| 1. |
- Wang, Zhaoming, et al.
(författare)
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Imputation and subset-based association analysis across different cancer types identifies multiple independent risk loci in the TERT-CLPTM1L region on chromosome 5p15.33
- 2014
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Ingår i: Human Molecular Genetics. - : Oxford University Press (OUP). - 0964-6906 .- 1460-2083. ; 23:24, s. 6616-6633
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Tidskriftsartikel (refereegranskat)abstract
- Genome-wide association studies (GWAS) have mapped risk alleles for at least 10 distinct cancers to a small region of 63 000 bp on chromosome 5p15.33. This region harbors the TERT and CLPTM1L genes; the former encodes the catalytic subunit of telomerase reverse transcriptase and the latter may play a role in apoptosis. To investigate further the genetic architecture of common susceptibility alleles in this region, we conducted an agnostic subset-based meta-analysis (association analysis based on subsets) across six distinct cancers in 34 248 cases and 45 036 controls. Based on sequential conditional analysis, we identified as many as six independent risk loci marked by common single-nucleotide polymorphisms: five in the TERT gene (Region 1: rs7726159, P = 2.10 × 10(-39); Region 3: rs2853677, P = 3.30 × 10(-36) and PConditional = 2.36 × 10(-8); Region 4: rs2736098, P = 3.87 × 10(-12) and PConditional = 5.19 × 10(-6), Region 5: rs13172201, P = 0.041 and PConditional = 2.04 × 10(-6); and Region 6: rs10069690, P = 7.49 × 10(-15) and PConditional = 5.35 × 10(-7)) and one in the neighboring CLPTM1L gene (Region 2: rs451360; P = 1.90 × 10(-18) and PConditional = 7.06 × 10(-16)). Between three and five cancers mapped to each independent locus with both risk-enhancing and protective effects. Allele-specific effects on DNA methylation were seen for a subset of risk loci, indicating that methylation and subsequent effects on gene expression may contribute to the biology of risk variants on 5p15.33. Our results provide strong support for extensive pleiotropy across this region of 5p15.33, to an extent not previously observed in other cancer susceptibility loci.
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| 2. |
- Sampson, Joshua N., et al.
(författare)
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Analysis of Heritability and Shared Heritability Based on Genome-Wide Association Studies for 13 Cancer Types
- 2015
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Ingår i: Journal of the National Cancer Institute. - : Oxford University Press (OUP). - 0027-8874 .- 1460-2105. ; 107:12
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Tidskriftsartikel (refereegranskat)abstract
- Background: Studies of related individuals have consistently demonstrated notable familial aggregation of cancer. We aim to estimate the heritability and genetic correlation attributable to the additive effects of common single-nucleotide polymorphisms (SNPs) for cancer at 13 anatomical sites. Methods: Between 2007 and 2014, the US National Cancer Institute has generated data from genome-wide association studies (GWAS) for 49 492 cancer case patients and 34 131 control patients. We apply novel mixed model methodology (GCTA) to this GWAS data to estimate the heritability of individual cancers, as well as the proportion of heritability attributable to cigarette smoking in smoking-related cancers, and the genetic correlation between pairs of cancers. Results: GWAS heritability was statistically significant at nearly all sites, with the estimates of array-based heritability, h(l)(2), on the liability threshold (LT) scale ranging from 0.05 to 0.38. Estimating the combined heritability of multiple smoking characteristics, we calculate that at least 24% (95% confidence interval [CI] = 14% to 37%) and 7% (95% CI = 4% to 11%) of the heritability for lung and bladder cancer, respectively, can be attributed to genetic determinants of smoking. Most pairs of cancers studied did not show evidence of strong genetic correlation. We found only four pairs of cancers with marginally statistically significant correlations, specifically kidney and testes (rho = 0.73, SE = 0.28), diffuse large B-cell lymphoma (DLBCL) and pediatric osteosarcoma (rho = 0.53, SE = 0.21), DLBCL and chronic lymphocytic leukemia (CLL) (rho = 0.51, SE = 0.18), and bladder and lung (rho = 0.35, SE = 0.14). Correlation analysis also indicates that the genetic architecture of lung cancer differs between a smoking population of European ancestry and a nonsmoking Asian population, allowing for the possibility that the genetic etiology for the same disease can vary by population and environmental exposures. Conclusion: Our results provide important insights into the genetic architecture of cancers and suggest new avenues for investigation.
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| 3. |
- Jacobs, Kevin B, et al.
(författare)
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Detectable clonal mosaicism and its relationship to aging and cancer.
- 2012
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Ingår i: Nature Genetics. - New York : Nature Publishing Group. - 1061-4036 .- 1546-1718. ; 44:6, s. 651-658
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Tidskriftsartikel (refereegranskat)abstract
- In an analysis of 31,717 cancer cases and 26,136 cancer-free controls from 13 genome-wide association studies, we observed large chromosomal abnormalities in a subset of clones in DNA obtained from blood or buccal samples. We observed mosaic abnormalities, either aneuploidy or copy-neutral loss of heterozygosity, of >2 Mb in size in autosomes of 517 individuals (0.89%), with abnormal cell proportions of between 7% and 95%. In cancer-free individuals, frequency increased with age, from 0.23% under 50 years to 1.91% between 75 and 79 years (P = 4.8 × 10(-8)). Mosaic abnormalities were more frequent in individuals with solid tumors (0.97% versus 0.74% in cancer-free individuals; odds ratio (OR) = 1.25; P = 0.016), with stronger association with cases who had DNA collected before diagnosis or treatment (OR = 1.45; P = 0.0005). Detectable mosaicism was also more common in individuals for whom DNA was collected at least 1 year before diagnosis with leukemia compared to cancer-free individuals (OR = 35.4; P = 3.8 × 10(-11)). These findings underscore the time-dependent nature of somatic events in the etiology of cancer and potentially other late-onset diseases.
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| 6. |
- Algurén, Beatrix, 1977, et al.
(författare)
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Quality indicators and their regular use in clinical practice: results from a survey among users of two cardiovascular National Registries in Sweden
- 2018
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Ingår i: International Journal for Quality in Health Care. - : Oxford University Press (OUP). - 1353-4505 .- 1464-3677. ; 30:10, s. 786-792
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Tidskriftsartikel (refereegranskat)abstract
- Objective To examine the regular use of quality indicators from Swedish cardiovascular National Quality Registries (NQRs) by clinical staff; particularly differences in use between the two NQRs and between nurses and physicians. Design Cross-sectional online survey study. Setting Two Swedish cardiovascular NQRs: (a) Swedish Heart Failure Registry and (b) Swedeheart. Participants Clinicians (n =185; 70% nurses, 26% physicians) via the NQRs’ email networks. Main Outcome Measures Frequency of NQR use for (a) producing healthcare activity statistics; (b) comparing results between similar departments; (c) sharing results with colleagues; (d) identifying areas for quality improvement (QI); (e) surveilling the impact of QI efforts; (f) monitoring effects of implementation of new treatment methods; (g) doing research and (h) educating and informing healthcare professionals and patients. Results Median use of NQRs was 10 times a year (25th and 75th percentiles range: 3–23 times/year). Quality indicators from the NQRs were used mainly for producing healthcare activity statistics. Median use of Swedeheart was six times greater than Swedish Heart Failure Registry (SwedeHF; P < 0.000). Physicians used the NQRs more than twice as often as nurses (18 vs. 7.5 times/year; P < 0.000) and perceived NQR work more often as meaningful. Around twice as many Swedeheart users had the role to participate in data analysis and in QI efforts compared to SwedeHF users. Conclusions Most respondents used quality indicators from the two cardiovascular NQRs infrequently (<3 times/year). The results indicate that linking registration of quality indicators to using them for QI activities increases their routine use and makes them meaningful tools for professionals.
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| 7. |
- Andersson, Ann-Christine, et al.
(författare)
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Challenges to Improve Inter-Professional Care and Service Collaboration for People Living With Psychiatric Disabilities in Ordinary Housing.
- 2016
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Ingår i: Quality Management in Health Care. - : Lippincott Williams and Wilkins Ltd.. - 1063-8628 .- 1550-5154. ; 25:1, s. 44-52
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Tidskriftsartikel (refereegranskat)abstract
- The aim of this study was to describe health care- and social service professionals' experiences of a quality-improvement program implemented in the south of Sweden. The focus of the program was to develop inter-professional collaboration to improve care and service to people with psychiatric disabilities in ordinary housing. Focus group interviews and a thematic analysis were used. The result was captured as themes along steps in process. (I) Entering the quality-improvement program: Lack of information about the program, The challenge of getting started, and Approaching the resources reluctantly. (II) Doing the practice-based improvement work: Facing unprepared workplaces, and Doing twice the work. (III) Looking back-evaluation over 1 year: Balancing theoretical knowledge with practical training, and Considering profound knowledge as an integral part of work. The improvement process in clinical practice was found to be both time and energy consuming, yet worth the effort. The findings also indicate that collaboration across organizational boundaries was broadened, and the care and service delivery were improved.
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| 8. |
- Andersson, Ann-Christine, et al.
(författare)
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Erfarenheter från lärandeseminarier : Barn som anhöriga: Reflektioner från följeforskning
- 2016
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- Under 2015 genomfördes nationella lärandeseminarier för att stärka implementeringen av den lag som ger barn rätt till information, råd och stöd när en förälder plötsligt avlider, är svårt sjuk eller skadad (HSL 2g §). Satsningen var ett förbättringsarbete som omfattade sex landsting som med hjälp av en projektledning träffades vid fyra tillfällen från januari till september. Två av träffarna skedde i Stockholm och två var digitala. Under våren 2015 knöts följeforskning till arbetet med frågeställningar om vilka resultat förbättringsarbetet gav och hur deltagarna upplevde arbetssättet. Syftet var att lyfta fram vad satsningen gav samt att lära inför framtida satsningar – är lärandeseminarier ett användbart arbetssätt för nationella implementeringssatsningar?Rapporten visar att lärandeseminarier tycks vara en användbar form. Teamen kan redovisa att de uppnått många av de mål som de föresatte sig under projekttiden. Det handlade om kartläggning av kunskapsläge och strukturer, kompetensutveckling samt utveckling av rutiner och material. Teamen uppskattade också att få delta i ett nationellt sammanhang som gav inspiration. Samtidigt framkom det önskemål om fortsatt och ännu mer handfast stöd i fortsatt implementering i klinisk verksamhet.
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| 9. |
- Andersson, Ann-Christine, 1968-, et al.
(författare)
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Identification of children as relatives with a systematic approach: a prerequisite in order to offer advice and support
- 2018
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Ingår i: Quality Management in Health Care. - : Wolters Kluwer. - 1063-8628 .- 1550-5154. ; 27:3, s. 172-177
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Tidskriftsartikel (refereegranskat)abstract
- The purpose of this study was to elucidate conditions at all system levels in a specific health care service to develop practices for identification of children as relatives. An interactive research approach with the intention to create mutual learning between practice and research was used. The participating health care service cared for both clinic in- and outpatients with psychiatric disorders. Health care professionals from different system levels (micro, meso, macro) participated, representing different professions. At the first project meeting, it was obvious that there was no systematic approach to identify children as relatives. At the micro level, activities such as a pilot survey and an open house activity were carried out. At the meso level, it was discussed how to better support collaboration between units. At the management (macro) level, it was decided that all units should appoint at least one child agent, with the aim to increase collaboration throughout the whole health care service. To change focus, in this case from only parents to inclusion of children, is an important challenge faced by health care services when forced to incorporate new policies and regulations. The new regulations contribute to increased complexity in already complex organizations. This study highlights that such challenges are underestimated.
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| 10. |
- Andersson, Ann-Christine, 1968-, et al.
(författare)
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Learning through networking in healthcare and welfare : The use of a breakthrough collaborative in the Swedish context
- 2020
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Ingår i: International Journal of Healthcare Management. - : Maney Publishing. - 2047-9700 .- 2047-9719. ; 13:3, s. 236-244
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Tidskriftsartikel (refereegranskat)abstract
- Breakthrough Collaborative (BC) aims at learning through networking, mainly at micro level, and is used as a tool to improve care and welfare organizations. The aim of this study was to explore and illuminate the challenges when applying BC model at meso and macro level. In 2010, the Swedish Health and Medical Services Act stated the responsibility of healthcare professionals to consider children’s needs as relatives. This study uses an interactive collaborative research model. To support healthcare organizations in the implementation of the regulation, county councils/regions in Sweden were invited to take part in a BC during 2015. Six teams from different county councils/regions participated. Team members were interviewed several times during the project time. Data were analyzed with an explorative and descriptive qualitative content analysis. The result illuminates the challenges faced when applying BC at meso and macro level. Most challenges concern preparation, support structures and system connections. There are similarities with the challenges met at micro level when BC is used at meso and macro level. But it seems even more important to consider how the team is constituted at meso and macro level to make use of the learnings and achieve long-term impact in the home organization.
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