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- Gusev, A, et al.
(författare)
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Atlas of prostate cancer heritability in European and African-American men pinpoints tissue-specific regulation
- 2016
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Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 7, s. 10979-
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Tidskriftsartikel (refereegranskat)abstract
- Although genome-wide association studies have identified over 100 risk loci that explain ∼33% of familial risk for prostate cancer (PrCa), their functional effects on risk remain largely unknown. Here we use genotype data from 59,089 men of European and African American ancestries combined with cell-type-specific epigenetic data to build a genomic atlas of single-nucleotide polymorphism (SNP) heritability in PrCa. We find significant differences in heritability between variants in prostate-relevant epigenetic marks defined in normal versus tumour tissue as well as between tissue and cell lines. The majority of SNP heritability lies in regions marked by H3k27 acetylation in prostate adenoc7arcinoma cell line (LNCaP) or by DNaseI hypersensitive sites in cancer cell lines. We find a high degree of similarity between European and African American ancestries suggesting a similar genetic architecture from common variation underlying PrCa risk. Our findings showcase the power of integrating functional annotation with genetic data to understand the genetic basis of PrCa.
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- Wang, Anqi, et al.
(författare)
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Characterizing prostate cancer risk through multi-ancestry genome-wide discovery of 187 novel risk variants
- 2023
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Ingår i: Nature Genetics. - : Springer Nature. - 1061-4036 .- 1546-1718. ; 55:12, s. 2065-2074
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Tidskriftsartikel (refereegranskat)abstract
- The transferability and clinical value of genetic risk scores (GRSs) across populations remain limited due to an imbalance in genetic studies across ancestrally diverse populations. Here we conducted a multi-ancestry genome-wide association study of 156,319 prostate cancer cases and 788,443 controls of European, African, Asian and Hispanic men, reflecting a 57% increase in the number of non-European cases over previous prostate cancer genome-wide association studies. We identified 187 novel risk variants for prostate cancer, increasing the total number of risk variants to 451. An externally replicated multi-ancestry GRS was associated with risk that ranged from 1.8 (per standard deviation) in African ancestry men to 2.2 in European ancestry men. The GRS was associated with a greater risk of aggressive versus non-aggressive disease in men of African ancestry (P = 0.03). Our study presents novel prostate cancer susceptibility loci and a GRS with effective risk stratification across ancestry groups.
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- Conti, David, V, et al.
(författare)
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Trans-ancestry genome-wide association meta-analysis of prostate cancer identifies new susceptibility loci and informs genetic risk prediction
- 2021
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Ingår i: Nature Genetics. - : Springer Nature. - 1061-4036 .- 1546-1718. ; 53:1, s. 65-75
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Tidskriftsartikel (refereegranskat)abstract
- Prostate cancer is a highly heritable disease with large disparities in incidence rates across ancestry populations. We conducted a multiancestry meta-analysis of prostate cancer genome-wide association studies (107,247 cases and 127,006 controls) and identified 86 new genetic risk variants independently associated with prostate cancer risk, bringing the total to 269 known risk variants. The top genetic risk score (GRS) decile was associated with odds ratios that ranged from 5.06 (95% confidence interval (CI), 4.84-5.29) for men of European ancestry to 3.74 (95% CI, 3.36-4.17) for men of African ancestry. Men of African ancestry were estimated to have a mean GRS that was 2.18-times higher (95% CI, 2.14-2.22), and men of East Asian ancestry 0.73-times lower (95% CI, 0.71-0.76), than men of European ancestry. These findings support the role of germline variation contributing to population differences in prostate cancer risk, with the GRS offering an approach for personalized risk prediction. A meta-analysis of genome-wide association studies across different populations highlights new risk loci and provides a genetic risk score that can stratify prostate cancer risk across ancestries.
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- Hansson, Elisabeth K, 1954, et al.
(författare)
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Person-centred care for patients with chronic heart failure - a cost-utility analysis
- 2016
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Ingår i: European Journal of Cardiovascular Nursing. - : Oxford University Press (OUP). - 1474-5151 .- 1873-1953. ; 15:4
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Tidskriftsartikel (refereegranskat)abstract
- Background: Costs of care for patients with chronic heart failure have been estimated at between 1% and 2% of the total health care expenditure in Europe and North America. Two-thirds are for inpatient care. Person-centred care (PCC) asserts that patients are persons and should not be reduced to their diseases alone. Aims: The aim of this study was to estimate the cost–utility of PCC when compared with conventional care in patients hospitalized for worsening chronic heart failure. Methods and results: Data for the cost–utility analysis were collected alongside a prospective clinical intervention study with a controlled before and after design from 2008 to 2010. Patient-specific resources used and preference-based health status data were collected at an individual level. Only 63% received PCC as intended illustrating the difficulties of introducing new methods in established organizations. The group intended to have PCC yielded higher costs in comparison with the conventional care group. The incremental cost was estimated as €98. The costs for those who actually received PCC, per protocol (PP) (63%) were significantly (p=0.026) lower than for those in the conventional care group, with an incremental cost-saving of €863. For the first three months, patients in the conventional care group showed decreasing health-related quality of life, with a corresponding improvement in the PCC(PP) group. Conclusion: It must be emphasized, however, that these positive effects, both cheaper and somewhat better, were obtained only among those receiving the PCC intervention in its intended form, PCC(PP).
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- Winkel, Jörgen, 1946, et al.
(författare)
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Factors facilitating and inhibiting Value Stream Mapping processes at hospital units in three Nordic countries - A Nordic Multicenter study
- 2014
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Ingår i: O. Broberg, N. Fallentin, P. Hasle, P.L. Jensen, A. Kabel, M.E. Larsen, T.Weller (Editors). 11th International Symposium on Human Factors in Organisational Design and Management 46th Annual Nordic Ergonomics Society Conference. - 9788793130135
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- 1.Conceptual framework and Purpose In healthcare Value Stream Mapping (VSM) is a common Lean tool used to improve the efficiency of patient flows by identifying and minimizing waste (Keyte & Locher, 2004). It is a participatory tool, i.e. those affected by this type of rationalization are performing the analyses and subsequently suggesting appropriate interventions. Participation has been shown to be crucial to obtain ownership of the suggested interventions and thereby increase impact. VSM has been shown to be a powerful rationalization tool. However, the resulting interventions may imply physical work intensification and impaired psychosocial work environment. Due to this, Lean is often perceived as a “threat” by employees at hospitals (Härenstam et al 2000, personal communications). Physical and psychosocial working conditions should therefore be taken into account in the rationalization process to obtain sustainable solutions, i.e. solutions that allow for competitive performance and acceptable work environment in a long term perspective. On this background we have complemented the VSM tool by an ergonomic module assisting the users to consider also physical and psychosocial implications of the suggested interventions. This ErgoVSM tool is now evaluated in a Nordic Multicenter Study including Denmark, Iceland and Sweden (Winkel et al, 2012). The aim of this paper is to present observations that may indicate facilitating and inhibiting factors for the VSM process. 2.Methods Seven wards have used the ErgoVSM and seven the traditional VSM. Information was obtained by screening key hospital documents and interviewing participants in the VSM processes. 3.Results In Sweden one out of three wards using VSM decided not to fulfil the VSM process. On Iceland the only ward using VSM also decided not to fulfil their VSM process. The hospitals of the investigated wards using VSM in Sweden and Iceland had a strong primary focus on financial balance of the business according to key documents. Decisions on when and which value stream to analyse were made by management with little/no dialog with the employees. Work environment issues were not discussed as part of this. In addition, Iceland had a short experience of Lean, mainly based on support from McKinsey, an American global management consulting firm that focuses on solving issues of concern to senior management (http://en.wikipedia.org/wiki/McKinsey_%26_Company). Thus, they had no attention to the wellbeing to the employees and their work environment when introducing Lean. In general, the Icelandic Lean coaches had problems motivating the employees. However, they perceived a facilitated VSM process at the investigated ErgoVSM ward. Due to this, the main Lean coach decided to include work environment aspects in the VSM processes performed at other wards not part of the present Multicenter Study. Positive effects on those VSM processes were reported back to the researchers. In Denmark all three wards using VSM fulfilled their VSM process. This hospital had a long Lean experience. The main Lean coach reported process problems during their 3 initial years when using a top-down approach. Before the present project was initiated they had turned to a bottom-up initiation of the VSM processes. The Lean coach also expressed that work environment issues might be articulated as part of the VSM process. All seven wards using ErgoVSM in the 3 countries fulfilled the process. 4.Conclusion When using the Lean tool “Value Stream Mapping” it seems to be important not only to focus on efficiency but also on issues that are perceived important for the well-being of the individual employee. 5.Financial support The Nordic Council of Ministers and national grants. 6.References Härenstam A, Bejerot E, Johansson K, Leijon O, Schéele P. “Mager och god” eller ”Lean and mean”? Samband mellan organisationsförändringar och arbetsförhållanden. In: Barllöf K (Ed.) Smärtgränsen? En antologi om hälsokonsekvenser I magra organisationer. Rådet för arbetslivsforskning, pp 2000 Keyte, B., Locher, D., 2004. The Complete Lean Enterprise. Value Stream Mapping for Administrative and Office Processes. Productivity Press, New York. Winkel J, Birgisdóttir B D, Dudas K, Edwards K, Gunnarsdóttir S, Jarebrant C, Johansson Hanse J (2012). A Nordic work environment complement to Value Stream Mapping (VSM) for sustainable patient flows at hospitals – A NOVO Multicenter study. 6th NOVO Symposium: Sustainable Health Care: Continuous Improvement of Processes and Systems. Karolinska Institute, Stockholm Sweden. November 15-16, 2012, pp 58-59. ISBN: 978-91-637-2380-3
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- Winkel, Jörgen, 1946, et al.
(författare)
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Introduction of Lean/Value Stream Mapping at hospital units in three Nordic countries and expected impact on the working environment - A Nordic Multicenter study
- 2013
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Ingår i: International HELIX Conference 2013.
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Konferensbidrag (refereegranskat)abstract
- Conceptual framework and Purpose A recent review has documented mostly negative effects of rationalization on musculoskeletal and mental health and corresponding risk factors. This goes in particular for the healthcare sector (Westgaard & Winkel, 2011). Lean Practices are increasingly used in healthcare and Value Stream Mapping (VSM) seems to be a commonly used tool to identify and minimize waste (Keyte & Locher, 2004). The health impact of Lean varies considerably between investigations. This may to a large extend be due to differences in the operationalization of Lean (Brännmark et al, 2012). VSM is a participatory tool, i.e. those affected by this type of rationalization are performing the analyses and subsequently suggesting the interventions. Participation has been shown to be crucial to obtain ownership of the suggested interventions and thereby increased impact. On this background rationalizations based on VSM may offer a procedure that also includes working environment issues. In addition, workplaces in the Nordic countries seem to offer good opportunities for realizing a true participatory approach considering also working environment issues when rationalizing a value stream (Guðmundsson, 1993; Westgaard & Winkel, 2011). VSM has been shown to be a powerful rationalization tool in the elimination of non-value-adding tasks (non-VAT). Several studies show that non-VAT generally offer less risky physical and mental exposures (e.g. Kazmierczak et al, 2005; Østensvik et al, 2008; Palmerud et al, 2012; Jonker et al, 2013). According to this, non-VAT is usually named “the porosity of the working day” (Marx, 1867; Westgaard & Winkel, 2011; Winkel & Westgaard, 2001). Strong political demands to maximize efficiency in healthcare may thus potentially result in an excessive rationalization causing a too large reduction in porosity and thus too risky work intensification. In practice Lean is often perceived as a “threat” by employees at hospitals (Härenstam et al, 2000; many personal communications). In contrast, most Lean consultants generally describe Lean as an opportunity for improvements also in terms of the working environment (numerous personal communications). On this background an ergonomic complement to VSM, the ErgoVSM, has been developed based on existing scientific evidence and in close co-operation with Swedish industry and the healthcare sector (Jarebrant et al, 2013). The ErgoVSM also considers health issues, i.e. risk factors for musculoskeletal and mental health in addition to reduction of waste (Jarebrant et al, 2004; 2009). In this paper we present some preliminary data based on 1st line managers’ assessments of expected impact of action plans based on VSM and ErgoVSM. The presented data are retrieved from a larger NOVO Multicenter Study (Winkel et al, 2012). Design/Methodology Fourteen hospital wards in Denmark, Iceland and Sweden are investigated. Seven of these are using VSM and the remaining the ErgoVSM to improve the efficiency of their patient flows. Current and future states are assessed and action plans presented. 1st line managers are then interviewed and asked to assess expected impact of each suggested intervention in the action plan in terms of efficiency, treatment quality, physical and psychosocial working environment. So far five of the fourteen 1st line managers have been interviewed. Two of the wards have used the VSM tool and 3 the ErgoVSM tool. Results and Discussion All together 103 amendments for improved performance have been assessed in the five action plans. Eighty-one of these were assessed also to imply improvements in the working environment. Three suggestions were expected to imply a negative impact and four no impact on the working environment. Fifteen suggestions were not rated as they were decided not to be realized. Using VSM or ErgoVSM did not influence the assessment of expected impact of amendments in the action plan. The dominance of expected positive impact on the working environment of the amendments will be discussed in terms of potential bias and real opportunities. The Multicenter Study includes follow-up investigations of realized impact on the working environment as well as potential national differences between the three investigated countries (cf. Birna & Gunnarsdóttir, 2012; Edwards & Winkel, 2012; Jarebrant et al, 2012).
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