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| 2. |
- Docherty, Anna R, et al.
(författare)
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GWAS Meta-Analysis of Suicide Attempt: Identification of 12 Genome-Wide Significant Loci and Implication of Genetic Risks for Specific Health Factors.
- 2023
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Ingår i: The American journal of psychiatry. - : American Psychiatric Association Publishing. - 1535-7228 .- 0002-953X. ; 180:10, s. 723-738
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Tidskriftsartikel (refereegranskat)abstract
- Suicidal behavior is heritable and is a major cause of death worldwide. Two large-scale genome-wide association studies (GWASs) recently discovered and cross-validated genome-wide significant (GWS) loci for suicide attempt (SA). The present study leveraged the genetic cohorts from both studies to conduct the largest GWAS meta-analysis of SA to date. Multi-ancestry and admixture-specific meta-analyses were conducted within groups of significant African, East Asian, and European ancestry admixtures.This study comprised 22 cohorts, including 43,871 SA cases and 915,025 ancestry-matched controls. Analytical methods across multi-ancestry and individual ancestry admixtures included inverse variance-weighted fixed-effects meta-analyses, followed by gene, gene-set, tissue-set, and drug-target enrichment, as well as summary-data-based Mendelian randomization with brain expression quantitative trait loci data, phenome-wide genetic correlation, and genetic causal proportion analyses.Multi-ancestry and European ancestry admixture GWAS meta-analyses identified 12 risk loci at p values <5×10-8. These loci were mostly intergenic and implicated DRD2, SLC6A9, FURIN, NLGN1, SOX5, PDE4B, and CACNG2. The multi-ancestry SNP-based heritability estimate of SA was 5.7% on the liability scale (SE=0.003, p=5.7×10-80). Significant brain tissue gene expression and drug set enrichment were observed. There was shared genetic variation of SA with attention deficit hyperactivity disorder, smoking, and risk tolerance after conditioning SA on both major depressive disorder and posttraumatic stress disorder. Genetic causal proportion analyses implicated shared genetic risk for specific health factors.This multi-ancestry analysis of suicide attempt identified several loci contributing to risk and establishes significant shared genetic covariation with clinical phenotypes. These findings provide insight into genetic factors associated with suicide attempt across ancestry admixture populations, in veteran and civilian populations, and in attempt versus death.
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| 5. |
- Mayes, Maureen D, et al.
(författare)
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Immunochip analysis identifies multiple susceptibility Loci for systemic sclerosis.
- 2014
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Ingår i: American Journal of Human Genetics. - : Elsevier BV. - 0002-9297 .- 1537-6605. ; 94:1, s. 47-61
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Tidskriftsartikel (refereegranskat)abstract
- In this study, 1,833 systemic sclerosis (SSc) cases and 3,466 controls were genotyped with the Immunochip array. Classical alleles, amino acid residues, and SNPs across the human leukocyte antigen (HLA) region were imputed and tested. These analyses resulted in a model composed of six polymorphic amino acid positions and seven SNPs that explained the observed significant associations in the region. In addition, a replication step comprising 4,017 SSc cases and 5,935 controls was carried out for several selected non-HLA variants, reaching a total of 5,850 cases and 9,401 controls of European ancestry. Following this strategy, we identified and validated three SSc risk loci, including DNASE1L3 at 3p14, the SCHIP1-IL12A locus at 3q25, and ATG5 at 6q21, as well as a suggested association of the TREH-DDX6 locus at 11q23. The associations of several previously reported SSc risk loci were validated and further refined, and the observed peak of association in PXK was related to DNASE1L3. Our study has increased the number of known genetic associations with SSc, provided further insight into the pleiotropic effects of shared autoimmune risk factors, and highlighted the power of dense mapping for detecting previously overlooked susceptibility loci.
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| 6. |
- Mullins, Niamh, et al.
(författare)
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Dissecting the Shared Genetic Architecture of Suicide Attempt, Psychiatric Disorders, and Known Risk Factors
- 2022
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Ingår i: Biological Psychiatry. - : Elsevier. - 0006-3223 .- 1873-2402. ; 91:3, s. 313-327
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Suicide is a leading cause of death worldwide, and nonfatal suicide attempts, which occur far more frequently, are a major source of disability and social and economic burden. Both have substantial genetic etiology, which is partially shared and partially distinct from that of related psychiatric disorders.METHODS: We conducted a genome-wide association study (GWAS) of 29,782 suicide attempt (SA) cases and 519,961 controls in the International Suicide Genetics Consortium (ISGC). The GWAS of SA was conditioned on psychiatric disorders using GWAS summary statistics via multitrait-based conditional and joint analysis, to remove genetic effects on SA mediated by psychiatric disorders. We investigated the shared and divergent genetic architectures of SA, psychiatric disorders, and other known risk factors.RESULTS: Two loci reached genome-wide significance for SA: the major histocompatibility complex and an intergenic locus on chromosome 7, the latter of which remained associated with SA after conditioning on psychiatric disorders and replicated in an independent cohort from the Million Veteran Program. This locus has been implicated in risk-taking behavior, smoking, and insomnia. SA showed strong genetic correlation with psychiatric disorders, particularly major depression, and also with smoking, pain, risk-taking behavior, sleep disturbances, lower educational attainment, reproductive traits, lower socioeconomic status, and poorer general health. After conditioning on psychiatric disorders, the genetic correlations between SA and psychiatric disorders decreased, whereas those with nonpsychiatric traits remained largely unchanged.CONCLUSIONS: Our results identify a risk locus that contributes more strongly to SA than other phenotypes and suggest a shared underlying biology between SA and known risk factors that is not mediated by psychiatric disorders.
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| 7. |
- Adamson, Carly, et al.
(författare)
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IGFBP-7 and Outcomes in Heart Failure With Reduced Ejection Fraction : Findings From DAPA-HF.
- 2023
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Ingår i: JACC. Heart failure. - : Elsevier BV. - 2213-1779 .- 2213-1787. ; 11:3, s. 291-304
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Insulin-like growth factor-binding protein-7 (IGFBP-7) has been proposed as a potential prognostic biomarker in heart failure (HF), but the association between elevation in IGFBP-7 and HF outcomes in ambulant patients with heart failure with reduced ejection fraction (HFrEF) is unknown. OBJECTIVES: The authors addressed this question in a post hoc analysis of the DAPA-HF (Dapagliflozin and Prevention of Adverse Outcomes in Heart Failure) trial. METHODS: The primary outcome was a composite of cardiovascular death or a worsening HF event. The risk of adverse outcome was compared across tertiles of IGFBP-7 concentration by means of Cox proportional hazard models adjusted for N-terminal pro-B- type natriuretic peptide (NT-proBNP) and high-sensitivity troponin T (hsTnT). The efficacy of randomized treatment across IGFBP-7 tertiles was assessed. Change in IGFBP-7 at 12 months was compared with the use of geometric means. RESULTS: A total of 3,158 patients had IGFBP-7 measured at baseline, and 2,493 had a repeated measure at 12 months. Patients in the highest tertile of IGFBP-7 had evidence of more advanced HFrEF. The adjusted HR for the primary endpoint in tertile 3, compared with tertile 1, was 1.48 (95% CI: 1.17-1.88). There was no modification of the benefit of dapagliflozin by baseline IGFBP-7 (P interaction = 0.34). Dapagliflozin did not change IGFBP-7 levels over 1 year (P = 0.34). CONCLUSIONS: Higher IGFBP-7 in patients with HFrEF was associated with worse clinical profile and an increased risk of adverse clinical outcomes. IGFBP-7 provided prognostic information incremental to clinical variables, NT-proBNP, and hsTnT. The benefit of dapagliflozin was not modulated by IGFBP-7 level. (Study to Evaluate the Effect of Dapagliflozin on the Incidence of Worsening Heart Failure or Cardiovascular Death in Patients With Chronic Heart Failure [DAPA-HF]; NCT03036124).
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| 11. |
- Docherty, Neil G., et al.
(författare)
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Urinary sodium excretion after gastric bypass surgery
- 2017
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Ingår i: Surgery for Obesity and Related Diseases. - : Elsevier BV. - 1550-7289. ; 13:9, s. 1506-1514
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Tidskriftsartikel (refereegranskat)abstract
- Background: Gut-kidney signaling is implicated in sodium homeostasis and thus blood pressure regulation. Roux-en-Y gastric bypass (RYGB) surgery for morbid obesity confers a pronounced and long-lasting blood pressure lowering effect in addition to significant weight loss. Objectives: We set out to establish whether RYGB is associated with an intrinsic change in urinary sodium excretion that may contribute to the reported blood pressure lowering effects of the procedure. Methods: Five female patients (age range: 28-50 yr) without metabolic or hypertensive co-morbidities were included in a study involving four 24-hour residential visits: once before surgery and 10 days, 3 months, and 20 months after surgery. Creatinine and sodium were measured in fasting plasma samples and 24-hour urine samples and creatinine clearance, estimated glomerular filtration rate, and indices of urinary sodium excretion were calculated. Fasting and 60-minute postprandial blood samples from each study day were assayed for pro-B-type natriuretic peptide (NT-proBNP). Results: Increases in weight-normalized urinary sodium excretion of up to 2.3-fold in magnitude occurred at 20 months after surgery. Median fractional excretion of sodium at 20 months was double that seen before surgery. Fasting NT-proBNP levels were stable or increased (1.5- to 5-fold). Moreover, a small postprandial increase in NT-proBNP was observed after surgery. Conclusions: Renal fractional excretion of sodium is increased after RYGB. A shift toward increased postoperative basal and meal associated levels of NT-proBNP coincides with increased urinary sodium excretion. The data support a working hypothesis that an enhanced natriuretic gut kidney signal after RYGB may be of mechanistic importance in the blood pressure lowering effects of this procedure. (C) 2017 American Society for Metabolic and Bariatric Surgery. All rights reserved.
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| 18. |
- Docherty, Peter, 1938, et al.
(författare)
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Learning mechanisms as means and ends in collaborative managment research
- 2009
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Ingår i: Handbook of collaborative management research. - 1 Oliver's Yard, 55 City Road London EC1Y 1SP : SAGE Publications, Inc.. - 9781412926249 ; , s. 163-182
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Bokkapitel (övrigt vetenskapligt/konstnärligt)abstract
- Learning mechanisms are viewed as a critical component of collaborative management research. In this chapter, the authors review the evolution of a variety of learning mechanisms within four streams of research. Three types of learning mechanisms-cognitive, structural, and procedural-are explored as both ends and means in collaborative management research. Utilizing a five-year research project with Skandia, the nature of the learning mechanisms tapestry, or combination of different types of mechanisms being used at any time, is described, and the role that it played in the collaborative management research is discussed. The last part of the chapter focus on the exploration of three challenges: The multiple roles of learning mechanisms in collaborative management research, the design choices in the formation of learning mechanisms and their potential consequences, and learning mechanisms and the voices of inquiry and practice.
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| 20. |
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| 21. |
- Docherty, Peter, et al.
(författare)
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Strukturella förutsättningar för människans välbefinnande
- 1995. - 1st Edition
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Ingår i: Människan och strukturerna: Organisationsteori för förändring. - Stockholm, Sweden : Nerenius & Santérus. - 9188384659 - 9789188384652 ; , s. 73-105
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Bokkapitel (övrigt vetenskapligt/konstnärligt)
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| 22. |
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| 23. |
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| 24. |
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| 25. |
- Docherty, Peter, 1938, et al.
(författare)
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The changing practice of action research
- 2006
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Ingår i: Jan Löwstedt & Torbjörn Stjernberg (eds.) Producing Management Knowledge. Research as Practice. - : Routledge.
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Bokkapitel (övrigt vetenskapligt/konstnärligt)
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| 30. |
- Hellström, Andreas, 1972, et al.
(författare)
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Management by Dialogue – Developing Integrated Sustainable Healthcare
- 2010
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Ingår i: A time for change - restructuring america's healthcare delivery system.
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Konferensbidrag (refereegranskat)abstract
- Healthcare is growing in complexity and faces change and increased pressure on many fronts. ‘Business as usual’ is no longer feasible. The Skaraborg Hospital Group has been endeavouring since the late 1990s to mobilize and develop its entire staff, at every level and in every area, to full commitment to improving their services by involvement in production, development and management through management by dialogue – making sense of the business together in both representative and direct participation.
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| 31. |
- Huzzard, Tony, et al.
(författare)
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Between Global and Local: Eight European Works Councils in Retrospect and Prospect
- 2005
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Ingår i: Economic and Industrial Democracy. - 0143-831X. ; 26:4, s. 541-568
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Tidskriftsartikel (refereegranskat)abstract
- This article reports on case studies of eight Swedish based European Works Councils (EWCs) with a particular focus on impacts and outcomes. Three issues are explored: a) the benefits of EWCs from both employee and management perspectives; b) whether the EWCs have evolved as genuine forums for information, consultation and negotiation; and c) the effects of EWCs on industrial relations systems – specifically whether their evolution signals a unified, convergent mode of industrial relations engagement at the European level. We conclude that there are little prospects for convergence or transnational bargaining, and that distinct national practices will persist, not only because of opposition from employers but also, and perhaps surprisingly, because of opposition from union quarters in Scandinavia.
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| 32. |
- Jackson, Alice M., et al.
(författare)
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Dapagliflozin and Diuretic Use in Patients With Heart Failure and Reduced Ejection Fraction in DAPA-HF.
- 2020
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Ingår i: Circulation. - 1524-4539. ; 142:11, s. 1040-1054
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: In the DAPA-HF trial (Dapagliflozin and Prevention of Adverse-Outcomes in Heart Failure), the sodium-glucose cotransporter 2 inhibitor dapagliflozin reduced the risk of worsening heart failure and death in patients with heart failure and reduced ejection fraction. We examined the efficacy and tolerability of dapagliflozin in relation to background diuretic treatment and change in diuretic therapy after randomization to dapagliflozin or placebo. METHODS: We examined the effects of study treatment in the following subgroups: no diuretic and diuretic dose equivalent to furosemide $<$40, 40, and $>$40 mg daily at baseline. We examined the primary composite end point of cardiovascular death or a worsening heart failure event and its components, all-cause death and symptoms. RESULTS: Of 4616 analyzable patients, 736 (15.9%) were on no diuretic, 1311 (28.4%) were on $<$40 mg, 1365 (29.6%) were on 40 mg, and 1204 (26.1%) were taking $>$40 mg. Compared with placebo, dapagliflozin reduced the risk of the primary end point across each of these subgroups: hazard ratios were 0.57 (95% CI, 0.36-0.92), 0.83 (95% CI, 0.63-1.10), 0.77 (95% CI, 0.60-0.99), and 0.78 (95% CI, 0.63-0.97), respectively (P for interaction=0.61). The hazard ratio in patients taking any diuretic was 0.78 (95% CI, 0.68-0.90). Improvements in symptoms and treatment toleration were consistent across the diuretic subgroups. Diuretic dose did not change in most patients during follow- up, and mean diuretic dose did not differ between the dapagliflozin and placebo groups after randomization. CONCLUSIONS: The efficacy and safety of dapagliflozin were consistent across the diuretic subgroups examined in DAPA-HF. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03036124.
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| 33. |
- Laarhoven, H, et al.
(författare)
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Orbis medical centre: Designing and constructing sustainable healthcare
- 2009
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Ingår i: In search for sustainable high quality healthcare, Centre for effective organizations/Centre for healthcare improvement international conference, Chalmers University of Technology, Gothenburg, 12-14 October.
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)
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| 34. |
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| 35. |
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| 36. |
- Lifvergren, Svante, 1961, et al.
(författare)
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Online statistical monitoring of critical patient data increases patient safety
- 2008
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Ingår i: 2008 Portland International Center for Management of Engineering and Technology, Technology Management for a Sustainable Economy, PICMET '08; Cape Town; South Africa; 27 July 2008 through 31 July 2008. - 9781890843175 ; , s. 895-899
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Konferensbidrag (refereegranskat)abstract
- In this paper we present an improvement project conducted at a unit responsible for blood thinning treatment at Lidköping hospital in Sweden. The unit coordinates and monitors the treatment of 1200 patients and consists of a heart specialist and five specially trained nurses. Warfarin is an oral anticoagulant (blood thinning) treatment effective for the prevention and treatment of thromboembolic events in various clinical contexts. The project started in the autumn of 2005 as an effort to improve the safety of patients receiving blood thinning therapy. The aim was to reduce morbidity and mortality of patients undergoing warfarin treatment. Since there is a strong association between individual variation in the International Normalized Ratio (INR) and patient morbidity/mortality in warfarin treatment, the focus of the project was to reduce variation in the INR value of patients undergoing warfarin treatment as a way to eventually decrease mortality and morbidity. In this application, an IT-solution was developed in 2006, where process INR-values are monitored online and visualized in a control chart, available to all co workers in the process. The IT-solution proved to be critical in order to encourage continuous improvement in the process The data are updated on a daily basis, stimulating reflection and daily improvement. Analyzing and learning from the data, special causes of variation in INR-values have been identified and removed from the process. The treatment process is now stable, in statistical control and patient safety has increased. As a result, the number of INR values within therapeutic range (values between 2.0-3.0) per week increased from 63% (autumn 2005) to 66% May 2006 to 70% December 2007 (latest data).
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| 37. |
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| 38. |
- Lifvergren, S., et al.
(författare)
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Towards a sustainable healthcare system: Transformation through participation
- 2011
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Ingår i: Organizing for Sustainable Effectiveness. - 2045-0613 .- 2045-0605. ; 1, s. 99-125
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Bokkapitel (övrigt vetenskapligt/konstnärligt)abstract
- This chapter examines the developmental journey toward a sustainable healthcare system in the west of Skaraborg County in Sweden from 2000 to 2010. It tracks a stream of collaborative research projects within the context of the Swedish sustainability debate that were focused on achieving improved care quality, patient safety, efficiency, and efficacy. The case reports how a central government directive to integrate healthcare at the local level – the county – led to the establishment of a development coalition management group that designed and managed the transformation via broad participation and engagement mechanisms. The transformation process toward a more sustainable healthcare system raises theoretical and practical questions about sustainable effectiveness, the role of partizcipation and learning mechanisms such as democratic dialogue conferences in sustainable effectiveness, the tension between planned and emergent change processes, and the challenge of integration in the drive toward a sustainable healthcare system.
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| 39. |
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| 40. |
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| 41. |
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| 42. |
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| 43. |
- Petrie, Mark C, et al.
(författare)
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Effect of Dapagliflozin on Worsening Heart Failure and Cardiovascular Death in Patients With Heart Failure With and Without Diabetes.
- 2020
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Ingår i: JAMA. - : American Medical Association (AMA). - 1538-3598 .- 0098-7484. ; 323:14, s. 1353-1368
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Tidskriftsartikel (refereegranskat)abstract
- Additional treatments are needed for heart failure with reduced ejection fraction (HFrEF). Sodium-glucose cotransporter 2 (SGLT2) inhibitors may be an effective treatment for patients with HFrEF, even those without diabetes.To evaluate the effects of dapagliflozin in patients with HFrEF with and without diabetes.Exploratory analysis of a phase 3 randomized trial conducted at 410 sites in 20 countries. Patients with New York Heart Association classification II to IV with an ejection fraction less than or equal to 40% and elevated plasma N-terminal pro B-type natriuretic peptide were enrolled between February 15, 2017, and August 17, 2018, with final follow-up on June 6, 2019.Addition of once-daily 10 mg of dapagliflozin or placebo to recommended therapy.The primary outcome was the composite of an episode of worsening heart failure or cardiovascular death. This outcome was analyzed by baseline diabetes status and, in patients without diabetes, by glycated hemoglobin level less than 5.7% vs greater than or equal to 5.7%.Among 4744 patients randomized (mean age, 66 years; 1109 [23%] women; 2605 [55%] without diabetes), 4742 completed the trial. Among participants without diabetes, the primary outcome occurred in 171 of 1298 (13.2%) in the dapagliflozin group and 231 of 1307 (17.7%) in the placebo group (hazard ratio, 0.73 [95% CI, 0.60-0.88]). In patients with diabetes, the primary outcome occurred in 215 of 1075 (20.0%) in the dapagliflozin group and 271 of 1064 (25.5%) in the placebo group (hazard ratio, 0.75 [95% CI, 0.63-0.90]) (P value for interaction=.80). Among patients without diabetes and a glycated hemoglobin level less than 5.7%, the primary outcome occurred in 53 of 438 patients (12.1%) in the dapagliflozin group and 71 of 419 (16.9%) in the placebo group (hazard ratio, 0.67 [95% CI, 0.47-0.96]). In patients with a glycated hemoglobin of at least 5.7%, the primary outcome occurred in 118 of 860 patients (13.7%) in the dapagliflozin group and 160 of 888 (18.0%) in the placebo group (hazard ratio, 0.74 [95% CI, 0.59-0.94]) (P value for interaction=.72). Volume depletion was reported as an adverse event in 7.3% of patients in the dapagliflozin group and 6.1% in the placebo group among patients without diabetes and in 7.8% of patients in the dapagliflozin group and 7.8% in the placebo group among patients with diabetes. A kidney adverse event was reported in 4.8% of patients in the dapagliflozin group and 6.0% in the placebo group among patients without diabetes and in 8.5% of patients in the dapagliflozin group and 8.7% in the placebo group among patients with diabetes.In this exploratory analysis of a randomized trial of patients with HFrEF, dapagliflozin compared with placebo, when added to recommended therapy, significantly reduced the risk of worsening heart failure or cardiovascular death independently of diabetes status.ClinicalTrials.gov Identifier: NCT03036124.
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| 46. |
- Tengblad, P, et al.
(författare)
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Understanding a changing world of work
- 2009
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Ingår i: Resource pack for union training on value charestructuring, Leuven:HIVA.
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Bokkapitel (övrigt vetenskapligt/konstnärligt)
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| 47. |
- Werr, Andreas, et al.
(författare)
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Att förändra strukturer – en översikt och jämförelse
- 1995. - 1st Edition
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Ingår i: Människan och strukturerna: Organisationsteori för förändringsarbete. - Stockholm : Nerenius & Santérus. - 9188384659 ; , s. 153-175
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Bokkapitel (övrigt vetenskapligt/konstnärligt)
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| 48. |
- Werr, Andreas, et al.
(författare)
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The functions of methods of change in management consulting
- 1997
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Ingår i: Journal of Organizational Change Management. - : MCB UP Ltd. - 1758-7816 .- 0953-4814. ; 10:4, s. 288-307
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Tidskriftsartikel (refereegranskat)abstract
- States that highly structured methods and tools for bringing about organizational change are frequent features in both the management literature and the practice of management consultants. Reports that, in order to understand the nature and popularity of these methods and tools, a study of the availability and use of methods in business process reengineering BPR projects was carried out in five large consulting companies. Identifies six functions of methods on the basis of this study. Finds that methods play important roles both in the consulting organization and in the consultants interaction with the client in the specific change project. Also reveals that common to the identified functions is an ability to store and transfer knowledge, which contributes to the change process interface for clients and consultants. Shows also that consulting companies with very different professional backgrounds have very similar approaches to BPR projects. Identifies and comments on the similarities between these companies methods in respect of managing change.
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| 49. |
- Niemi, MEK, et al.
(författare)
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- 2021
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swepub:Mat__t
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