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Sökning: WFRF:(Palsson D.)

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1.
  • Clark, DW, et al. (författare)
  • Associations of autozygosity with a broad range of human phenotypes
  • 2019
  • Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 10:1, s. 4957-
  • Tidskriftsartikel (refereegranskat)abstract
    • In many species, the offspring of related parents suffer reduced reproductive success, a phenomenon known as inbreeding depression. In humans, the importance of this effect has remained unclear, partly because reproduction between close relatives is both rare and frequently associated with confounding social factors. Here, using genomic inbreeding coefficients (FROH) for >1.4 million individuals, we show that FROH is significantly associated (p < 0.0005) with apparently deleterious changes in 32 out of 100 traits analysed. These changes are associated with runs of homozygosity (ROH), but not with common variant homozygosity, suggesting that genetic variants associated with inbreeding depression are predominantly rare. The effect on fertility is striking: FROH equivalent to the offspring of first cousins is associated with a 55% decrease [95% CI 44–66%] in the odds of having children. Finally, the effects of FROH are confirmed within full-sibling pairs, where the variation in FROH is independent of all environmental confounding.
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2.
  • Thiele, I., et al. (författare)
  • A community-driven global reconstruction of human metabolism
  • 2013
  • Ingår i: Nature Biotechnology. - : Springer Science and Business Media LLC. - 1087-0156 .- 1546-1696. ; 31:5, s. 419-
  • Tidskriftsartikel (refereegranskat)abstract
    • Multiple models of human metabolism have been reconstructed, but each represents only a subset of our knowledge. Here we describe Recon 2, a community-driven, consensus 'metabolic reconstruction', which is the most comprehensive representation of human metabolism that is applicable to computational modeling. Compared with its predecessors, the reconstruction has improved topological and functional features, including similar to 2x more reactions and similar to 1.7x more unique metabolites. Using Recon 2 we predicted changes in metabolite biomarkers for 49 inborn errors of metabolism with 77% accuracy when compared to experimental data. Mapping metabolomic data and drug information onto Recon 2 demonstrates its potential for integrating and analyzing diverse data types. Using protein expression data, we automatically generated a compendium of 65 cell type-specific models, providing a basis for manual curation or investigation of cell-specific metabolic properties. Recon 2 will facilitate many future biomedical studies and is freely available at http://humanmetabolism.org/.
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3.
  • Estrada, Karol, et al. (författare)
  • Genome-wide meta-analysis identifies 56 bone mineral density loci and reveals 14 loci associated with risk of fracture.
  • 2012
  • Ingår i: Nature genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 44:5, s. 491-501
  • Tidskriftsartikel (refereegranskat)abstract
    • Bone mineral density (BMD) is the most widely used predictor of fracture risk. We performed the largest meta-analysis to date on lumbar spine and femoral neck BMD, including 17 genome-wide association studies and 32,961 individuals of European and east Asian ancestry. We tested the top BMD-associated markers for replication in 50,933 independent subjects and for association with risk of low-trauma fracture in 31,016 individuals with a history of fracture (cases) and 102,444 controls. We identified 56 loci (32 new) associated with BMD at genome-wide significance (P < 5 × 10(-8)). Several of these factors cluster within the RANK-RANKL-OPG, mesenchymal stem cell differentiation, endochondral ossification and Wnt signaling pathways. However, we also discovered loci that were localized to genes not known to have a role in bone biology. Fourteen BMD-associated loci were also associated with fracture risk (P < 5 × 10(-4), Bonferroni corrected), of which six reached P < 5 × 10(-8), including at 18p11.21 (FAM210A), 7q21.3 (SLC25A13), 11q13.2 (LRP5), 4q22.1 (MEPE), 2p16.2 (SPTBN1) and 10q21.1 (DKK1). These findings shed light on the genetic architecture and pathophysiological mechanisms underlying BMD variation and fracture susceptibility.
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4.
  • Sperber, A. D., et al. (författare)
  • Face-to-face interviews versus Internet surveys: Comparison of two data collection methods in the Rome foundation global epidemiology study: Implications for population-based research
  • 2023
  • Ingår i: Neurogastroenterology and Motility. - 1350-1925. ; 35:6
  • Tidskriftsartikel (refereegranskat)abstract
    • Background and AimsThe Rome Foundation Global Epidemiology Study (RFGES) assessed the prevalence, burden, and associated factors of Disorders of Gut-Brain Interaction (DGBI) in 33 countries around the world. Achieving worldwide sampling necessitated use of two different surveying methods: In-person household interviews (9 countries) and Internet surveys (26 countries). Two countries, China and Turkey, were surveyed with both methods. This paper examines the differences in the survey results with the two methods, as well as likely reasons for those differences. MethodsThe two RFGES survey methods are described in detail, and differences in DGBI findings summarized for household versus Internet surveys globally, and in more detail for China and Turkey. Logistic regression analysis was used to elucidate factors contributing to these differences. ResultsOverall, DGBI were only half as prevalent when assessed with household vs Internet surveys. Similar patterns of methodology-related DGBI differences were seen within both China and Turkey, but prevalence differences between the survey methods were dramatically larger in Turkey. No clear reasons for outcome differences by survey method were identified, although greater relative reduction in bowel and anorectal versus upper gastrointestinal disorders when household versus Internet surveying was used suggests an inhibiting influence of social sensitivity. ConclusionsThe findings strongly indicate that besides affecting data quality, manpower needs and data collection time and costs, the choice of survey method is a substantial determinant of symptom reporting and DGBI prevalence outcomes. This has important implications for future DGBI research and epidemiological research more broadly.
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5.
  • Wuttke, Matthias, et al. (författare)
  • A catalog of genetic loci associated with kidney function from analyses of a million individuals
  • 2019
  • Ingår i: Nature Genetics. - : NATURE PUBLISHING GROUP. - 1061-4036 .- 1546-1718. ; 51:6, s. 957-972
  • Tidskriftsartikel (refereegranskat)abstract
    • Chronic kidney disease (CKD) is responsible for a public health burden with multi-systemic complications. Through transancestry meta-analysis of genome-wide association studies of estimated glomerular filtration rate (eGFR) and independent replication (n = 1,046,070), we identified 264 associated loci (166 new). Of these,147 were likely to be relevant for kidney function on the basis of associations with the alternative kidney function marker blood urea nitrogen (n = 416,178). Pathway and enrichment analyses, including mouse models with renal phenotypes, support the kidney as the main target organ. A genetic risk score for lower eGFR was associated with clinically diagnosed CKD in 452,264 independent individuals. Colocalization analyses of associations with eGFR among 783,978 European-ancestry individuals and gene expression across 46 human tissues, including tubulo-interstitial and glomerular kidney compartments, identified 17 genes differentially expressed in kidney. Fine-mapping highlighted missense driver variants in 11 genes and kidney-specific regulatory variants. These results provide a comprehensive priority list of molecular targets for translational research.
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7.
  • Kiemeney, Lambertus A, et al. (författare)
  • A sequence variant at 4p16.3 confers susceptibility to urinary bladder cancer.
  • 2010
  • Ingår i: Nature genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 42:5, s. 415-9
  • Tidskriftsartikel (refereegranskat)abstract
    • Previously, we reported germline DNA variants associated with risk of urinary bladder cancer (UBC) in Dutch and Icelandic subjects. Here we expanded the Icelandic sample set and tested the top 20 markers from the combined analysis in several European case-control sample sets, with a total of 4,739 cases and 45,549 controls. The T allele of rs798766 on 4p16.3 was found to associate with UBC (odds ratio = 1.24, P = 9.9 x 10(-12)). rs798766 is located in an intron of TACC3, 70 kb from FGFR3, which often harbors activating somatic mutations in low-grade, noninvasive UBC. Notably, rs798766[T] shows stronger association with low-grade and low-stage UBC than with more aggressive forms of the disease and is associated with higher risk of recurrence in low-grade stage Ta tumors. The frequency of rs798766[T] is higher in Ta tumors that carry an activating mutation in FGFR3 than in Ta tumors with wild-type FGFR3. Our results show a link between germline variants, somatic mutations of FGFR3 and risk of UBC.
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8.
  • Sperber, A. D., et al. (författare)
  • Greater Overlap of Rome IV Disorders of Gut-Brain Interactions Leads to Increased Disease Severity and Poorer Quality of Life
  • 2022
  • Ingår i: Clinical Gastroenterology and Hepatology. - : Elsevier BV. - 1542-3565. ; 20:5
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND AND AIMS: Conditions such as irritable bowel syndrome (IBS), functional dyspepsia, and functional constipation are among the prevalent gastrointestinal (GI) disorders classified as disorders of gutbrain interaction (DGBI), which can adversely affect the lives of sufferers. This study aimed to assess the degree and consequences of overlapping DGBI in a large population-based global scale. METHODS: Internet survey data from 54,127 adults (49.1% women) in 26 countries were analyzed by 4 GI anatomic regions (esophageal, gastroduodenal, bowel, and anorectal). The number of DGBIaffected GI regions was assessed, including associations with sex, age, disease severity, quality of life, psychosocial variables, and health care utilization. RESULTS: A total of 40.3% of surveyed individuals met Rome IV criteria for a DGBI. The percentages with 1-4 DGBI-affected GI regions were 68.3%, 22.3%, 7.1%, and 2.3%, respectively. The IBS symptom severity score increased significantly from 1 (207.6) to 4 (291.6) regions, as did nonGI symptom reporting (somatization), anxiety and depression, concerns and embarrassment about bowel function, doctor visits, medications, and abdominal surgeries (all P <.0001). Quality of life decreased with increasing number of DGBI regions (P <.0001). In a logistic mixed model, non-GI symptoms (odds ratio [OR], 1.09; 95% confidence interval [CI], 1.08-1.10), being very vs not concerned (OR, 2.55; 95% CI, 2.27-2.90), being very vs not embarrassed about bowel function (OR, 1.20; 95% CI, 1.08-1.33), and mean number of doctor visits (OR, 1.23; 95% CI, 1.115-1.32) were most strongly associated with number of DGBI regions. CONCLUSIONS: DGBI in multiple anatomic GI regions is associated with increased psychological comorbidity, health care utilization, and IBS severity. Physician awareness of overlap could improve quality of care, prevent unnecessary interventions, and yield more positive health outcomes.
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9.
  • Sperber, A. D., et al. (författare)
  • Worldwide Prevalence and Burden of Functional Gastrointestinal Disorders, Results of Rome Foundation Global Study
  • 2021
  • Ingår i: Gastroenterology. - : Elsevier BV. - 0016-5085. ; 160:1
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND & AIMS: Although functional gastrointestinal disorders (FGIDs), now called disorders of gut-brain interaction, have major economic effects on health care systems and adversely affect quality of life, little is known about their global prevalence and distribution. We investigated the prevalence of and factors associated with 22 FGIDs, in 33 countries on 6 continents. METHODS: Data were collected via the Internet in 24 countries, personal interviews in 7 countries, and both in 2 countries, using the Rome IV diagnostic questionnaire, Rome III irritable bowel syndrome questions, and 80 items to identify variables associated with FGIDs. Data collection methods differed for Internet and household groups, so data analyses were conducted and reported separately. RESULTS: Among the 73,076 adult respondents (49.5% women), diagnostic criteria were met for at least 1 FGID by 40.3% persons who completed the Internet surveys (95% confidence interval [CI], 39.9-40.7) and 20.7% of persons who completed the household surveys (95% CI, 20.2-21.3). FGIDs were more prevalent among women than men, based on responses to the Internet survey (odds ratio, 1.7; 95% CI, 1.6-1.7) and household survey (odds ratio, 1.3; 95% CI, 1.3-1.4). FGIDs were associated with lower quality of life and more frequent doctor visits. Proportions of subjects with irritable bowel syndrome were lower when the Rome IV criteria were used, compared with the Rome III criteria, in the Internet survey (4.1% vs 10.1%) and household survey (1.5% vs 3.5%). CONCLUSIONS: In a large-scale multinational study, we found that more than 40% of persons worldwide have FGIDs, which affect quality of life and health care use. Although the absolute prevalence was higher among Internet respondents, similar trends and relative distributions were found in people who completed Internet vs personal interviews.
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10.
  • Hreinsson, J. P., et al. (författare)
  • Factor Analysis of the Rome IV Criteria for Major Disorders of Gut-Brain Interaction (DGBI) Globally and Across Geographical, Sex, and Age Groups
  • 2023
  • Ingår i: Gastroenterology. - : Elsevier BV. - 0016-5085. ; 164:7, s. 1211-1222
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND & AIMS: The Rome criteria are widely accepted for diagnosing disorders of gut-brain interaction, but their global applicability has been debated. This study aimed to evaluate the validity of the Rome IV criteria by factor analysis globally, across geographical regions, by sex, and by age groups. METHODS: Data were collected in 26 countries using the Rome IV questionnaire. Forty-nine ordinal variables were used in exploratory factor analysis (EFA) to identify clusters of inter-correlated variables (factors) within the data set. Confirmatory factor analysis with predefined factors of the disorders of gut-brain interaction was compared with the factors in the EFA. Analyses were per-formed globally, for each geographical region (North and Latin America, Western and Eastern Europe, Middle East, Asia), sex, and age groups (18-34, 35-49, 50-64, >65).RESULTS: A total of 54,127 people were included. The EFA identified 10 factors accounting for 57% of the variance: ir-ritable bowel syndrome, constipation, diarrhea, upper gastrointestinal symptoms, globus, regurgitation/retching, chest pain, nausea/vomiting, and 2 right upper quadrant pain factors. Most factors had close correspondence to a Rome IV criteria diagnosis, but notably, functional dysphagia and heartburn symptoms were often included in the same factor and/or in upper gastrointestinal symptoms. Most factors were consistent across geographical regions, sex, and age groups, and compatible to the global results. All prespecified factors in the confirmatory analysis had a loading >0.4, indicating validity of the Rome IV criteria. CONCLUSIONS: The results indicate that the Rome IV criteria for irritable bowel syndrome, functional dyspepsia, functional constipation, globus, and biliary pain are globally valid and represent universal diagnostic entities that are similar across sex and age groups.
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11.
  • Keqi, A., et al. (författare)
  • Electronic structure of the dilute magnetic semiconductor Ga1-xMnxP from hard x-ray photoelectron spectroscopy and angle-resolved photoemission
  • 2018
  • Ingår i: Physical Review B. - 2469-9950 .- 2469-9969. ; 97:15
  • Tidskriftsartikel (refereegranskat)abstract
    • We have investigated the electronic structure of the dilute magnetic semiconductor (DMS) Ga0.98Mn0.02P and compared it to that of an undoped GaP reference sample, using hard x-ray photoelectron spectroscopy (HXPS) and hard x-ray angle-resolved photoemission spectroscopy (HARPES) at energies of about 3 keV. We present experimental data, as well as theoretical calculations, to understand the role of the Mn dopant in the emergence of ferromagnetism in this material. Both core-level spectra and angle-resolved or angle-integrated valence spectra are discussed. In particular, the HARPES experimental data are compared to free-electron final-state model calculations and to more accurate one-step photoemission theory. The experimental results show differences between Ga0.98Mn0.02P and GaP in both angle-resolved and angle-integrated valence spectra. The Ga0.98Mn0.02P bands are broadened due to the presence of Mn impurities that disturb the long-range translational order of the host GaP crystal. Mn-induced changes of the electronic structure are observed over the entire valence band range, including the presence of a distinct impurity band close to the valence-band maximum of the DMS. These experimental results are in good agreement with the one-step photoemission calculations and a prior HARPES study of Ga0.97Mn0.03As and GaAs [Gray et al., Nat. Mater. 11, 957 (2012)], demonstrating the strong similarity between these two materials. The Mn 2p and 3s core-level spectra also reveal an essentially identical state in doping both GaAs and GaP.
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12.
  • Koopman, J J E, et al. (författare)
  • Senescence rates in patients with end-stage renal disease: a critical appraisal of the Gompertz model.
  • 2011
  • Ingår i: Aging Cell. - : Wiley. - 1474-9726 .- 1474-9718. ; Dec, s. 233-238
  • Tidskriftsartikel (refereegranskat)abstract
    • The most frequently used model to describe the exponential increase in mortality rate over age is the Gompertz equation. Logarithmically transformed, the equation conforms to a straight line, of which the slope has been interpreted as the rate of senescence. Earlier, we proposed the derivative function of the Gompertz equation as a superior descriptor of senescence rate. Here, we tested both measures of the rate of senescence in a population of patients with end-stage renal disease. It is clinical dogma that patients on dialysis experience accelerated senescence, whereas those with a functional kidney transplant have mortality rates comparable to the general population. Therefore, we calculated the age-specific mortality rates for European patients on dialysis (n=274,221; follow-up=594,767 person-years), for European patients with a functioning kidney transplant (n=61,286; follow-up=345,024 person-years), and for the general European population. We found higher mortality rates, but a smaller slope of logarithmical mortality curve for patients on dialysis compared to both patients with a functioning kidney transplant and the general population (p<0.001). A classical interpretation of the Gompertz model would imply that the rate of senescence in patients on dialysis is lower than in patients with a functioning transplant and lower than in the general population. In contrast, the derivative function of the Gompertz equation yielded highest senescence rates for patients on dialysis, whereas the rate was similar in patients with a functioning transplant and the general population. We conclude that the rate of senescence is better described by the derivative function of the Gompertz equation.
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13.
  • Palsson, O. S., et al. (författare)
  • Human Milk Oligosaccharides Support Normal Bowel Function and Improve Symptoms of Irritable Bowel Syndrome: A Multicenter, Open-Label Trial
  • 2020
  • Ingår i: Clinical and translational gastroenterology. - : Ovid Technologies (Wolters Kluwer Health). - 2155-384X. ; 11:12
  • Tidskriftsartikel (refereegranskat)abstract
    • INTRODUCTION: Treatment options for irritable bowel syndrome (IBS) are limited, causing many patients to remain symptomatic. This study assessed the potential of human milk oligosaccharides (HMOs) to normalize bowel habits. Secondary outcomes included IBS severity and health-related quality of life. METHODS: This multicenter, open-label trial recruited patients with IBS from 17 sites across the United States. Patients received daily orally administrated 5-g intervention of the HMOs 2'-fucosyllactose and lacto-N-neotetraose in a 4:1 mix. Bowel habits, IBS symptoms, and quality of life were assessed at baseline and every 4 weeks during the 12-week intervention. RESULTS: A total of 317 patients (70.7% women; mean age of 44.0 years, range 18-93 years) received the trial product, and 245 patients completed the trial according to protocol. Patients had a significant improvement from baseline to 12 weeks in total percentage of bowel movements with abnormal stool consistency (mean and [95% confidence interval]: 90.7 [88.9-92.9] vs 57.2% [53.9-60.5], P < 0.0001), overall IBS Symptom Severity Score (323 [314-332] vs 144 [133-155], P < 0.0001) and health-rela,ted quality of life (50.4 [48.0-52.8] vs 74.6 [72.3-76.9], P < 0.0001). Improvement was similar across IBS subtypes. Symptoms improved most in the first 4 weeks of intervention. The most common side effects were mild gastrointestinal symptoms such as flatulence, abdominal pain and discomfort, and distension. DISCUSSION: Supplementation with 2 selected HMOs improves IBS symptoms and quality of life without substantial side effects. These promising results suggest that this novel approach to IBS should be confirmed in a randomized, placebo-controlled trial.
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14.
  • Parker, S., et al. (författare)
  • Functional Gastrointestinal Disorders and Associated Health Impairment in Individuals with Celiac Disease
  • 2022
  • Ingår i: Clinical Gastroenterology and Hepatology. - : Elsevier BV. - 1542-3565. ; 20:6
  • Tidskriftsartikel (refereegranskat)abstract
    • Background & Aims: Individuals with celiac disease (CD) can experience persisting gastrointestinal symptoms despite adhering to a gluten-free diet (GFD). This may be due to functional gastrointestinal disorders (FGIDs), although there is little data on its prevalence and associated factors. Methods: An online health questionnaire was completed by adult members of Celiac UK in October 2018. The survey included validated questions on Rome IV FGIDs, nongastrointestinal somatic symptoms, anxiety, depression, quality of life, health care use, GFD duration, and its adherence using the celiac dietary adherence test score (with a value ≤ 13 indicating optimal adherence). The prevalence of FGIDs and associated health impairment in the celiac cohort was compared against an age- and sex-matched population-based control group. Results: Of the 863 individuals with CD (73% female; mean age, 61 years), all were taking a GFD for at least 1 year, with 96% declaring that they have been on the diet for 2 or more years (2–4 years, 20%; ≥5 years, 76%). The adherence to a GFD was deemed optimal in 61% (n = 523), with the remaining 39% (n = 340) nonadherent. Those adhering to a GFD fulfilled criteria for a FGID in approximately one-half of cases, although this was significantly lower than nonadherent subjects (51% vs 75%; odds ratio [OR], 2.0; P < .001). However, the prevalence of FGIDs in GFD-adherent subjects was significantly higher than in matched population-based controls (35%; OR, 2.0; P < .001). This was accounted for by functional bowel (46% vs 31%; OR, 1.9; P < .0001) and anorectal disorders (14.5% vs 9.3%; OR, 1.7; P = .02) but not functional esophageal (7.6% vs 6.1%; P = .36) or gastroduodenal disorders (8.7% vs 7.4%; P = .47). Finally, GFD-adherent subjects with FGIDs were significantly more likely than their counterparts without FGIDs to have abnormal levels of anxiety (5% vs 2%; OR, 2.8; P = .04), depression (7% vs 2%; OR, 3.6; P = .01), somatization (31% vs 8%; OR, 5.1; P < .0001), and reduced quality of life (P < .0001). Conclusion: One in 2 people with CD, despite having been on a GFD for a number of years and demonstrating optimal adherence, have ongoing symptoms compatible with a Rome IV FGID. This is 2-fold the odds of FGIDs seen in age- and sex-matched controls. The presence of FGIDs is associated with significant health impairment, including psychological comorbidity. Addressing disorders of gut-brain interaction might improve outcomes in this specific group of patients. © 2021 AGA Institute
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15.
  • Tai, F. W. D., et al. (författare)
  • Functional gastrointestinal disorders are increased in joint hypermobility-related disorders with concomitant postural orthostatic tachycardia syndrome
  • 2020
  • Ingår i: Neurogastroenterology and Motility. - : Wiley. - 1350-1925 .- 1365-2982. ; 32:12
  • Tidskriftsartikel (refereegranskat)abstract
    • Background Individuals with hypermobility spectrum disorders/hypermobile Ehlers-Danlos syndrome (HSD/hEDS) frequently fulfill criteria for Rome IV functional gastrointestinal disorders (FGIDs). Postural orthostatic tachycardia syndrome (POTS) is also commonly reported in HSD/hEDS and may impact on co-morbidity with and severity of FGIDs, although this remains to be studied. We determined the impact of concomitant POTS and HSD/hEDS on their association with Rome IV FGIDs. Methods With the help of the charity organization Ehlers-Danlos Support UK, an online cross-sectional health survey was completed by individuals with HSD/hEDS. The survey enquired for (a) self-reported doctor diagnosis of POTS, chronic fatigue syndrome, and fibromyalgia, (b) the presence and symptom frequency of Rome IV FGIDs, and (c) anxiety and depression scores. Key Results Of 616 subjects with HSD/hEDS, 37.5% reported a doctor diagnosis of POTS. POTS-positive individuals were significantly younger than POTS-negative subjects (37 vs 40 years,P = 0.002), more likely to report chronic fatigue syndrome (44% vs 31%,P < 0.0001), and showed a trend toward increased prevalence of fibromyalgia (44% vs 37%,P = 0.06) and higher depression score (P = 0.07). POTS-positive subjects were also more likely to fulfill criteria for Rome IV FGIDs across various organ domains and experienced both upper and lower gastrointestinal symptoms significantly more frequently. The increased associations for FGIDs and GI symptom frequency remained unchanged in HSD/hEDS subjects with POTS following adjustments for age, chronic fatigue syndrome, fibromyalgia, and depression scores. Conclusions and Inferences The high FGID burden in HSD/hEDS is further amplified in the presence of POTS. Future studies should elucidate the mechanism by which POTS arises in HSD/hEDS and is associated with increased GI symptoms.
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16.
  • van Wijk, Xander M., et al. (författare)
  • Whole-Genome Sequencing of Invasion-Resistant Cells Identifies Laminin α2 as a Host Factor for Bacterial Invasion
  • 2017
  • Ingår i: mBio. - : American Society for Microbiology. - 2161-2129 .- 2150-7511. ; 8:1
  • Tidskriftsartikel (refereegranskat)abstract
    • To understand the role of glycosaminoglycans in bacterial cellular invasion, xylosyltransferase-deficient mutants of Chinese hamster ovary (CHO) cells were created using clustered regularly interspaced short palindromic repeat (CRISPR) and CRISPR-associated gene 9 (CRISPR-cas9) gene targeting. When these mutants were compared to the pgsA745 cell line, a CHO xylosyltransferase mutant generated previously using chemical mutagenesis, an unexpected result was obtained. Bacterial invasion of pgsA745 cells by group B Streptococcus (GBS), group A Streptococcus, and Staphylococcus aureus was markedly reduced compared to the invasion of wild-type cells, but newly generated CRISPR-cas9 mutants were only resistant to GBS. Invasion of pgsA745 cells was not restored by transfection with xylosyltransferase, suggesting that an additional mutation conferring panresistance to multiple bacteria was present in pgsA745 cells. Whole-genome sequencing and transcriptome sequencing (RNA-Seq) uncovered a deletion in the gene encoding the laminin subunit alpha 2 (Lama2) that eliminated much of domain L4a. Silencing of the long Lama2 isoform in wild-type cells strongly reduced bacterial invasion, whereas transfection with human LAMA2 cDNA significantly enhanced invasion in pgsA745 cells. The addition of exogenous laminin-alpha 2 beta 1 gamma 1/laminin-alpha 2 beta 2 gamma 1 strongly increased bacterial invasion in CHO cells, as well as in human alveolar basal epithelial and human brain microvascular endothelial cells. Thus, the L4a domain in laminin alpha 2 is important for cellular invasion by a number of bacterial pathogens. IMPORTANCE Pathogenic bacteria penetrate host cellular barriers by attachment to extracellular matrix molecules, such as proteoglycans, laminins, and collagens, leading to invasion of epithelial and endothelial cells. Here, we show that cellular invasion by the human pathogens group B Streptococcus, group A Streptococcus, and Staphylococcus aureus depends on a specific domain of the laminin alpha 2 subunit. This finding may provide new leads for the molecular pathogenesis of these bacteria and the development of novel antimicrobial drugs.
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17.
  • Agustsson, A. S., et al. (författare)
  • Causes of gastrointestinal bleeding in oral anticoagulant users compared to non-users in a population-based study
  • 2022
  • Ingår i: Scandinavian Journal of Gastroenterology. - : Informa UK Limited. - 0036-5521 .- 1502-7708. ; 57:2, s. 239-245
  • Tidskriftsartikel (refereegranskat)abstract
    • Background/aims Causes of gastrointestinal bleeding (GIB) in patients on oral anticoagulants (OACs) are not well established. The aims of the study were to compare the causes of GIB in patients on OACs and those not on OAC therapy. Methods A nationwide study of all GIB events in patients on OACs in Iceland from 2014-2019 was conducted. Bleeding events were obtained through ICD-10 codes and review of endoscopy databases, confirmed by review of medical records. For comparison, patients not on OACs from previous Icelandic population-based studies were used. Results Among 752 GIB events in 12,005 patients on OACs, 273 (1.9%) had verified upper and 391 (2.7%) had verified lower GIB. For lower GIB, multivariate analysis showed that OAC users were more likely to have colonic polyps (OR 6.6, 95% CI: 2.4 - 17.8, p < .001) or colorectal cancer (OR 3.7, 95% CI: 2.0 - 7.0, p < .001) but less likely to have ischemic colitis (OR 0.11, 95% CI: 0.04 - 0.26, p < .001). For upper GIB, bleeding from mucosal erosions (OR 4.0 95% CI: 2.5 - 7.9, p < .001) and angiodysplasia (OR 3.6, 95%CI: 1.5 - 8.6, p = .003) were more common in OAC users. Conclusions A high proportion of GIB caused by colonic polyps and colorectal cancer among OAC patients indicates that OACs treatment may facilitate cancer diagnosis. The low proportion of ischemic colitis among those on OACs suggests that OACs provide a protective effect against ischemic colitis. OACs seem to increase the bleeding from angiodysplasia and mucosal erosive disease.
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18.
  • Aziz, Imran, et al. (författare)
  • Epidemiology, Clinical Characteristics, and Associations for Rome IV Functional Nausea and Vomiting Disorders in Adults
  • 2019
  • Ingår i: Clinical Gastroenterology and Hepatology. - : Elsevier BV. - 1542-3565. ; 17:5, s. 878-886
  • Tidskriftsartikel (refereegranskat)abstract
    • Background & Aims: Functional nausea and vomiting disorders (FNVDs) are classified as chronic nausea and vomiting syndrome (CNVS) or cyclic vomiting syndrome (CVS)—CVS includes cannabinoid hyperemesis syndrome. We investigated the population prevalence of FNVDs, their characteristics, and associated factors. Methods: In the year 2015, an Internet cross-sectional health survey was completed by 5931 adults in the general populations of 3 English-speaking countries; 2100 participants were in the United States, Canada, or the United Kingdom. Quota-based sampling was used to generate demographically balanced and population-representative samples. The survey collected data on demographics, health care visits, medications, somatic symptom severity, quality of life, and symptom-based diagnostic criteria for Rome IV FNVDs as well as for irritable bowel syndrome and functional dyspepsia. Subsequent comparisons were made between Rome IV FNVD subjects and individuals without FNVDs (controls). Results: Overall, 2.2% of the population (n = 131) fulfilled symptom-based diagnostic criteria for Rome IV FNVDs: the United States (3%) had a greater prevalence than Canada (1.9%) or the United Kingdom (1.8%) (P =.02). The prevalence of CNVS was similar among the countries, ranging from 0.8% to 1.2%. However, the prevalence of CVS was higher in the United States (2%) than in Canada (0.7%) or the United Kingdom (1%) (P =.03). The proportion of subjects with CVS taking cannabis did not differ significantly among countries (P =.31), although the 7 cases of cannabinoid hyperemesis syndrome were in the United States. A significantly higher proportion of subjects with CVS reported a compulsive need for hot water bathing to alleviate emetic symptoms than subjects with CNVS (44% vs 19%; P =.03); this behavior was independent of cannabis but augmented by its use. Subjects with FNVDs had significantly greater health impairment and health care utilization than controls. On multivariate analysis, independent factors associated with FNVDs were younger age, increasing somatic symptom severity, lower quality of life, presence of irritable bowel syndrome, and functional dyspepsia. However, on subgroup analysis, somatic symptom severity was associated with CVS but not CNVS, whereas poor quality of life was associated with CNVS but not CVS. Conclusions: Based on a cross-sectional health survey of adults in the general populations of 3 English-speaking countries, approximately 2% of subjects meet symptom-based criteria for Rome IV FNVDs and have considerable health impairments. Hot water bathing to alleviate emetic symptoms is reported for all FNVDs, and is perpetuated by cannabis use. © 2019 AGA Institute
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19.
  • Aziz, Imran, et al. (författare)
  • Epidemiology, clinical characteristics, and associations for symptom-based Rome IV functional dyspepsia in adults in the USA, Canada, and the UK: a cross-sectional population-based study
  • 2018
  • Ingår i: Lancet Gastroenterology & Hepatology. - : Elsevier BV. - 2468-1253. ; 3:4, s. 252-262
  • Tidskriftsartikel (refereegranskat)abstract
    • Background The population prevalence, clinical characteristics, and associations for Rome IV functional dyspepsia are not known. Following the publication of the Rome IV criteria for functional gastrointestinal disorders, we aimed to assess the prevalence, characteristics, and associations for symptom-based Rome IV functional dyspepsia in adults across the USA, Canada, and the UK. Methods We sent an internet-based cross-sectional health survey to adults in the general population of three English-speaking countries: the USA, Canada, and the UK. We used quota-based sampling to generate demographically balanced and population-representative samples. Individuals were invited to complete an online questionnaire on general health, without mention that the purpose of this survey was to examine gastrointestinal symptoms. We excluded participants who failed two attention-test questions or were excessively inconsistent on the three gastrointestinal questions that were presented twice in the survey for this particular purpose. The survey enquired about demographics, health-care visits, medications, somatisation, quality of life, and symptom-based criteria for Rome IV functional dyspepsia as well as for irritable bowel syndrome (IBS) and functional heartburn. We made subsequent comparisons between participants with Rome IV functional dyspepsia and controls without dyspepsia. The primary objective was to identify participants who fulfilled symptom-based criteria for Rome IV functional dyspepsia and categorise them into postprandial distress syndrome, epigastric pain syndrome, or overlapping subtypes. Findings 6300 general population adults completed the health survey; 2100 each from the USA, Canada, and the UK. 369 responses were deemed inconsistent, leaving data for 5931 adults. Rome IV functional dyspepsia was significantly more prevalent in the USA (232 [12%] of 1949) than in Canada (167 [8%] of 1988) and the UK (152 [8%] of 1994; p< 0 . 0001). The subtype distribution was 61% postprandial distress syndrome, 18% epigastric pain syndrome, and 21% overlapping variant with both syndromes; this pattern was similar across the countries. Participants with functional dyspepsia had significantly greater health impairment and health-care usage than those without dyspepsia. Participants with the overlapping variant showed greater somatisation and poorer quality-of-life scores than did individuals with either postprandial distress syndrome or epigastric pain syndrome alone. In multivariate analysis, independent factors associated with all functional dyspepsia subtypes included worsening quality of life and the presence of symptoms compatible with functional heartburn and IBS, with functional heartburn and IBS having the strongest association with overlapping postprandial distress syndrome and epigastric pain syndrome. Notably, somatisation showed a positive association with postprandial distress syndrome and the overlapping variant, and use of antidepressants showed a negative association with postprandial distress syndrome. Interpretation Approximately 10% of the adult population fulfils symptom-based criteria for Rome IV functional dyspepsia and incurs considerable associated health impairment. The functional dyspepsia subtypes show differing associations, suggesting differences in pathophysiological processes or influences.
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20.
  • Aziz, Imran, et al. (författare)
  • The Prevalence and Impact of Overlapping Rome IV-Diagnosed Functional Gastrointestinal Disorders on Somatization, Quality of Life, and Healthcare Utilization: A Cross-Sectional General Population Study in Three Countries
  • 2018
  • Ingår i: American Journal of Gastroenterology. - : Ovid Technologies (Wolters Kluwer Health). - 0002-9270. ; 113:1, s. 86-96
  • Tidskriftsartikel (refereegranskat)abstract
    • OBJECTIVES: The population prevalence of Rome IV-diagnosed functional gastrointestinal disorders (FGIDs) and their cumulative effect on health impairment is unknown. METHODS: An internet-based cross-sectional health survey was completed by 5,931 of 6,300 general population adults from three English-speaking countries (2100 each from USA, Canada, and UK). Quota-based sampling was used to generate demographically balanced and population representative samples with regards to age, sex, and education level. The survey enquired for demographics, medication, surgical history, somatization, quality of life (QOL), doctor-diagnosed organic GI disease, and criteria for the Rome IV FGIDs. Comparisons were made between those with Rome IV-diagnosed FGIDs against non-GI (healthy) and organic GI disease controls. RESULTS: The number of subjects having symptoms compatible with a FGID was 2,083 (35%) compared with 3,421 (57.7%) non-GI and 427 (7.2%) organic GI disease controls. The most frequently met diagnostic criteria for FGIDs was bowel disorders (n = 1,665, 28.1%), followed by gastroduodenal (n = 627, 10.6%), anorectal (n = 440, 7.4%), esophageal (n = 414, 7%), and gallbladder disorders (n = 10, 0.2%). On average, the 2,083 individuals who met FGID criteria qualified for 1.5 FGID diagnoses, and 742 of them (36%) qualified for FGID diagnoses in more than one anatomic region. The presence of FGIDs in multiple regions was associated with increasing somatization, worse mental/physical QOL, more medical therapies, and a higher prevalence of abdominal surgeries; all P < 0.001. Notably, individuals with FGIDs in multiple regions had greater somatization and worse QOL than organic GI disease controls. CONCLUSIONS: Roughly a third of the general adult population fulfils diagnostic criteria for a Rome IV FGID. In a third of this subset multiple GI regions are involved and this overlap is associated with increased health impairment.
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21.
  • Azofeifa, D. E., et al. (författare)
  • Hydrogen induced changes in the optical properties of Pd capped V thin films
  • 2013
  • Ingår i: Journal of Alloys and Compounds. - : Elsevier BV. - 0925-8388 .- 1873-4669. ; 580:Suppl. 1, s. S114-S118
  • Tidskriftsartikel (refereegranskat)abstract
    • Optical properties of 50 nm thick single crystal vanadium films deposited on double side polished MgO substrates have been obtained from spectrophotometric measurements. The films were coated with a polycrystalline Pd layer (5 nm thick) to protect them from oxidation and to favor absorption of atomic hydrogen. Electrical resistance was recorded while hydrogen pressure was increased slowly up to 750 mbar keeping temperature constant. Simultaneously, under normal incidence of non-polarized radiation [350-950 nm], transmittance spectra of this Pd/V/MgO system were measured. These were numerically inverted to obtain the spectral behavior of the Pd, V. PdHy, and VHx dielectric functions at 22 and 140 degrees C, and at 750 mbar. Hydrogen concentration in V film was first determined from a resisto-optical method. Finally, we demonstrate the possibility to determine the concentration in the Pd and the V layers independently, solely using the changes in the optical transmission. 
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22.
  • Azofeifa, D. E., et al. (författare)
  • Temperature-and hydrogen-induced changes in the optical properties of Pd capped V thin films
  • 2012
  • Ingår i: Physica Scripta. - : IOP Publishing. - 0031-8949 .- 1402-4896. ; 86:6, s. 065702-
  • Tidskriftsartikel (refereegranskat)abstract
    • Optical properties of V thin films deposited on MgO substrates have been obtained from spectrophotometric measurements. The V films were coated with a thin Pd layer to protect them from oxidation and to favor absorption of atomic hydrogen. Electrical resistance was recorded while hydrogen pressure was increased slowly up to 750mbar keeping the temperature constant. Simultaneously, visible and near-infrared transmittance spectra of this Pd/V/MgO system were measured. The spectra were numerically inverted to obtain the spectral behavior of the Pd and V dielectric functions at 22 and 140 degrees C. Hydrogen concentrations were first determined from the combined effect of hydrogen content on the electrical resistance and on the optical direct transmission of the system. Then, determination of these concentrations was improved using retrieved values of the absorption coefficients of the hydrides and taking into account the structural change of V and the volumetric expansion of Pd. Good agreement is established when considering qualitative correlations between spectral features of the optimized PdHy and VHx dielectric functions and band structure calculations and densities of states for these two transition metal hydrides.
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23.
  • Bennet, Sean, et al. (författare)
  • Systemic cytokines are elevated in a subset of patients with irritable bowel syndrome but largely unrelated to symptom characteristics
  • 2018
  • Ingår i: Neurogastroenterology and Motility. - : Wiley. - 1350-1925 .- 1365-2982. ; 30:10
  • Tidskriftsartikel (refereegranskat)abstract
    • BackgroundSerum levels of pro-inflammatory cytokines tend to be increased in irritable bowel syndrome (IBS) patients, or subgroups thereof. Still, the link between cytokine levels and IBS symptoms is unclear. We aim to determine systemic cytokine levels in IBS patients and healthy subjects (HS), confirm the presence of a subset of patients with an increased immune activity and to establish if cytokines are linked to IBS symptoms and pathophysiological factors. MethodsSerum levels of interleukin (IL)-1, IL-6, IL-8, tumor necrosis factor (TNF), and IL-10 were measured. All subjects reported IBS symptoms using validated questionnaires and underwent colonic sensorimotor testing. Multivariate supervised orthogonal partial least squares-discriminant analysis (OPLS-DA) and unsupervised principal component analysis (PCA) and hierarchical cluster analysis (HCA) were implemented. Key ResultsIrritable bowel syndrome patients (n=246) had higher serum levels of IL-1, IL-6, IL-8, TNF, and IL-10 compared to HS (n=21); however, serum cytokine profiles could not discriminate patients from HS. Moreover, cytokine levels were not correlated with symptoms among patients. Supervised OPLS-DA identified 104 patients (40% of patients) and unsupervised HCA analysis identified 49 patients (20%) with an increased immune activity indicated by elevated levels of serum cytokines compared to HS and the other patients. However, irrespective of how patients with increased immune activity were identified they were symptomatically similar to patients with no indication of increased immune activity. Conclusions & InferencesSerum cytokines are elevated in IBS patients compared to HS. Immune activation characterizes a subset of patients, but modest associations between cytokine profile and symptoms suggest immune activity does not directly influence symptoms in IBS.
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24.
  • Broeders, B., et al. (författare)
  • Epidemiology of disorders of gut-brain interaction in Belgium and differences between two language groups: Results from the Rome foundation global epidemiology study
  • 2023
  • Ingår i: Neurogastroenterology and Motility. - 1350-1925. ; 35:6
  • Tidskriftsartikel (refereegranskat)abstract
    • BackgroundThe Rome Foundation carried out a worldwide epidemiology study on DGBI according to the Rome IV criteria in 33 countries, including Belgium. DGBI prevalence varied between continents and countries, but prevalence differences within language groups in a single country have not yet been described. MethodsWe analyzed the prevalence rates of 18 DGBI and their psychosocial impact in Belgium in the French and Dutch language groups. Key ResultsDGBI prevalence was similar in the French-speaking and Dutch-speaking population. Having one or more DGBI was negatively associated with psychosocial well-being. The scores for depression were lower in the Dutch-speaking participants with one or more DGBI compared to the French-speaking participants. Interestingly, we also found significantly lower scores in the general Dutch-speaking versus the French-speaking population for depression and non-gastrointesinal somatic symptoms, and higher global physical health and mental health quality-of-life component scores. In the Dutch-speaking group, medication use for gastric acid was lower, but use of prescribed analgesics was more common. Nevertheless, the use of non-prescribed pain medication was higher in the French-speaking group. Anxiety and sleep medication use was also higher in the latter group. Conclusions & InterferencesThe results of this first in-depth analysis of Rome IV DGBI in Belgium show a higher prevalence for some DGBI in the French-speaking cohort, and a larger associated disease burden. These differences between language/culture groups in the same country support the psychosocial pathophysiological model of DGBI.
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25.
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26.
  • Brunk, Elizabeth, et al. (författare)
  • Recon3D enables a three-dimensional view of gene variation in human metabolism
  • 2018
  • Ingår i: Nature Biotechnology. - : Springer Science and Business Media LLC. - 1087-0156 .- 1546-1696. ; 36:3, s. 272-281
  • Tidskriftsartikel (refereegranskat)abstract
    • Genome-scale network reconstructions have helped uncover the molecular basis of metabolism. Here we present Recon3D, a computational resource that includes three-dimensional (3D) metabolite and protein structure data and enables integrated analyses of metabolic functions in humans. We use Recon3D to functionally characterize mutations associated with disease, and identify metabolic response signatures that are caused by exposure to certain drugs. Recon3D represents the most comprehensive human metabolic network model to date, accounting for 3,288 open reading frames (representing 17% of functionally annotated human genes), 13,543 metabolic reactions involving 4,140 unique metabolites, and 12,890 protein structures. These data provide a unique resource for investigating molecular mechanisms of human metabolism. Recon3D is available at http://vmh.life.
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27.
  • Busby-Whitehead, J., et al. (författare)
  • The aging gut: Symptoms compatible with disorders of gut-brain interaction (DGBI) in older adults in the general population
  • 2024
  • Ingår i: Journal of the American Geriatrics Society. - 0002-8614. ; 72:2, s. 479-489
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Little is known about changes in gastrointestinal symptoms compatible with disorders of gut-brain interaction (DGBI) with increasing age at the population level. The objective of this study was to describe the patterns of DGBI in individuals 65 years of age and above and contrasting them with those of younger adults.Methods: A community sample of 6300 individuals ages 18 and older in the US, UK, and Canada completed an online survey. Quota-based sampling was used to ensure equal proportion of sex and age groups (40% aged 18-39, 40% aged 40-64, 20% aged 65+) across countries, and to control education distributions. The survey included the Rome IV Diagnostic Questionnaire for DGBI, demographic questions, questionnaires measuring overall somatic symptom severity and quality of life, and questions on healthcare utilization, medications, and surgical history.Results: We included 5926 individuals in our analyses; 4700 were 18-64 years of age and 1226 were ages 65+. Symptoms compatible with at least one DGBI were less prevalent in participants ages 65+ vs. ages 18-64 years (34.1% vs. 41.3%, p < 0.0001). For symptoms compatible with upper GI DGBI, lower prevalence for most disorders was noted in the 65+ group. For lower GI DGBI, a different pattern was seen. Prevalence was lower in ages 65+ for irritable bowel syndrome and anorectal pain, but no differences from younger participants for the disorders defined by abnormal bowel habits (constipation and/or diarrhea) were seen. Fecal incontinence was the only DGBI that was more common in ages 65+. Having a DGBI was associated with reduced quality of life, more severe non-GI somatic symptoms, and increased healthcare seeking, both in younger and older participants.Conclusion: Symptoms compatible with DGBI are common, but most of these decrease in older adults at the population level, with the exception of fecal incontinence which increases. This pattern needs to be taken into account when planning GI health care for the growing population of older adults.
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28.
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29.
  • Clevers, Egbert, et al. (författare)
  • Factor Analysis Defines Distinct Upper and Lower Gastrointestinal Symptom Groups Compatible With Rome IV Criteria in a Population-based Study
  • 2018
  • Ingår i: Clinical Gastroenterology and Hepatology. - : Elsevier BV. - 1542-3565. ; 16:8
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND & AIMS: The Rome IV criteria define functional gastrointestinal (GI) disorders by specific combinations of symptoms. It is possible to empirically evaluate these symptom combinations by factor analysis (a statistical procedure that groups variables that correlate). However, this analysis has not been performed for the Rome IV criteria, and factor analyses based on the previous versions of the Rome criteria did not use population-based data. We therefore investigated symptom grouping by the Rome IV questionnaire using factor analysis of a population-based sample. METHODS: The Rome IV questionnaire was completed online in English by 5931 respondents from the United Kingdom, United States, and Canada (49% female, age range, 18-92 years). We performed an exploratory factor analysis on the Rome IV questions. Next, we performed a confirmatory factor analysis to compare the exploratory factor result to that of the Rome IV criteria. RESULTS: The exploratory factor analysis identified 8 factors that accounted for 45% of the variance in response: constipation, diarrhea, irritable bowel syndrome, abdominal pain, heartburn, nausea or vomiting, globus, and other upper GI symptoms. Most factors corresponded to distinct functional GI disorders defined by the Rome IV criteria-exceptions included abdominal pain and upper GI symptoms. In confirmatory factor analysis, the exploratory model fitted slightly better than that based on the Rome IV criteria (root mean square error of approximation, 0.063 vs 0.077). CONCLUSIONS: We used factor analysis to identify distinct upper and lower GI symptom groups that are compatible with the Rome IV criteria. Our findings support the use of the Rome IV criteria in research and clinical practice as a basis for development of diagnostics and management of patients.
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30.
  • Colomier, Esther, 1995, et al. (författare)
  • Global prevalence and burden of meal-related abdominal pain
  • 2022
  • Ingår i: Bmc Medicine. - : Springer Science and Business Media LLC. - 1741-7015. ; 20:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Background Patients with disorders of gut-brain interaction (DGBI) report meal intake to be associated with symptoms. DGBI patients with meal-related symptoms may have more severe symptoms overall and worse health outcomes, but this subgroup has not been well characterized. We aimed to describe the global prevalence of meal-related abdominal pain and characterize this subgroup. Methods The data analyzed originated from the Internet survey component of the population-based Rome Foundation Global Epidemiology Study, completed in 26 countries (n = 54,127). Adult subjects were asked whether they had abdominal pain and how often this was meal-related. Respondents were categorized into "no," "occasional," and "frequent" meal-related abdominal pain groups based on 0%, 10-40%, and >= 50% of the pain episodes being meal-related, respectively. DGBI diagnoses, frequency of other GI symptoms, psychological distress, non-GI somatic symptoms, quality of life, and healthcare utilization were compared between groups. Mixed linear and ordinal regression was used to assess independent associations between psychological distress, non-GI somatic symptoms, quality of life, other GI symptoms, and meal-related abdominal pain. Results Overall, 51.9% of the respondents reported abdominal pain in the last 3 months, and 11.0% belonged to the group with frequent meal-related abdominal pain, which included more females and younger subjects. DGBI diagnoses were more common in subjects with frequent meal-related abdominal pain, and the frequency of several GI symptoms was associated with having more frequent meal-related abdominal pain. Having meal-related abdominal pain more frequently was also associated with more severe psychological distress, non-GI somatic symptoms, and a poorer quality of life. The group with frequent meal-related abdominal pain also more often consulted a doctor for bowel problems compared to the other groups of meal-related abdominal pain. Conclusion Reporting frequent meal-related abdominal pain is common across the globe and associated with other GI and non-GI somatic symptoms, psychological distress, healthcare utilization, and a poorer quality of life. Individuals who frequently experience meal-related abdominal pain also more frequently fulfill the diagnostic criteria for DGBI. Assessing meal-related symptoms in all DGBI patients could be of major importance to improve and individualize symptom management.
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31.
  • Dabkowska, A. P., et al. (författare)
  • Temperature responsive lipid liquid crystal layers with embedded nanogels
  • 2017
  • Ingår i: Chemical Communications. - : Royal Society of Chemistry. - 1359-7345 .- 1364-548X. ; 53:8, s. 1417-1420
  • Tidskriftsartikel (refereegranskat)abstract
    • Polymer nanogels are embedded within layers consisting of a nonlamellar liquid crystalline lipid phase to act as thermoresponsive controllers of layer compactness and hydration. As the nanogels change from the swollen to the collapsed state via a temperature trigger, they enable on-demand release of water from the mixed polymer-lipid layer while the lipid matrix remains intact. Combining stimuli-responsive polymers with responsive lipid-based mesophase systems opens up new routes in biomedical applications such as functional biomaterials, bioanalysis and drug delivery.
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32.
  • Delanaye, Pierre, et al. (författare)
  • CKD : A Call for an Age-Adapted Definition
  • 2019
  • Ingår i: Journal of the American Society of Nephrology. - 1046-6673. ; 30:10, s. 1785-1805
  • Forskningsöversikt (refereegranskat)abstract
    • Current criteria for the diagnosis of CKD in adults include persistent signs of kidney damage, such as increased urine albumin-to-creatinine ratio or a GFR below the threshold of 60 ml/min per 1.73 m2 This threshold has important caveats because it does not separate kidney disease from kidney aging, and therefore does not hold for all ages. In an extensive review of the literature, we found that GFR declines with healthy aging without any overt signs of compensation (such as elevated single-nephron GFR) or kidney damage. Older living kidney donors, who are carefully selected based on good health, have a lower predonation GFR compared with younger donors. Furthermore, the results from the large meta-analyses conducted by the CKD Prognosis Consortium and from numerous other studies indicate that the GFR threshold above which the risk of mortality is increased is not consistent across all ages. Among younger persons, mortality is increased at GFR <75 ml/min per 1.73 m2, whereas in elderly people it is increased at levels <45 ml/min per 1.73 m2 Therefore, we suggest that amending the CKD definition to include age-specific thresholds for GFR. The implications of an updated definition are far reaching. Having fewer healthy elderly individuals diagnosed with CKD could help reduce inappropriate care and its associated adverse effects. Global prevalence estimates for CKD would be substantially reduced. Also, using an age-specific threshold for younger persons might lead to earlier identification of CKD onset for such individuals, at a point when progressive kidney damage may still be preventable.
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33.
  • Eiteneer, D., et al. (författare)
  • Depth-Resolved Composition and Electronic Structure of Buried Layers and Interfaces in a LaNiO3/SrTiO3 Superlatticefroni Soft- and Hard-X-ray Standing-Wave Angle-Resolved Photoemission
  • 2016
  • Ingår i: Journal of Electron Spectroscopy and Related Phenomena. - : Elsevier BV. - 0368-2048 .- 1873-2526. ; 211, s. 70-81
  • Tidskriftsartikel (refereegranskat)abstract
    • LaNiO3 (LNO) is an intriguing member of the rare-earth nickelates in exhibiting a metal-insulator transition for a critical film thickness of about 4 unit cells [Son et al., Appl. Phys. Lett. 96, 062114 (2010)]; however, such thin films also show a transition to a metallic state in superlattices with SrTiO3 (STO) [Son et al., Appl. Phys. Lett. 97, 202109 (2010)]. In order to better understand this transition, we have studied a strained LNO/STO superlattice with 10 repeats of [4 unit-cell LNO/3 unit-cell STO] grown on an (LaAlO3)(0.3)(Sr2AlTaO6)(0.7) substrate using soft x-ray standing-wave-excited angle-resolved photoemission (SWARPES), together with soft- and hard- x-ray photoemission-measurements of core levels and densities-of-states valence spectra. The experimental results are compared with state-of-the-art density functional theory (DFT) calculations of band structures and densities of states. Using core-level rocking curves and x-ray optical modeling to assess the position of the standing wave, SWARPES measurements are carried out for various incidence angles and used to determine interface-specific changes in momentum-resolved electronic structure. We further show that the momentum-resolved behavior of the Ni 3d e(g) and t(2g) states near the Fermi level, as well as those at the bottom of the valence bands, is very similar to recently published SWARPES results for a related La0.7Sr0.3MnO3/SrTiO3 superlattice that was-studied using the same technique (Gray et al., Europhysics Letters 104, 17004 (2013)), which further validates this experimental approach and our conclusions. Our conclusions are also supported in several ways by comparison to DFT calculations for the parent materials and the superlattice, including layer-resolved density-of-states results.
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34.
  • Frändemark, Åsa, 1988, et al. (författare)
  • Work productivity and activity impairment in disorders of gut-brain interaction: Data from the Rome Foundation Global Epidemiology Study
  • 2023
  • Ingår i: United European Gastroenterology Journal. - 2050-6406. ; 11:6, s. 503-513
  • Tidskriftsartikel (refereegranskat)abstract
    • BackgroundDisorders of Gut-Brain Interaction (DGBI) are highly prevalent worldwide, but their effect on work productivity has not gained much attention. Aims and MethodsWe aimed to compare work productivity and activity impairment (WPAI) in persons with and without DGBI in a large population-based cohort and identify factors independently associated with WPAI in subjects with DGBI. Data were collected from Germany, Israel, Italy, Japan, the Netherlands, Poland, Spain and Sweden via Internet surveys as part of the Rome Foundation Global Epidemiology Study. Apart from the Rome IV diagnostic questionnaire, questionnaires evaluating WPAI related to general health (WPAI:GH), psychological distress (PHQ-4), somatic symptom severity (PHQ-15) and other factors were assessed. ResultsOf the 16,820 subjects, 7111 met the criteria for DGBI according to the Rome IV diagnostic questionnaire. Subjects with DGBI were younger (median (interquartile range) age 43 (31-58) vs. 47 (33-62)) and more often female (59.0% vs. 43.7%) compared to subjects without DGBI. Subjects with DGBI had higher absenteeism, presenteeism (poor work productivity due to illness), overall work impairment and activity impairment (p < 0.001) compared with subjects without. For subjects with DGBI affecting more than one anatomical region, WPAI was incrementally higher for each additional region. There were significant differences in WPAI for subjects with DGBI in different countries. Subjects from Sweden had the highest overall work impairment and from Poland the lowest. Using multiple linear regression, male sex, fatigue, psychological distress, somatic symptom severity and number of anatomical regions were independently associated with overall work impairment (p < 0.05 for all). ConclusionIn the general population, people with DGBI have substantial WPAI compared with those without DGBI. The reasons for these findings should be explored further, but having multiple DGBI, psychological distress, fatigue and somatic symptom severity seem to contribute to this impairment associated with DGBI.
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35.
  • Hreinsson, Johann P., 1987, et al. (författare)
  • A comparative study of disorders of gut-brain interaction in Western Europe and Asia based on the Rome foundation global epidemiology study
  • 2023
  • Ingår i: Neurogastroenterology and Motility. - : Wiley. - 1350-1925 .- 1365-2982. ; 35:6
  • Tidskriftsartikel (refereegranskat)abstract
    • ObjectiveMany studies have been published on disorders of the gut-brain interaction (DGBI) in Asia and Western Europe, but no previous study has directly assessed the difference between the two regions. The aim was to compare the prevalence of DGBI in Asia and Western Europe. MethodsWe used data collected in a population-based Internet survey, the Rome Foundation Global Epidemiology Study, from countries in Western Europe (Belgium, France, Germany, Netherlands, Italy, Spain, Sweden, and the United Kingdom) and Asia (China, Japan, South Korea, and Singapore). We assessed DGBI diagnoses (Rome IV Adult Diagnostic Questionnaire), anxiety/depression (Patient Health Questionnaire-4, PHQ-4), non-GI somatic symptoms (PHQ-12), and access to and personal costs of doctor visits. ResultsThe study included 9487 subjects in Asia and 16,314 in Western Europe. Overall, 38.0% had at least one DGBI; younger age, female sex, and higher scores on PHQ4 and PHQ12 were all associated with DGBI. The prevalence of having at least one DGBI was higher in Western Europe than in Asia (39.1% vs 36.1%, OR 1.14 [95% CI 1.08-1.20]). This difference was also observed for DGBI by anatomical regions, most prominently esophageal DGBI (OR 1.67 [1.48-1.88]). After adjustment, the difference in DGBI prevalence diminished and psychological (PHQ-4) and non-GI somatic symptoms (PHQ-12) had the greatest effect on the odds ratio estimates. ConclusionThe prevalence of DGBI is generally higher in Western Europe compared to Asia. A considerable portion of the observed difference in prevalence rates seems to be explained by more severe psychological and non-GI somatic symptoms in Western Europe.
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36.
  • Hruskova, Zdenka, et al. (författare)
  • Characteristics and Outcomes of Patients With Systemic Sclerosis (Scleroderma) Requiring Renal Replacement Therapy in Europe: Results From the ERA-EDTA Registry
  • 2019
  • Ingår i: American Journal of Kidney Diseases. - : W B SAUNDERS CO-ELSEVIER INC. - 0272-6386 .- 1523-6838. ; 73:2, s. 184-193
  • Tidskriftsartikel (refereegranskat)abstract
    • Rationale amp; Objective: Data for outcomes of patients with end-stage renal disease (ESRD) secondary to systemic sclerosis (scleroderma) requiring renal replacement therapy (RRT) are limited. We examined the incidence and prevalence of ESRD due to scleroderma in Europe and the outcomes among these patients following initiation of RRT. Study Design: Registry study of incidence and prevalence and a matched cohort study of clinical outcomes. Setting amp; Participants: Patients represented in any of 19 renal registries that provided data to the European Renal Association-European Dialysis and Transplant Association (ERA-EDTA) Registry between 2002 and 2013. Predictor: Scleroderma as the identified cause of ESRD. Outcomes: Incidence and prevalence of ESRD from scleroderma. Recovery from RRT dependence, patient survival after ESRD, and graft survival after kidney transplantation. Analytical Approach: Incidence and prevalence were calculated using population data from the European Union and standardized to population characteristics in 2005. Patient and graft survival were compared with 2 age- and sex-matched control groups without scleroderma: (1) diabetes mellitus as the cause of ESRD and (2) conditions other than diabetes mellitus as the cause of ESRD. Survival analyses were performed using Kaplan-Meier analysis and Cox regression. Results: 342 patients with scleroderma (0.14% of all incident RRT patients) were included. Between 2002 and 2013, the range of adjusted annual incidence and prevalence rates of RRT for ESRD due to scleroderma were 0.11 to 0.26 and 0.73 to 0.95 per million population, respectively. Recovery of independent kidney function was greatest in the scleroderma group (7.6% vs 0.7% in diabetes mellitus and 2.0% in other primary kidney diseases control group patients, both Pamp;lt;0.001), though time required to achieve recovery was longer. The 5-year survival probability from day 91 of RRT among patients with scleroderma was 38.9% (95% CI, 32.0%-45.8%), whereas 5-year posttransplantation patient survival and 5-year allograft survival were 88.2% (95% CI, 75.3%-94.6%) and 72.4% (95% CI, 55.0%-84.0%), respectively. Adjusted mortality from day 91 on RRT was higher among patients with scleroderma than observed in both control groups (HRs of 1.25 [95% CI, 1.05-1.48] and 2.00 [95% CI, 1.69-2.39]). In contrast, patient and graft survival after kidney transplantation did not differ between patients with scleroderma and control groups. Limitations: No data for extrarenal manifestations, treatment, or recurrence. Conclusions: Survival of patients with scleroderma who receive dialysis for more than 90 days was worse than for those with other causes of ESRD. Patient survival after transplantation was similar to that observed among patients with ESRD due to other conditions. Patients with scleroderma had a higher rate of recovery from RRT dependence than controls.
  •  
37.
  • Huang, I. H., et al. (författare)
  • Worldwide prevalence and burden of gastroparesis-like symptoms as defined by the United European Gastroenterology (UEG) and European Society for Neurogastroenterology and Motility (ESNM) consensus on gastroparesis
  • 2022
  • Ingår i: United European Gastroenterology Journal. - : Wiley. - 2050-6406 .- 2050-6414. ; 10:8, s. 888-897
  • Tidskriftsartikel (refereegranskat)abstract
    • Background/Objectives The global epidemiology of gastroparesis is unknown. The European UEG and European Society for Neurogastroenterology and motility consensus defines Gastroparesis as a condition characterized by delayed gastric emptying in the absence of mechanical obstruction, with a symptom pattern of nausea and/or vomiting and overlapping postprandial distress syndrome (PDS). Real-world evidence of this gastroparesis-like symptom pattern is a crucial step in understanding the epidemiology of gastroparesis. Methods In the Rome Foundation Global Epidemiology Study, 54,127 respondents from 26 countries completed the Rome IV Diagnostic Questionnaire and variables associated with disorders of gut-brain interaction via Internet. We selected subjects with gastroparesis-like symptoms (GPLS) (nausea and/or vomiting >= 1 day/week and simultaneous PDS). Patients reporting organic gastrointestinal disease, or fulfilling criteria for self-induced vomiting, cyclic vomiting or cannabinoid hyperemesis syndrome were excluded. We determined prevalence, associated comorbidities, quality of life (QoL) (PROMIS Global-10), symptoms of anxiety and depression (PHQ-4), somatic symptoms (PHQ-12), and healthcare utilization. Results The global prevalence of GPLS was 0.9% overall and 1.3% among diabetic individuals. Subjects with GPLS showed frequent overlapping of epigastric pain syndrome and irritable bowel syndrome. Subjects with GPLS had significantly lower body mass index, QoL, more non-gastrointestinal somatic complaints, symptoms of anxiety and depression, higher medication usage and doctor visits in the overall and diabetic population, compared to subjects without these symptoms. Conclusions GPLS are common worldwide and more common in diabetic patients. The symptom complex is associated with multiple aspects of illness and an increased healthcare consumption.
  •  
38.
  • Ingason, A. B., et al. (författare)
  • Comparison of the effectiveness and safety of direct oral anticoagulants: a nationwide propensity score-weighted study
  • 2023
  • Ingår i: Blood Advances. - : American Society of Hematology. - 2473-9529 .- 2473-9537. ; 7:11, s. 2564-2572
  • Tidskriftsartikel (refereegranskat)abstract
    • In the pivotal randomized controlled trials (RCTs) for patients with atrial fibrillation, direct oral anticoagulants (DOACs) had similar or even superior efficacy and safety compared with warfarin. However, RCTs comparing different DOACs are nonexistent and previous observational studies have yielded conflicting results. In this nationwide cohort study, rates of any stroke or systemic embolism (stroke/SE) and major bleeding were compared among new users of apixaban, dabigatran, and rivaroxaban with atrial fibrillation from 2014 to 2019. Inverse probability weighting was used to yield balanced study groups, and outcomes were compared using Cox regression. Stroke/SE rates were similar in patients receiving apixaban, dabigatran, and rivaroxaban. Dabigatran was associated with twofold higher rates of myocardial infarction (MI) than rivaroxaban (1.4 events/100 person-years (py) vs 0.7 events/100-py, hazard ratio [HR] 2.21, 95% confidence interval [CI], 1.00-4.90) and apixaban (1.4 events/100-py vs 0.7 events/100-py, HR 2.26, 95% CI, 0.90-5.67), although the second comparison included the possibility of a null effect. Rivaroxaban was associated with higher major bleeding rates compared with apixaban (2.9 events/100-py vs 1.8 events/ 100-py, HR 1.64, 95% CI, 1.13-2.37) and dabigatran (2.9 events/100-py vs 1.4 events/100-py, HR 2.18, 95% CI, 1.21-3.93). Specifically, rivaroxaban had higher rates of major gastrointestinal bleeding and other major bleeding than apixaban. In conclusion, although stroke/SE rates were similar for DOACs, rivaroxaban was associated with higher rates of major bleeding than other DOACs and lower rates of MI than dabigatran. These results may help guide oral anticoagulant selection, especially in patients at high risk of bleeding or MI.
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39.
  • Ingason, A. B., et al. (författare)
  • Rivaroxaban Is Associated With Higher Rates of Gastrointestinal Bleeding Than Other Direct Oral Anticoagulants A Nationwide Propensity Score-Weighted Study
  • 2021
  • Ingår i: ANNALS OF INTERNAL MEDICINE. - : American College of Physicians. - 0003-4819 .- 1539-3704. ; 174:11
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Gastrointestinal bleeding (GIB) rates for direct oral anticoagulants (DOACs) and warfarin have been extensively compared. However, population-based studies comparing GIB rates among different DOACs are limited. Objective: To compare rates of GIB among apixaban, dabigatran, and rivaroxaban. Design: Nationwide population-based cohort study. Setting: Landspitali-The National University Hospital of Iceland and the 4 regional hospitals in Iceland. Patients: New users of apixaban, dabigatran, and rivaroxaban from 2014 to 2019. Measurements: Rates of GIB were compared using inverse probability weighting, Kaplan-Meier survival estimates, and Cox regression. Results: In total, 2157 patients receiving apixaban, 494 patients receiving dabigatran, and 3217 patients receiving rivaroxaban were compared. For all patients, rivaroxaban had higher overall rates of GIB (3.2 vs. 2.5 events per 100 person-years; hazard ratio [HR], 1.42 [95% CI, 1.04 to 1.93]) and major GIB (1.9 vs. 1.4 events per 100 person-years; HR, 1.50 [CI, 1.00 to 2.24]) compared with apixaban. Rivaroxaban also had higher GIB rates than dabigatran, with similar point estimates, although the CIs were wider and included the possibility of a null effect. When only patients with atrial fibrillation were included, rivaroxaban was associated with higher rates of overall GIB than apixaban (HR, 1.40 [CI, 1.01 to 1.94]) or dabigatran (HR, 2.04 [CI, 1.17 to 3.55]). Dabigatran was associated with lower rates of upper GIB than rivaroxaban in both analyses. Limitations: Unmeasured confounding and small subgroup analyses. Conclusion: Rivaroxaban was associated with higher GIB rates than apixaban and dabigatran regardless of treatment indication.
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40.
  • Jonsson, Per R., 1957, et al. (författare)
  • Combining seascape connectivity with cumulative impact assessment in support of ecosystem-based marine spatial planning
  • 2021
  • Ingår i: Journal of Applied Ecology. - : Wiley. - 0021-8901 .- 1365-2664. ; 58:3
  • Tidskriftsartikel (refereegranskat)abstract
    • Cumulative impact assessment (CIA) is a promising approach to guide marine spatial planning (MSP) and management. One limitation of CIA is the neglect of seascape connectivity, which may spread the impact of localized pressures to ambient areas, e.g. through lost dispersal and recruitment of organisms. We here, for the first time, incorporate seascape connectivity into a traditional CIA model using a connectivity matrix, exemplified by dispersal of propagules estimated through biophysical modelling. Two connectivity impacts are identified: the source impact represents downstream areas losing recruits because of reduced larval dispersal from sites affected by the pressure, and the sink impact represents loss of recruits originating from upstream areas prevented from settlement in the site affected by the local pressure. By including seascape connectivity in the Swedish MSP-guiding CIA tool Symphony we demonstrate how to practically account for remote effects of local environmental impact. Our example on blue mussel shows how reducing mussel fitness in a given area may have impacts on mussels far from the acting pressures. Overall, results indicate that connectivity impact for blue mussels plays a minor role in most areas, <10% of the ordinary cumulative impact. However, in some smaller areas, e.g. on offshore banks and the Danish Straits, seascape connectivity may increase ordinary cumulative impact with 20%-30%. In an example of scenario-based CIA analyses of MSP projections, we demonstrate how impacts of particular management actions, e.g. shipping rerouting and wind power developments, can be tracked far from the original area of influence. Depending on the dispersal ability of ecosystem components, a local pressure may impact a considerable area through seascape connectivity, transgressing management units and national borders. Although the mean connectivity impact may be modest for a single ecosystem component, the consideration of seascape connectivity across multiple ecosystem components may significantly alter the mapping of cumulative impact and the assessment of different MSP scenarios. Synthesis and applications. Our extension of Cumulative Impact Assessment offers a new method for mapping and practically integrating seascape connectivity with ecosystem-based MSP and other spatial instruments for policy making, such as marine protected areas.
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41.
  • Josefsson, Axel, 1984, et al. (författare)
  • Global Prevalence and Impact of Rumination Syndrome
  • 2022
  • Ingår i: Gastroenterology. - : Elsevier BV. - 0016-5085. ; 162:3
  • Tidskriftsartikel (refereegranskat)abstract
    • Background & aims: Rumination syndrome is a Disorder of Gut-Brain Interaction (DGBI) of unknown etiology. We aimed to assess its global prevalence and potential associations with other medical conditions. Methods: Data were collected via the Internet in 26 countries. Subjects were evenly distributed by country, sex, and age groups and were invited for a “health survey” using the Rome IV diagnostic questionnaire and a supplementary questionnaire addressing factors potentially associated with DGBI. Results: In all, 54,127 subjects completed the survey (51% male; mean age, 44.3 years). The overall prevalence of rumination syndrome was 3.1% (95% confidence interval [CI], 3.0–3.3%). It was highest in Brazil (5.5% CI, 4.5–6.5) and lowest in Singapore (1.7% CI, 1.1–2.2). The mean age of people with rumination syndrome was 44.5 years (standard deviation, 15.6) and it was more common in females (54.5% vs 45.5%). Factors independently associated with rumination syndrome were depression (odds ratio [OR], 1.46), anxiety (OR, 1.8), body mass index (OR, 1.04), and female sex (OR, 1.19). Subjects with multiple DGBI were at increased risk of having rumination syndrome, with the highest risk in subjects with 4 gastrointestinal regions with DGBI (OR, 15.9 compared with none). Quality of life (QoL) was lower in subjects with rumination syndrome compared with the rest of the cohort (PROMIS-10 score: physical QoL mean 12.9 vs 14.5; mental QoL mean 12.0 vs 13.6). Conclusions: The prevalence of rumination syndrome is higher than reported in most previous population studies and is likely underdiagnosed in clinical practice. Awareness of rumination syndrome should be raised among clinicians to improve care for these patients. © 2022 AGA Institute
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42.
  • Josefsson, Axel, 1984, et al. (författare)
  • Oesophageal symptoms are common and associated with other functional gastrointestinal disorders (FGIDs) in an English-speaking Western population
  • 2018
  • Ingår i: United European Gastroenterology Journal. - : Wiley. - 2050-6406 .- 2050-6414. ; 6:10, s. 1461-1469
  • Tidskriftsartikel (refereegranskat)abstract
    • Background The prevalence and frequency of oesophageal symptoms suggestive of a functional oesophageal disorder according to the Rome IV criteria are unknown. Objective We aimed to describe the prevalence and risk factors for oesophageal symptoms compatible with functional oesophageal disorders in the general population. Methods Data were analysed from a population-based online survey of 6300 individuals aged >= 18 years in the USA, UK and Canada with equal demographic proportions across countries. Questions included the Rome IV diagnostic questionnaire, demographics, medication, somatization, quality of life, and organic gastrointestinal (GI) disease. Multivariate analysis was used to identify factors independently related to oesophageal symptoms. Results Data from 5177 participants (47.8% female; mean age 46.7 years) were available for analysis. Symptom prevalence was 8.1% for globus, 6.5% for heartburn, 4.5% for dysphagia and 5.2% for chest pain, and 17.0% reported at least one oesophageal symptom. Oesophageal symptoms were independently associated with younger age, female gender, previous abdominal surgery and the presence of other functional GI disorders. Reporting oesophageal symptoms was associated with reduced quality of life. Conclusion Oesophageal symptoms are common in the general population and important predictors include other functional GI disorders, age and gender. Oesophageal symptoms are associated with poorer quality of life.
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43.
  • Jung, Christian, et al. (författare)
  • A comparison of very old patients admitted to intensive care unit after acute versus elective surgery or intervention
  • 2019
  • Ingår i: Journal of critical care. - : W B SAUNDERS CO-ELSEVIER INC. - 0883-9441 .- 1557-8615. ; 52, s. 141-148
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: We aimed to evaluate differences in outcome between patients admitted to intensive care unit (ICU) after elective versus acute surgery in a multinational cohort of very old patients (80 years; VIP). Predictors of mortality, with special emphasis on frailty, were assessed.Methods: In total, 5063 VIPs were induded in this analysis, 922 were admitted after elective surgery or intervention, 4141 acutely, with 402 after acute surgery. Differences were calculated using Mann-Whitney-U test and Wilcoxon test. Univariate and multivariable logistic regression were used to assess associations with mortality.Results: Compared patients admitted after acute surgery, patients admitted after elective surgery suffered less often from frailty as defined as CFS (28% vs 46%; p < 0.001), evidenced lower SOFA scores (4 +/- 5 vs 7 +/- 7; p < 0.001). Presence of frailty (CFS >4) was associated with significantly increased mortality both in elective surgery patients (7% vs 12%; p = 0.01), in acute surgery (7% vs 12%; p = 0.02).Conclusions: VIPs admitted to ICU after elective surgery evidenced favorable outcome over patients after acute surgery even after correction for relevant confounders. Frailty might be used to guide clinicians in risk stratification in both patients admitted after elective and acute surgery. 
  •  
44.
  • Kekecs, Zoltan, et al. (författare)
  • Guidelines for the Assessment of Efficacy of Clinical Hypnosis Applications
  • 2022
  • Ingår i: International Journal of Clinical and Experimental Hypnosis. - : Informa UK Limited. - 0020-7144 .- 1744-5183. ; 70:2, s. 104-122
  • Tidskriftsartikel (refereegranskat)abstract
    • Research on the efficacy of hypnosis applications continues to grow, but there remain major gaps between the science and clinical practice. One challenge has been a lack of consensus on which applications of hypnosis are efficacious based on research evidence. In 2018, 6 major hypnosis organizations collaborated to form the Task Force for Establishing Efficacy Standards for Clinical Hypnosis. This paper describes a Guideline for the Assessment of Efficacy of Clinical Hypnosis Applications developed by the Task Force, which makes 10 specific recommendations. The guideline is intended to be a tool for those who want to assess the quality of existing evidence on the efficacy of clinical hypnosis for any particular indication. The paper also discusses methodological issues in the interpretation and implementation of these guidelines. Future papers will report on the other products of the Hypnosis Efficacy Task Force, such as best practice recommendations for outcomes research in hypnosis and an international survey of researchers and clinicians on current practice and attitudes about hypnosis.
  •  
45.
  • Lam, C. Y., et al. (författare)
  • Rome IV Functional Gastrointestinal Disorders and Health Impairment in Subjects With Hypermobility Spectrum Disorders or Hypermobile Ehlers-Danlos Syndrome
  • 2021
  • Ingår i: Clinical Gastroenterology and Hepatology. - : Elsevier BV. - 1542-3565. ; 19:2, s. 277-287
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND & AIMS: Individuals with hypermobility spectrum disorder or hypermobile Ehlers-Danlos Syndrome (HSD/hEDS) are increasingly encountered by gastroenterologists and pose complex clinical challenges. Uncontrolled studies have found functional gastrointestinal disorders (FGIDs) to be common in patients with HSD/hEDS. Some patients have somatic symptoms (medically unexplained symptoms) that might affect FGIDs. We performed a case-control study to determine the prevalence of and factors associated with Rome IV FGIDs in subjects with HSD/hEDS compared with age- and sex-matched population-based controls. METHODS: An online general health survey was completed by 603 individuals with HSD/hEDS in October 2018 (cases) and 603 matched individuals from the population of the United Kingdom (controls) in 2015. The mean participant age was 39 yrs, and 96% were women. The survey included questions about Rome IV FGIDs, non-GI and non-musculoskeletal somatic symptoms (maximum number, 10), quality of life, medical history and healthcare use. The prevalence of FGIDs was compared between cases and controls, with subsequent logistic regression models adjusting for the number of somatic symptoms - used to determine the associations for FGIDs in HSD/hEDS compared with controls. RESULTS: Nearly all subjects (98%) with HSD/hEDS fulfilled symptom-based criteria for 1 or more Rome IV FGIDs, compared with 47% of controls (P < .0001). The gastrointestinal regions most commonly affected by FGIDs in individuals with HSD/hEDS and control subjects were the bowel (90% vs40% of controls), gastroduodenal (70% vs 13% of controls), esophageal (56% vs 6% of controls), and anorectal (53% vs9% of controls); P < .0001. A higher proportion of subjects with HSD/hEDS had FGIDs in 2 or more regions (84% vs 15% of controls; P < .0001). Subjects with HSD/hEDS also reported a significantly higher number of non-GI and non-musculoskeletal somatic symptoms (7.1 vs 3.3 in controls), lower quality of life, and greater healthcare use, including abdominal surgeries and medication use (for example, 84% used analgesics compared with 29% of controls). Almost 40% of subjects with HSD/hEDS reported a diagnosis of chronic fatigue syndrome and/or fibromyalgia. Following adjustments for somatic symptoms, the association for FGIDs in subjects with HSD/hEDS was reduced by as much as 4-fold and in some instances was eliminated. CONCLUSIONS: In a large case-control study of persons with HSD/hEDS, almost all of the cases met criteria for Rome IV FGIDs, incurred considerable health impairment, and had high healthcare use. Patients with HSD/hEDS frequently have somatic symptoms that should be treated to reduce the high burden of gastrointestinal illness in this population.
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46.
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47.
  • Nielsen, Jens B, 1962, et al. (författare)
  • Engineering synergy in biotechnology
  • 2014
  • Ingår i: Nature Chemical Biology. - : Springer Science and Business Media LLC. - 1552-4450 .- 1552-4469. ; 10:5, s. 319-322
  • Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
  •  
48.
  • Oei, Ling, et al. (författare)
  • A genome-wide copy number association study of osteoporotic fractures points to the 6p25.1 locus
  • 2014
  • Ingår i: Journal of Medical Genetics. - : BMJ Publishing Group. - 0022-2593 .- 1468-6244. ; 51:2, s. 122-131
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Osteoporosis is a systemic skeletal disease characterised by reduced bone mineral density and increased susceptibility to fracture; these traits are highly heritable. Both common and rare copy number variants (CNVs) potentially affect the function of genes and may influence disease risk.AIM: To identify CNVs associated with osteoporotic bone fracture risk.METHOD: We performed a genome-wide CNV association study in 5178 individuals from a prospective cohort in the Netherlands, including 809 osteoporotic fracture cases, and performed in silico lookups and de novo genotyping to replicate in several independent studies.RESULTS: A rare (population prevalence 0.14%, 95% CI 0.03% to 0.24%) 210 kb deletion located on chromosome 6p25.1 was associated with the risk of fracture (OR 32.58, 95% CI 3.95 to 1488.89; p=8.69×10(-5)). We performed an in silico meta-analysis in four studies with CNV microarray data and the association with fracture risk was replicated (OR 3.11, 95% CI 1.01 to 8.22; p=0.02). The prevalence of this deletion showed geographic diversity, being absent in additional samples from Australia, Canada, Poland, Iceland, Denmark, and Sweden, but present in the Netherlands (0.34%), Spain (0.33%), USA (0.23%), England (0.15%), Scotland (0.10%), and Ireland (0.06%), with insufficient evidence for association with fracture risk.CONCLUSIONS: These results suggest that deletions in the 6p25.1 locus may predispose to higher risk of fracture in a subset of populations of European origin; larger and geographically restricted studies will be needed to confirm this regional association. This is a first step towards the evaluation of the role of rare CNVs in osteoporosis.
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49.
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50.
  • Palsson, Olafur S., et al. (författare)
  • Current Practices, Experiences, and Views in Clinical Hypnosis : Findings of an International Survey
  • 2023
  • Ingår i: International Journal of Clinical and Experimental Hypnosis. - : Informa UK Limited. - 0020-7144 .- 1744-5183. ; 71:2, s. 92-114
  • Tidskriftsartikel (refereegranskat)abstract
    • An online survey of 691 clinicians who use hypnosis was conducted in 31 countries to gain a broad real-world picture of current practices, views, and experiences in clinical hypnosis. Among 36 common clinical uses, stress reduction, wellbeing and self-esteem-enhancement, surgery preparations, anxiety interventions, mindfulness facilitation, and labor and childbirth applications were the most frequently rated as highly effective (each by ≥70% of raters) in the clinicians’ own experience. Adverse hypnosis-associated effects had been encountered by 55% of clinicians but were generally short-lived and very rarely judged as serious. The most common hypnosis approaches used were Ericksonian (71%), hypnotic relaxation therapy (55%), and traditional hypnosis (50%). Almost all respondents reported regularly using other therapeutic modalities alongside hypnosis. Among a range of client variables potentially affecting therapy, most clinicians rated hypnotist-client rapport (88%) and client motivation (75%) as very or extremely important factors for successful hypnotherapy. The majority of respondents had conducted hypnosis treatment via teletherapy, and 54% of those estimated it to be as effective as in-person treatment.
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