin. Results Among the 495 pregnancies (421 DC and 74 MC) 229 (46%) were conceived naturally and 266 (54%) by assisted reproduction (AR). Outcome data for 945 liveborn babies were obtained. The spontaneous miscarriage rate before 24 weeks' gestation was 10.9% (7164) among naturally conceived MC compared to 3.0% (51165) for naturally conceived DC twins (P < 0.05). For twins conceived by AR the corresponding figures were 0% (0/10) and 0.4% (1/256). The odds ratio (OR) for very preterm birth - before 28 weeks'gestation - was 4.2 for MC twins compared to DC twins. The relative risk of fetal loss or death among DC twins was 20% of the risk for MC twins. Conclusion The risk of fetal loss, very preterm delivery and neonatal/infant death is significantly higher among twins with MC compared to DC placentation. Twins conceived by AR have a much lower risk of MC placentation. The risk of losing one or both twins seems higher among naturally conceived twins compared to twins conceived by AR, despite the fact that the maternal age was higher among the mothers of the AR twins. Copyright (c) 2006 ISUOG. Published by John Wiley & Sons, Ltd.
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| 45. |
- Svensson, Emma, et al.
(författare)
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The Effect of Botulinum Toxin Type A Injections on Stricture Formation, Leakage Rates, Esophageal Elongation, and Anastomotic Healing Following Primary Anastomosis in a Long- and Short-Gap Esophageal Atresia Model : A Protocol for a Randomized, Controlled, Blinded Trial in Pigs
- 2021
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Ingår i: International Journal of Surgery Protocols. - : IJS Press. - 2468-3574. ; 25:1, s. 171-177
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Tidskriftsartikel (refereegranskat)abstract
- Background:Esophageal atresia (EA) is a congenital malformation affecting 1:3000-4500 newborns. Approximately 15% have a long-gap EA (LGEA), in which case a primary anastomosis is often impossible to achieve. To create continuity of the esophagus patients instead have to undergo lengthening procedures or organ interpositions; methods associated with high morbidity and poor functional outcomes. Esophageal injections of Botulinum Toxin Type A (BTX-A) could enable primary anastomosis and mitigate stricture formation through decreased tissue tension.Methods and Analysis:In this randomized controlled blinded animal trial, 24 pigs are divided into a long- or short-gap EA group (LGEA and SGEA, respectively) and randomized to receive BTX-A or isotonic saline injections. In the LGEA group, injections are given endoscopically in the esophageal musculature. After seven days, a 3 cm esophageal resection and primary anastomosis is performed. In the SGEA group, a 1 cm esophageal resection and primary anastomosis is performed, followed by intraoperative injections of BTX-A or isotonic saline. After 14 days, stricture formation, presence of leakage, and esophageal compliance is assessed using endoscopic and manometric techniques, and in vivo and ex vivo contrast radiography. Tissue elongation is evaluated in a stretch-tension test, and the esophagus is assessed histologically to evaluate anastomotic healing.Ethics and Dissemination:The study complies with the ARRIVE guidelines for animal studies and has been approved by the Danish Animal Experimentation Council. Results will be published in peer-reviewed journals and presented at national and international conferences.
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