| 1. |
- Blokland, G. A. M., et al.
(författare)
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Sex-Dependent Shared and Nonshared Genetic Architecture Across Mood and Psychotic Disorders
- 2022
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Ingår i: Biological Psychiatry. - : Elsevier BV. - 0006-3223 .- 1873-2402. ; 91:1, s. 102-117
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Tidskriftsartikel (refereegranskat)abstract
- Background: Sex differences in incidence and/or presentation of schizophrenia (SCZ), major depressive disorder (MDD), and bipolar disorder (BIP) are pervasive. Previous evidence for shared genetic risk and sex differences in brain abnormalities across disorders suggest possible shared sex-dependent genetic risk. Methods: We conducted the largest to date genome-wide genotype-by-sex (G×S) interaction of risk for these disorders using 85,735 cases (33,403 SCZ, 19,924 BIP, and 32,408 MDD) and 109,946 controls from the PGC (Psychiatric Genomics Consortium) and iPSYCH. Results: Across disorders, genome-wide significant single nucleotide polymorphism–by-sex interaction was detected for a locus encompassing NKAIN2 (rs117780815, p = 3.2 × 10−8), which interacts with sodium/potassium-transporting ATPase (adenosine triphosphatase) enzymes, implicating neuronal excitability. Three additional loci showed evidence (p < 1 × 10−6) for cross-disorder G×S interaction (rs7302529, p = 1.6 × 10−7; rs73033497, p = 8.8 × 10−7; rs7914279, p = 6.4 × 10−7), implicating various functions. Gene-based analyses identified G×S interaction across disorders (p = 8.97 × 10−7) with transcriptional inhibitor SLTM. Most significant in SCZ was a MOCOS gene locus (rs11665282, p = 1.5 × 10−7), implicating vascular endothelial cells. Secondary analysis of the PGC-SCZ dataset detected an interaction (rs13265509, p = 1.1 × 10−7) in a locus containing IDO2, a kynurenine pathway enzyme with immunoregulatory functions implicated in SCZ, BIP, and MDD. Pathway enrichment analysis detected significant G×S interaction of genes regulating vascular endothelial growth factor receptor signaling in MDD (false discovery rate-corrected p < .05). Conclusions: In the largest genome-wide G×S analysis of mood and psychotic disorders to date, there was substantial genetic overlap between the sexes. However, significant sex-dependent effects were enriched for genes related to neuronal development and immune and vascular functions across and within SCZ, BIP, and MDD at the variant, gene, and pathway levels. © 2021 Society of Biological Psychiatry
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| 2. |
- de Jong, S, et al.
(författare)
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Applying polygenic risk scoring for psychiatric disorders to a large family with bipolar disorder and major depressive disorder
- 2018
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Ingår i: Communications biology. - : Springer Science and Business Media LLC. - 2399-3642. ; 1, s. 163-
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Tidskriftsartikel (refereegranskat)abstract
- Psychiatric disorders are thought to have a complex genetic pathology consisting of interplay of common and rare variation. Traditionally, pedigrees are used to shed light on the latter only, while here we discuss the application of polygenic risk scores to also highlight patterns of common genetic risk. We analyze polygenic risk scores for psychiatric disorders in a large pedigree (n ~ 260) in which 30% of family members suffer from major depressive disorder or bipolar disorder. Studying patterns of assortative mating and anticipation, it appears increased polygenic risk is contributed by affected individuals who married into the family, resulting in an increasing genetic risk over generations. This may explain the observation of anticipation in mood disorders, whereby onset is earlier and the severity increases over the generations of a family. Joint analyses of rare and common variation may be a powerful way to understand the familial genetics of psychiatric disorders.
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| 3. |
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| 4. |
- Zamora, Juan Carlos, et al.
(författare)
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Considerations and consequences of allowing DNA sequence data as types of fungal taxa
- 2018
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Ingår i: IMA Fungus. - : INT MYCOLOGICAL ASSOC. - 2210-6340 .- 2210-6359. ; 9:1, s. 167-185
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Tidskriftsartikel (refereegranskat)abstract
- Nomenclatural type definitions are one of the most important concepts in biological nomenclature. Being physical objects that can be re-studied by other researchers, types permanently link taxonomy (an artificial agreement to classify biological diversity) with nomenclature (an artificial agreement to name biological diversity). Two proposals to amend the International Code of Nomenclature for algae, fungi, and plants (ICN), allowing DNA sequences alone (of any region and extent) to serve as types of taxon names for voucherless fungi (mainly putative taxa from environmental DNA sequences), have been submitted to be voted on at the 11th International Mycological Congress (Puerto Rico, July 2018). We consider various genetic processes affecting the distribution of alleles among taxa and find that alleles may not consistently and uniquely represent the species within which they are contained. Should the proposals be accepted, the meaning of nomenclatural types would change in a fundamental way from physical objects as sources of data to the data themselves. Such changes are conducive to irreproducible science, the potential typification on artefactual data, and massive creation of names with low information content, ultimately causing nomenclatural instability and unnecessary work for future researchers that would stall future explorations of fungal diversity. We conclude that the acceptance of DNA sequences alone as types of names of taxa, under the terms used in the current proposals, is unnecessary and would not solve the problem of naming putative taxa known only from DNA sequences in a scientifically defensible way. As an alternative, we highlight the use of formulas for naming putative taxa (candidate taxa) that do not require any modification of the ICN.
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| 5. |
- Holmer, M., et al.
(författare)
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Nonalcoholic fatty liver disease is an increasing indication for liver transplantation in the Nordic countries
- 2018
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Ingår i: Liver International. - : Wiley. - 1478-3223. ; 38:11, s. 2082-2090
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Tidskriftsartikel (refereegranskat)abstract
- Background & Aims Nonalcoholic fatty liver disease(NAFLD) is the second most common cause of liver transplantation in the US. Data on NAFLD as a liver transplantation indication from countries with lower prevalences of obesity are lacking. We studied the temporal trends of NAFLD as an indication for liver transplantation in the Nordic countries, and compared outcomes for patients with NAFLD to patients with other indications for liver transplantation. MethodResultsPopulation-based cohort study using data from the Nordic Liver Transplant Registry on adults listed for liver transplantation between 1994 and 2015. NAFLD as the underlying indication for liver transplantation was defined as a listing diagnosis of NAFLD/nonalcoholic steatohepatitis, or cryptogenic cirrhosis with a body mass index 25kg/m(2) and absence of other liver diseases. Waiting time for liver transplantation, mortality and withdrawal from the transplant waiting list were registered. Survival after liver transplantation was calculated using multivariable Cox regression, adjusted for age, sex, body mass index and model for end-stage liver disease. A total of 4609 patients listed for liver transplantation were included. NAFLD as the underlying indication for liver transplantation increased from 2.0% in 1994-1995 to 6.2% in 2011-2015 (P=.01) and was the second most rapidly increasing indication. NAFLD patients had higher age, model for end-stage liver disease and body mass index when listed for liver transplantation, but overall survival after liver transplantation was comparable to non--NAFLD patients (aHR 1.03, 95% CI 0.70-1.53 P=.87). ConclusionNAFLD is an increasing indication for liver transplantation in the Nordic countries. Despite more advanced liver disease, NAFLD patients have a comparable survival to other patients listed for liver transplantation.
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| 6. |
- Takala, S., et al.
(författare)
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Practice patterns in diagnostics, staging, and management strategies of gallbladder cancer among Nordic tertiary centers
- 2023
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Ingår i: Scandinavian Journal of Surgery. - : Sage Publications. - 1457-4969 .- 1799-7267. ; 112:3
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Tidskriftsartikel (refereegranskat)abstract
- Background and objective: Gallbladder cancer (GBC) is a rare malignancy in the Nordic countries and no common Nordic treatment guidelines exist. This study aimed to characterize the current diagnostic and treatment strategies in the Nordic countries and disclose differences in these strategies. Methods: This was a survey study with a cross-sectional questionnaire of all 19 university hospitals providing curative-intent surgery for GBC in Sweden, Norway, Denmark, and Finland. Results: In all Nordic countries except Sweden, neoadjuvant/downstaging chemotherapy was used in GBC patients. In T1b and T2, majority of the centers (15-18/19) performed extended cholecystectomy. In T3, majority of the centers (13/19) performed cholecystectomy with resection of segments 4b and 5. In T4, majority of the centers (12-14/19) chose palliative/oncological care. The centers in Sweden extended lymphadenectomy beyond the hepatoduodenal ligament, whereas all other Nordic centers usually limited lymphadenectomy to the hepatoduodenal ligament. All Nordic centers except those in Norway used adjuvant chemotherapy routinely for GBC. There were no major differences between the Nordic centers in diagnostics and follow-up. Conclusions: The surgical and oncological treatment strategies of GBC vary considerably between the Nordic centers and countries.
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| 7. |
- Åberg, F., et al.
(författare)
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Cancer After Liver Transplantation in Children and Young Adults: A Population-Based Study From 4 Nordic Countries
- 2018
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Ingår i: Liver Transplantation. - : Ovid Technologies (Wolters Kluwer Health). - 1527-6465 .- 1527-6473. ; 24:9, s. 1252-1259
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Tidskriftsartikel (refereegranskat)abstract
- Cancer after liver transplantation (LT) constitutes a threat also for young recipients, but cancer risk factors are usually absent in children and large studies on the cancer risk profile in young LT recipients are scarce. Data of patients younger than 30 years who underwent LT during the period 1982‐2013 in the Nordic countries were linked with respective national cancer registries to calculate standardized incidence ratios (SIRs). A total of 37 cancer cases were observed in 923 patients with 7846 person‐years of follow‐up. The SIR for all cancer types, compared with the matched general population, was 9.8 (12.4 for males and 7.8 for females). Cumulative incidence of cancer adjusted for the competing risk of death was 2% at 10 years, 6% at 20 years, and 22% at 25 years after LT. Non‐Hodgkin lymphoma was the most common cancer type (n = 14) followed by colorectal (n = 4) and hepatocellular cancer (n = 4). Age was a significant risk factor for cancer, and the absolute risk of most cancers (except for lymphoma) increased considerably in young adults older than 20 years. The cancer risk pattern is different in pediatric and young LT patients compared with adult recipients. The striking increase in cancer incidence in young adulthood after the second decade of life deserves further consideration in transition programs.
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| 8. |
- Bergsmark, T., et al.
(författare)
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Long-term survival after liver transplantation for alcohol-related liver disease in the Nordic countries
- 2023
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Ingår i: Scandinavian Journal of Gastroenterology. - : Informa UK Limited. - 0036-5521 .- 1502-7708. ; 58:8, s. 923-30
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Tidskriftsartikel (refereegranskat)abstract
- ObjectivesAlcohol-related liver disease (ALD) is among the most common indications for liver transplantation (LTX) in Europe and North America, with good five-year survival rates post-LTX. Here we evaluated survival up to and beyond 20 years after LTX for patients with ALD compared to a comparison group.MethodsPatients with ALD and a comparison group transplanted in the Nordic countries between 1982 and 2020 were included. Data were analyzed using descriptive statistics, Kaplan-Meier curves and predictors of survival were assessed with Cox-regressions.Results831 patients with ALD and 2979 patients in the comparison group were included in the study. Patients with ALD were older at the time of LTX (p < .001) and more likely to be male (p < .001). The estimated median follow-up time was 9.1 years for the ALD-group and 11.1 years for the comparison group. 333 (40.1%) patients with ALD and 1010 (33.9%) patients in the comparison group died during follow-up. The overall survival was impaired for patients with ALD compared to the comparison group (p < .001) and was evident for male and female patients, patients transplanted before and after 2005, and observed in all age-groups except patients over 60 years. Age at transplant, waiting time, year of LTX and country of LTX were associated with decreased survival after LTX for patients with ALD.ConclusionsPatients with ALD have a decreased long-term survival following LTX. This difference was evident in most sub-groups of patients and warrants close follow-up of liver transplanted patients with ALD with focus on risk reduction.
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| 9. |
- Ogink, H., et al.
(författare)
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A strategic tool to improve long-term health outcomes in clinical practice: SHOR driver and association diagram
- 2020
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Ingår i: International Journal for Quality in Health Care. - : Oxford University Press (OUP). - 1353-4505 .- 1464-3677. ; 32:1, s. 20-27
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Tidskriftsartikel (refereegranskat)abstract
- Quality problem or issue: An over-arching principle of healthcare governance in Sweden is to achieve as much health for as many patients as possible given the available resources. With high life expectancy and increased years lived with non-communicable diseases, more effective interventions in prevention and control of non-communicable diseases are needed in order to ensure high-quality healthcare. Initial assessment: Few publications have described a generic and resource-effective method of implementing the perspective of health outcomes in relation to costs in a clinical Swedish university hospital context. To fill this gap, a generic method was developed at Sahlgrenska University hospital in Gothenburg, Sweden. Choice of solution: A System-based driver and association diagram of Health Outcomes in relation to available Resources (SHOR) was developed. The SHOR driver and association diagram comprised different perspectives: health, patient, process, research and cost perspectives. It enabled the translation from long-term health outcomes to applications in clinical practice. Implementation: Three patient groups exemplify the use and implementation of the method of SHOR association and driver diagram; bipolar disorder (psychiatry), primiparous women with spontaneous onset of labour, (obstetric care) and chronic obstructive pulmonary disease (somatic care). Evaluation:The SHOR driver and association diagram enabled a structure to monitor and support quality development towards maximised health outcomes in relation to available resources and associated total costs for a specific patient group. Lessons learned :This method has connected clinical practice, management and research and has been used for both strategic and operational purposes.
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| 10. |
- Algurén, Beatrix, 1977, et al.
(författare)
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In-depth comparison of two quality improvement collaboratives from different healthcare areas based on registry data-possible factors contributing to sustained improvement in outcomes beyond the project time
- 2019
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Ingår i: Implementation Science. - : Springer Science and Business Media LLC. - 1748-5908. ; 14
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundQuality improvement collaboratives (QICs) are widely used to improve healthcare, but there are few studies of long-term sustained improved outcomes, and inconsistent evidence about what factors contribute to success. The aim of the study was to open the black box of QICs and compare characteristics and activities in detail of two differing QICs in relation to their changed outcomes from baseline and the following 3years.MethodsFinal reports of two QICs-one on heart failure care with five teams, and one on osteoarthritis care with seven teams, including detailed descriptions of improvement projects from each QIC's team, were analysed and coded by 18 QIC characteristics and four team characteristics. Goal variables from each team routinely collected within the Swedish Heart Failure Registry (SwedeHF) and the Better Management of Patients with OsteoArthritis Registry (BOA) at year 2013 (baseline), 2014, 2015 and 2016 were analysed with univariate statistics.ResultsThe two QICs differed greatly in design. The SwedeHF-QIC involved eight experts and ran for 12months, whereas the BOA-QIC engaged three experts and ran for 6months. There were about twice as many activities in the SwedeHF-QIC as in the BOA-QIC and they ranged from standardisation of team coordination to better information and structured follow-ups. The outcome results were heterogeneous within teams and across teams and QICs. Both QICs were highly appreciated by the participants and contributed to their learning, e.g. of improvement methods; however, several teams had already reached goal values when the QICs were launched in 2013.ConclusionsEven though many QI activities were carried out, it was difficult to see sustained improvements on outcomes. Outcomes as specific measurable aspects of care in need of improvement should be chosen carefully. Activities focusing on adherence to standard care programmes and on increased follow-up of patients seemed to lead to more long-lasting improvements. Although earlier studies showed that data follow-up and measurement skills as well as well-functioning data warehouses contribute to sustained improvements, the present registries' functionality and QICs at this time did not support those aspects sufficiently. Further studies on QICs and their impact on improvement beyond the project time should investigate the effect of those elements in particular.
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