| 1. |
- Hollestelle, Antoinette, et al.
(författare)
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No clinical utility of KRAS variant rs61764370 for ovarian or breast cancer
- 2016
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Ingår i: Gynecologic Oncology. - : Elsevier BV. - 0090-8258 .- 1095-6859. ; 141:2, s. 386-401
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Tidskriftsartikel (refereegranskat)abstract
- Objective Clinical genetic testing is commercially available for rs61764370, an inherited variant residing in a KRAS 3′ UTR microRNA binding site, based on suggested associations with increased ovarian and breast cancer risk as well as with survival time. However, prior studies, emphasizing particular subgroups, were relatively small. Therefore, we comprehensively evaluated ovarian and breast cancer risks as well as clinical outcome associated with rs61764370. Methods Centralized genotyping and analysis were performed for 140,012 women enrolled in the Ovarian Cancer Association Consortium (15,357 ovarian cancer patients; 30,816 controls), the Breast Cancer Association Consortium (33,530 breast cancer patients; 37,640 controls), and the Consortium of Modifiers of BRCA1 and BRCA2 (14,765 BRCA1 and 7904 BRCA2 mutation carriers). Results We found no association with risk of ovarian cancer (OR = 0.99, 95% CI 0.94-1.04, p = 0.74) or breast cancer (OR = 0.98, 95% CI 0.94-1.01, p = 0.19) and results were consistent among mutation carriers (BRCA1, ovarian cancer HR = 1.09, 95% CI 0.97-1.23, p = 0.14, breast cancer HR = 1.04, 95% CI 0.97-1.12, p = 0.27; BRCA2, ovarian cancer HR = 0.89, 95% CI 0.71-1.13, p = 0.34, breast cancer HR = 1.06, 95% CI 0.94-1.19, p = 0.35). Null results were also obtained for associations with overall survival following ovarian cancer (HR = 0.94, 95% CI 0.83-1.07, p = 0.38), breast cancer (HR = 0.96, 95% CI 0.87-1.06, p = 0.38), and all other previously-reported associations. Conclusions rs61764370 is not associated with risk of ovarian or breast cancer nor with clinical outcome for patients with these cancers. Therefore, genotyping this variant has no clinical utility related to the prediction or management of these cancers.
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| 2. |
- Lawrenson, Kate, et al.
(författare)
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Functional mechanisms underlying pleiotropic risk alleles at the 19p13.1 breast-ovarian cancer susceptibility locus
- 2016
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 7
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Tidskriftsartikel (refereegranskat)abstract
- A locus at 19p13 is associated with breast cancer (BC) and ovarian cancer (OC) risk. Here we analyse 438 SNPs in this region in 46,451 BC and 15,438 OC cases, 15,252 BRCA1 mutation carriers and 73,444 controls and identify 13 candidate causal SNPs associated with serous OC (P=9.2 × 10-20), ER-negative BC (P=1.1 × 10-13), BRCA1-associated BC (P=7.7 × 10-16) and triple negative BC (P-diff=2 × 10-5). Genotype-gene expression associations are identified for candidate target genes ANKLE1 (P=2 × 10-3) and ABHD8 (P<2 × 10-3). Chromosome conformation capture identifies interactions between four candidate SNPs and ABHD8, and luciferase assays indicate six risk alleles increased transactivation of the ADHD8 promoter. Targeted deletion of a region containing risk SNP rs56069439 in a putative enhancer induces ANKLE1 downregulation; and mRNA stability assays indicate functional effects for an ANKLE1 3′-UTR SNP. Altogether, these data suggest that multiple SNPs at 19p13 regulate ABHD8 and perhaps ANKLE1 expression, and indicate common mechanisms underlying breast and ovarian cancer risk.
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| 3. |
- Couch, Fergus J., et al.
(författare)
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Identification of four novel susceptibility loci for oestrogen receptor negative breast cancer
- 2016
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Ingår i: Nature Communications. - : NATURE PUBLISHING GROUP. - 2041-1723. ; 7:11375, s. 1-13
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Tidskriftsartikel (refereegranskat)abstract
- Common variants in 94 loci have been associated with breast cancer including 15 loci with genome-wide significant associations (P<5 x 10(-8)) with oestrogen receptor (ER)-negative breast cancer and BRCA1-associated breast cancer risk. In this study, to identify new ER-negative susceptibility loci, we performed a meta-analysis of 11 genome-wide association studies (GWAS) consisting of 4,939 ER-negative cases and 14,352 controls, combined with 7,333 ER-negative cases and 42,468 controls and 15,252 BRCA1 mutation carriers genotyped on the iCOGS array. We identify four previously unidentified loci including two loci at 13q22 near KLF5, a 2p23.2 locus near WDR43 and a 2q33 locus near PPIL3 that display genome-wide significant associations with ER-negative breast cancer. In addition, 19 known breast cancer risk loci have genome-wide significant associations and 40 had moderate associations (P<0.05) with ER-negative disease. Using functional and eQTL studies we implicate TRMT61B and WDR43 at 2p23.2 and PPIL3 at 2q33 in ER-negative breast cancer aetiology. All ER-negative loci combined account for similar to 11% of familial relative risk for ER-negative disease and may contribute to improved ER-negative and BRCA1 breast cancer risk prediction.
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| 4. |
- Antoniou, Antonis C., et al.
(författare)
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Common alleles at 6q25.1 and 1p11.2 are associated with breast cancer risk for BRCA1 and BRCA2 mutation carriers
- 2011
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Ingår i: Human Molecular Genetics. - : Oxford University Press (OUP). - 0964-6906 .- 1460-2083. ; 20:16, s. 3304-3321
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Tidskriftsartikel (refereegranskat)abstract
- Two single nucleotide polymorphisms (SNPs) at 6q25.1, near the ESR1 gene, have been implicated in the susceptibility to breast cancer for Asian (rs2046210) and European women (rs9397435). A genome-wide association study in Europeans identified two further breast cancer susceptibility variants: rs11249433 at 1p11.2 and rs999737 in RAD51L1 at 14q24.1. Although previously identified breast cancer susceptibility variants have been shown to be associated with breast cancer risk for BRCA1 and BRCA2 mutation carriers, the involvement of these SNPs to breast cancer susceptibility in mutation carriers is currently unknown. To address this, we genotyped these SNPs in BRCA1 and BRCA2 mutation carriers from 42 studies from the Consortium of Investigators of Modifiers of BRCA1/2. In the analysis of 14 123 BRCA1 and 8053 BRCA2 mutation carriers of European ancestry, the 6q25.1 SNPs (r(2) = 0.14) were independently associated with the risk of breast cancer for BRCA1 mutation carriers [ hazard ratio (HR) = 1.17, 95% confidence interval (CI): 1.11-1.23, P-trend = 4.5 x 10(-9) for rs2046210; HR = 1.28, 95% CI: 1.18-1.40, P-trend = 1.3 x 10(-8) for rs9397435], but only rs9397435 was associated with the risk for BRCA2 carriers (HR = 1.14, 95% CI: 1.01-1.28, P-trend = 0.031). SNP rs11249433 (1p11.2) was associated with the risk of breast cancer for BRCA2 mutation carriers (HR = 1.09, 95% CI: 1.02-1.17, P-trend = 0.015), but was not associated with breast cancer risk for BRCA1 mutation carriers (HR = 0.97, 95% CI: 0.92-1.02, P-trend = 0.20). SNP rs999737 (RAD51L1) was not associated with breast cancer risk for either BRCA1 or BRCA2 mutation carriers (P-trend = 0.27 and 0.30, respectively). The identification of SNPs at 6q25.1 associated with breast cancer risk for BRCA1 mutation carriers will lead to a better understanding of the biology of tumour development in these women.
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| 5. |
- Hamdi, Yosr, et al.
(författare)
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Association of breast cancer risk in BRCA1 and BRCA2 mutation carriers with genetic variants showing differential allelic expression : identification of a modifier of breast cancer risk at locus 11q22.3
- 2017
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Ingår i: Breast Cancer Research and Treatment. - : Springer Science and Business Media LLC. - 0167-6806 .- 1573-7217. ; 161:1, s. 117-134
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: Cis-acting regulatory SNPs resulting in differential allelic expression (DAE) may, in part, explain the underlying phenotypic variation associated with many complex diseases. To investigate whether common variants associated with DAE were involved in breast cancer susceptibility among BRCA1 and BRCA2 mutation carriers, a list of 175 genes was developed based of their involvement in cancer-related pathways. Methods: Using data from a genome-wide map of SNPs associated with allelic expression, we assessed the association of ~320 SNPs located in the vicinity of these genes with breast and ovarian cancer risks in 15,252 BRCA1 and 8211 BRCA2 mutation carriers ascertained from 54 studies participating in the Consortium of Investigators of Modifiers of BRCA1/2. Results: We identified a region on 11q22.3 that is significantly associated with breast cancer risk in BRCA1 mutation carriers (most significant SNP rs228595 p = 7 × 10−6). This association was absent in BRCA2 carriers (p = 0.57). The 11q22.3 region notably encompasses genes such as ACAT1, NPAT, and ATM. Expression quantitative trait loci associations were observed in both normal breast and tumors across this region, namely for ACAT1, ATM, and other genes. In silico analysis revealed some overlap between top risk-associated SNPs and relevant biological features in mammary cell data, which suggests potential functional significance. Conclusion: We identified 11q22.3 as a new modifier locus in BRCA1 carriers. Replication in larger studies using estrogen receptor (ER)-negative or triple-negative (i.e., ER-, progesterone receptor-, and HER2-negative) cases could therefore be helpful to confirm the association of this locus with breast cancer risk.
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| 6. |
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| 7. |
- Zeng, Chenjie, et al.
(författare)
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Identification of independent association signals and putative functional variants for breast cancer risk through fine-scale mapping of the 12p11 locus
- 2016
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Ingår i: Breast Cancer Research. - : Springer Science and Business Media LLC. - 1465-5411 .- 1465-542X. ; 18
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Tidskriftsartikel (refereegranskat)abstract
- Background: Multiple recent genome-wide association studies (GWAS) have identified a single nucleotide polymorphism (SNP), rs10771399, at 12p11 that is associated with breast cancer risk. Method: We performed a fine-scale mapping study of a 700 kb region including 441 genotyped and more than 1300 imputed genetic variants in 48,155 cases and 43,612 controls of European descent, 6269 cases and 6624 controls of East Asian descent and 1116 cases and 932 controls of African descent in the Breast Cancer Association Consortium (BCAC; http://bcac.ccge.medschl.cam.ac.uk/), and in 15,252 BRCA1 mutation carriers in the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA). Stepwise regression analyses were performed to identify independent association signals. Data from the Encyclopedia of DNA Elements project (ENCODE) and the Cancer Genome Atlas (TCGA) were used for functional annotation. Results: Analysis of data from European descendants found evidence for four independent association signals at 12p11, represented by rs7297051 (odds ratio (OR) = 1.09, 95 % confidence interval (CI) = 1.06-1.12; P = 3 x 10(-9)), rs805510 (OR = 1.08, 95 % CI = 1.04-1.12, P = 2 x 10(-5)), and rs1871152 (OR = 1.04, 95 % CI = 1.02-1.06; P = 2 x 10(-4)) identified in the general populations, and rs113824616 (P = 7 x 10(-5)) identified in the meta-analysis of BCAC ER-negative cases and BRCA1 mutation carriers. SNPs rs7297051, rs805510 and rs113824616 were also associated with breast cancer risk at P < 0.05 in East Asians, but none of the associations were statistically significant in African descendants. Multiple candidate functional variants are located in putative enhancer sequences. Chromatin interaction data suggested that PTHLH was the likely target gene of these enhancers. Of the six variants with the strongest evidence of potential functionality, rs11049453 was statistically significantly associated with the expression of PTHLH and its nearby gene CCDC91 at P < 0.05. Conclusion: This study identified four independent association signals at 12p11 and revealed potentially functional variants, providing additional insights into the underlying biological mechanism(s) for the association observed between variants at 12p11 and breast cancer risk.
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| 8. |
- Mahajan, Anubha, et al.
(författare)
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Multi-ancestry genetic study of type 2 diabetes highlights the power of diverse populations for discovery and translation
- 2022
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Ingår i: Nature Genetics. - : Springer Nature. - 1061-4036 .- 1546-1718. ; 54:5, s. 560-572
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Tidskriftsartikel (refereegranskat)abstract
- We assembled an ancestrally diverse collection of genome-wide association studies (GWAS) of type 2 diabetes (T2D) in 180,834 affected individuals and 1,159,055 controls (48.9% non-European descent) through the Diabetes Meta-Analysis of Trans-Ethnic association studies (DIAMANTE) Consortium. Multi-ancestry GWAS meta-analysis identified 237 loci attaining stringent genome-wide significance (P < 5 x 10(-9)), which were delineated to 338 distinct association signals. Fine-mapping of these signals was enhanced by the increased sample size and expanded population diversity of the multi-ancestry meta-analysis, which localized 54.4% of T2D associations to a single variant with >50% posterior probability. This improved fine-mapping enabled systematic assessment of candidate causal genes and molecular mechanisms through which T2D associations are mediated, laying the foundations for functional investigations. Multi-ancestry genetic risk scores enhanced transferability of T2D prediction across diverse populations. Our study provides a step toward more effective clinical translation of T2D GWAS to improve global health for all, irrespective of genetic background. Genome-wide association and fine-mapping analyses in ancestrally diverse populations implicate candidate causal genes and mechanisms underlying type 2 diabetes. Trans-ancestry genetic risk scores enhance transferability across populations.
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| 9. |
- Osorio, Ana, et al.
(författare)
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DNA Glycosylases Involved in Base Excision Repair May Be Associated with Cancer Risk in BRCA1 and BRCA2 Mutation Carriers.
- 2014
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Ingår i: PLoS Genetics. - : Public Library of Science (PLoS). - 1553-7404. ; 10:4
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Tidskriftsartikel (refereegranskat)abstract
- Single Nucleotide Polymorphisms (SNPs) in genes involved in the DNA Base Excision Repair (BER) pathway could be associated with cancer risk in carriers of mutations in the high-penetrance susceptibility genes BRCA1 and BRCA2, given the relation of synthetic lethality that exists between one of the components of the BER pathway, PARP1 (poly ADP ribose polymerase), and both BRCA1 and BRCA2. In the present study, we have performed a comprehensive analysis of 18 genes involved in BER using a tagging SNP approach in a large series of BRCA1 and BRCA2 mutation carriers. 144 SNPs were analyzed in a two stage study involving 23,463 carriers from the CIMBA consortium (the Consortium of Investigators of Modifiers of BRCA1 and BRCA2). Eleven SNPs showed evidence of association with breast and/or ovarian cancer at p<0.05 in the combined analysis. Four of the five genes for which strongest evidence of association was observed were DNA glycosylases. The strongest evidence was for rs1466785 in the NEIL2 (endonuclease VIII-like 2) gene (HR: 1.09, 95% CI (1.03-1.16), p = 2.7×10-3) for association with breast cancer risk in BRCA2 mutation carriers, and rs2304277 in the OGG1 (8-guanine DNA glycosylase) gene, with ovarian cancer risk in BRCA1 mutation carriers (HR: 1.12 95%CI: 1.03-1.21, p = 4.8×10-3). DNA glycosylases involved in the first steps of the BER pathway may be associated with cancer risk in BRCA1/2 mutation carriers and should be more comprehensively studied.
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| 10. |
- Vigorito, Elena, et al.
(författare)
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Fine-Scale Mapping at 9p22.2 Identifies Candidate Causal Variants That Modify Ovarian Cancer Risk in BRCA1 and BRCA2 Mutation Carriers
- 2016
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Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 11:7
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Tidskriftsartikel (refereegranskat)abstract
- Population-based genome wide association studies have identified a locus at 9p22.2 associated with ovarian cancer risk, which also modifies ovarian cancer risk in BRCA1 and BRCA2 mutation carriers. We conducted fine-scale mapping at 9p22.2 to identify potential causal variants in BRCA1 and BRCA2 mutation carriers. Genotype data were available for 15,252 (2,462 ovarian cancer cases) BRCA1 and 8,211 (631 ovarian cancer cases) BRCA2 mutation carriers. Following genotype imputation, ovarian cancer associations were assessed for 4,873 and 5,020 SNPs in BRCA1 and BRCA2 mutation carriers respectively, within a retrospective cohort analytical framework. In BRCA1 mutation carriers one set of eight correlated candidate causal variants for ovarian cancer risk modification was identified (top SNP rs10124837, HR: 0.73, 95% CI: 0.68 to 0.79, p-value 2x 10-16). These variants were located up to 20 kb upstream of BNC2. In BRCA2 mutation carriers one region, up to 45 kb upstream of BNC2, and containing 100 correlated SNPs was identified as candidate causal (top SNP rs62543585, HR: 0.69, 95% CI: 0.59 to 0.80, p-value 1.0 x 10-6). The candidate causal in BRCA1 mutation carriers did not include the strongest associated variant at this locus in the general population. In sum, we identified a set of candidate causal variants in a region that encompasses the BNC2 transcription start site. The ovarian cancer association at 9p22.2 may be mediated by different variants in BRCA1 mutation carriers and in the general population. Thus, potentially different mechanisms may underlie ovarian cancer risk for mutation carriers and the general population.
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| 11. |
- Beal, Jacob, et al.
(författare)
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Robust estimation of bacterial cell count from optical density
- 2020
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Ingår i: Communications Biology. - : Springer Science and Business Media LLC. - 2399-3642. ; 3:1
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Tidskriftsartikel (refereegranskat)abstract
- Optical density (OD) is widely used to estimate the density of cells in liquid culture, but cannot be compared between instruments without a standardized calibration protocol and is challenging to relate to actual cell count. We address this with an interlaboratory study comparing three simple, low-cost, and highly accessible OD calibration protocols across 244 laboratories, applied to eight strains of constitutive GFP-expressing E. coli. Based on our results, we recommend calibrating OD to estimated cell count using serial dilution of silica microspheres, which produces highly precise calibration (95.5% of residuals <1.2-fold), is easily assessed for quality control, also assesses instrument effective linear range, and can be combined with fluorescence calibration to obtain units of Molecules of Equivalent Fluorescein (MEFL) per cell, allowing direct comparison and data fusion with flow cytometry measurements: in our study, fluorescence per cell measurements showed only a 1.07-fold mean difference between plate reader and flow cytometry data.
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| 12. |
- Ding, Yuan C, et al.
(författare)
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A nonsynonymous polymorphism in IRS1 modifies risk of developing breast and ovarian cancers in BRCA1 and ovarian cancer in BRCA2 mutation carriers
- 2012
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Ingår i: Cancer Epidemiology, Biomarkers and Prevention. - : American Association for Cancer Research. - 1055-9965 .- 1538-7755. ; 21:8, s. 1362-1370
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: We previously reported significant associations between genetic variants in insulin receptor substrate 1 (IRS1) and breast cancer risk in women carrying BRCA1 mutations. The objectives of this study were to investigate whether the IRS1 variants modified ovarian cancer risk and were associated with breast cancer risk in a larger cohort of BRCA1 and BRCA2 mutation carriers.METHODS: IRS1 rs1801123, rs1330645, and rs1801278 were genotyped in samples from 36 centers in the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA). Data were analyzed by a retrospective cohort approach modeling the associations with breast and ovarian cancer risks simultaneously. Analyses were stratified by BRCA1 and BRCA2 status and mutation class in BRCA1 carriers.RESULTS: Rs1801278 (Gly972Arg) was associated with ovarian cancer risk for both BRCA1 (HR, 1.43; 95% confidence interval (CI), 1.06-1.92; P = 0.019) and BRCA2 mutation carriers (HR, 2.21; 95% CI, 1.39-3.52, P = 0.0008). For BRCA1 mutation carriers, the breast cancer risk was higher in carriers with class II mutations than class I mutations (class II HR, 1.86; 95% CI, 1.28-2.70; class I HR, 0.86; 95%CI, 0.69-1.09; P(difference), 0.0006). Rs13306465 was associated with ovarian cancer risk in BRCA1 class II mutation carriers (HR, 2.42; P = 0.03).CONCLUSION: The IRS1 Gly972Arg single-nucleotide polymorphism, which affects insulin-like growth factor and insulin signaling, modifies ovarian cancer risk in BRCA1 and BRCA2 mutation carriers and breast cancer risk in BRCA1 class II mutation carriers.Impact: These findings may prove useful for risk prediction for breast and ovarian cancers in BRCA1 and BRCA2 mutation carriers.
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| 13. |
- Blanton, Michael R., et al.
(författare)
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Sloan Digital Sky Survey IV : Mapping the Milky Way, Nearby Galaxies, and the Distant Universe
- 2017
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Ingår i: Astronomical Journal. - : IOP Publishing Ltd. - 0004-6256 .- 1538-3881. ; 154:1
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Tidskriftsartikel (refereegranskat)abstract
- We describe the Sloan Digital Sky Survey IV (SDSS-IV), a project encompassing three major spectroscopic programs. The Apache Point Observatory Galactic Evolution Experiment 2 (APOGEE-2) is observing hundreds of thousands of Milky Way stars at high resolution and. high signal-to-noise ratios in the near-infrared. The Mapping Nearby Galaxies at Apache Point Observatory (MaNGA) survey is obtaining spatially resolved spectroscopy for thousands of nearby galaxies (median z similar to 0.03). The extended Baryon Oscillation Spectroscopic Survey (eBOSS) is mapping the galaxy, quasar, and neutral gas distributions between z similar to 0.6 and 3.5 to constrain cosmology using baryon acoustic oscillations, redshift space distortions, and the shape of the power spectrum. Within eBOSS, we are conducting two major subprograms: the SPectroscopic IDentification of eROSITA Sources (SPIDERS), investigating X-ray AGNs. and galaxies in X-ray clusters, and the Time Domain Spectroscopic Survey (TDSS), obtaining spectra of variable sources. All programs use the 2.5 m Sloan Foundation Telescope at the. Apache Point Observatory; observations there began in Summer 2014. APOGEE-2 also operates a second near-infrared spectrograph at the 2.5 m du Pont Telescope at Las Campanas Observatory, with observations beginning in early 2017. Observations at both facilities are scheduled to continue through 2020. In keeping with previous SDSS policy, SDSS-IV provides regularly scheduled public data releases; the first one, Data Release 13, was made available in 2016 July.
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| 14. |
- Bolton, Kelly L., et al.
(författare)
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Association Between BRCA1 and BRCA2 Mutations and Survival in Women With Invasive Epithelial Ovarian Cancer
- 2012
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Ingår i: JAMA: The Journal of the American Medical Association. - : American Medical Association (AMA). - 1538-3598. ; 307:4, s. 382-390
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Tidskriftsartikel (refereegranskat)abstract
- Context Approximately 10% of women with invasive epithelial ovarian cancer (EOC) carry deleterious germline mutations in BRCA1 or BRCA2. A recent article suggested that BRCA2-related EOC was associated with an improved prognosis, but the effect of BRCA1 remains unclear. Objective To characterize the survival of BRCA carriers with EOC compared with noncarriers and to determine whether BRCA1 and BRCA2 carriers show similar survival patterns. Design, Setting, and Participants A pooled analysis of 26 observational studies on the survival of women with ovarian cancer, which included data from 1213 EOC cases with pathogenic germline mutations in BRCA1 (n=909) or BRCA2 (n=304) and from 2666 noncarriers recruited and followed up at variable times between 1987 and 2010 (the median year of diagnosis was 1998). Main Outcome Measure Five-year overall mortality. Results The 5-year overall survival was 36% (95% CI, 34%-38%) for noncarriers, 44% (95% CI, 40%-48%) for BRCA1 carriers, and 52% (95% CI, 46%-58%) for BRCA2 carriers. After adjusting for study and year of diagnosis, BRCA1 and BRCA2 mutation carriers showed a more favorable survival than noncarriers (for BRCA1: hazard ratio [HR], 0.78; 95% CI, 0.68-0.89; P<.001; and for BRCA2: HR, 0.61; 95% CI, 0.50-0.76; P<.001). These survival differences remained after additional adjustment for stage, grade, histology, and age at diagnosis (for BRCA1: HR, 0.73; 95% CI, 0.64-0.84; P<.001; and for BRCA2: HR, 0.49; 95% CI, 0.39-0.61; P<.001). The BRCA1 HR estimate was significantly different from the HR estimated in the adjusted model (P for heterogeneity=.003). Conclusion Among patients with invasive EOC, having a germline mutation in BRCA1 or BRCA2 was associated with improved 5-year overall survival. BRCA2 carriers had the best prognosis. JAMA. 2012;307(4):382-390
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| 15. |
- B Jensen, Irene, et al.
(författare)
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Promoting Evidence-Based Practice for Improved Occupational Safety and Health at Workplaces in Sweden. Report on a Practice-Based Research Network Approach.
- 2020
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Ingår i: International Journal of Environmental Research and Public Health. - : MDPI. - 1661-7827 .- 1660-4601. ; 17:15
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Tidskriftsartikel (refereegranskat)abstract
- Despite the rapid growth in research and R&D expenditures, the translation of research into practice is limited. One approach to increase the translation and utilization of research is practice based research networks. With the aim of strengthening evidence-based practice (EBP) within occupational health services in Sweden (OH-Services), a practice-based research network (PBRN-OSH) was developed. The PBRN-OSH includes researchers and representatives from end-users. This paper reports on the development, outputs and lessons learned in the PBRN-OSH. The PBRN-OSH resulted in several practice-based research projects as well as different measures to ensure EBP in OSH such as the governmentally sanctioned national guidelines for the OH-services. Moreover, results show that the competence in EBP increased among practitioners at the OH-services. Conducting research in a PBRN is more resource demanding; however, this does not imply that it is less cost effective. To succeed in increasing the utility of research findings via PBRN, resources must be invested into an infrastructure that supports collaboration in the PBRN, including costs for a variety of means of dissemination. Further, translation activities need to be included in academic career paths and reward systems if a major improvement in the impact and return of investments from research is to be expected.
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| 16. |
- Bergström, Gunnar, et al.
(författare)
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A comprehensive workplace intervention and its outcome with regard to lifestyle, health and sick leave : the AHA study
- 2008
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Ingår i: Work. - 1051-9815 .- 1875-9270. ; 31:2, s. 167-180
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Tidskriftsartikel (refereegranskat)abstract
- This study is a prospective multicentre cohort study entitled Work and Health in the Processing and Engineering Industries, the AHA Study (AHA is the Swedish abbreviation for the study). Four large workplaces in Sweden participated during the years from 2000 to 2003. The present report has two objectives: (1) to present a comprehensive occupational health intervention programme and (2) to evaluate this programme with a focus on lifestyle (smoking and exercise), health related quality of life (HRQoL) and sick leave. Interventions were provided on an individual and group level, including evidence-based methods for four health/focus areas (individual level) and a group intervention based on a survey-feedback methodology. The analyses in this report were exclusively employed at an organizational level. The proportion of smokers decreased at three companies and the course of the HRQoL was advantageous at two of the companies as compared to a gainfully employed reference group. A significant decrease in sick leave was revealed at one company, whereas a break in an ascending sick-leave trend appeared at a second company as compared to their respective corporate groups. This comprehensive workplace intervention programme appears to have had positive effects on smoking habits, HRQoL and sick leave.
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| 17. |
- Bergström, Gunnar, Professor, et al.
(författare)
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A psychometric evaluation of the Swedish version of the Multidimensional Pain Inventory (MPI‐S): a gender differentiated evaluation
- 1999
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Ingår i: European Journal of Pain. - : Wiley. - 1090-3801 .- 1532-2149. ; 3:3, s. 261-273
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Tidskriftsartikel (refereegranskat)abstract
- A need to consider possible gender differences in pain research has been recognized by researchers during the last decades. As part of a psychometric evaluation of the Swedish version of the Multidimensional Pain Inventory (MPI-S), we performed gender-differentiated analyses of the internal consistency, validity and sensitivity to change of the MPI-S in a sample of 235 individuals (129 females, 106 males) suffering from long-term non-specific pain from the lower back and/or neck region. The construct validation and sensitivity analyses were performed by using validated self-report measures and direct observational assessment techniques as external constructs. For sections 1 and 2 of the MPI-S, the results support the internal consistency (alpha coefficients ranged from 0.74 to 0.85 for females and 0.62 to 0.89 for males) and construct validity across gender. The General Activity (GA) scale of section 3 of the MPI-S displayed acceptable internal consistency across gender (alpha = 0.79 for females, 0.80 for males) but not a satisfactory construct validity. Furthermore, the results yielded some support for the sensitivity to change of the Pain Severity (PS), Interference (1), Life Control (LC) and Affective Distress (AD) scales (from section 1) across gender. Unfortunately, the GA scale did not display a satisfactory sensitivity either for females or males. Altogether, the results showed a similar pattern across gender, although some divergences were detected, such as the substantially weaker negative correlation between perceived supportive behaviour from significant others and punishing responses for males compared to females. In conclusion, we recommend the use of sections 1 and 2 of the MPI-S as a psychometrically evaluated and comprehensive instrument in the assessment of individuals suffering from chronic non-specific low back pain or neck pain.
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| 18. |
- Bergström, Gunnar, Professor, et al.
(författare)
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Long-term, non-specific spinal pain: reliable and valid subgroups of patients
- 2001
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Ingår i: Behaviour Research and Therapy. - : Elsevier. - 0005-7967 .- 1873-622X. ; 39:1, s. 75-87
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Tidskriftsartikel (refereegranskat)abstract
- The aim of this study was to identify reliable and valid subgroups of spinal pain patients, using data from the Swedish version of the Multidimensional Pain Inventory (MPI-S). A second aim was to test the generalisability of the three patient profiles described in earlier studies on the MPI (”adaptive coper”, ”dysfunctional” and ”interpersonally distressed” patients). The study base consisted of two samples of individuals suffering from long-term, non-specific spinal pain and the results were validated across these samples. Cluster analysis was used to detect distinct groups of patients and the validity of these subgroups was evaluated on variables not used to generate the cluster solution. One subgroup was characterised by lower pain severity, lower interference with everyday activities, lower affective distress and higher life control than the other two subgroups. This patient profile was similar to the MPI adaptive coper patients. A second subgroup resembled the dysfunctional patient profile, thus displaying a worse adjustment to chronic pain than the AC patients. The third patient group reported significantly lower levels of social support from “significant others” than the other subgroups. This patient profile was similar to that of the interpersonally distressed patient group. Taken together, the results support the reliability, validity and generalisability of three subgroups of chronic pain patients derived from the MPI-S.
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| 19. |
- Bergström, Gunnar, Professor, et al.
(författare)
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Psychosocial and Behavioural Assessment of Chronic Pain: Recommendations for Clinicians and Researchers
- 1998
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Ingår i: Scandinavian Journal of Behaviour Therapy. - : Taylor & Francis. - 0284-5717. ; 27:3, s. 114-123
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Tidskriftsartikel (refereegranskat)abstract
- A variety of methods have been developed for the assessment of chronic benign pain. In research or in clinical practise, choosing an adequate measurement technique can be a laborious task. This article has two main purposes: to report on some basic features to consider when selecting assessment instruments, and to present a review of some psychosocial and behavioural measurement methods for the assessment of chronic benign pain. The selected methods have, with one exception, been evaluated on Swedish chronic pain populations and are used in international pain research. In conclusion, we recommend the use of psychometrically sound instruments, and that the purposes for use of a measure have to be thoroughly considered in advance. We also emphasize that in clinical practise, each separate measure must be interpreted in a wider context, where clinical findings and judgements are considered as a whole. In addition, none of the single reviewed assessment techniques can replace the communication between the patient and the clinician.
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| 20. |
- Bergström, Gunnar, Professor, et al.
(författare)
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The impact of psychologically different patient groups on outcome after a vocational rehabilitation program for long-term spinal pain patients
- 2001
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Ingår i: Pain. - : LWW. - 0304-3959 .- 1872-6623. ; 93:3, s. 229-237
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Tidskriftsartikel (refereegranskat)abstract
- A better knowledge of differential treatment outcomes for subgroups of chronic spinal pain patients may, for instance, help clinicians in treatment planning or pain researchers in treatment outcome research. The purpose of this prospective study was to evaluate the predictive validity of a subgroup classification based on the Swedish version of the (West Haven Yale) Multidimensional Pain Inventory, the MPI-S. Patients referred to a vocational rehabilitation program were classified into one of three groups, labeled ‘adaptive copers’, ‘dysfunctional’ patients, and ‘interpersonally distressed’ patients, and followed over an 18-month follow-up period. The outcome variables were absence from work (defined as sick listing plus early retirement), general health status, and utilization of health care resources. To our knowledge, the predictive validity of the MPI subgroups has not been evaluated regarding sick listing and early retirement after rehabilitation. As hypothesized, the results showed that the ‘dysfunctional’ patient group had significantly more registered absences from work and reported higher utilization of health care, over the follow-up period compared to the ‘adaptive copers’. Furthermore, as hypothesized, the ‘interpersonally distressed’ and ‘dysfunctional’ patient groups report a poorer general health status than the ‘adaptive copers’ over the whole follow-up period. However, contrary to our hypothesis, the proportion of improved patients did not differ significantly between the subgroups. Altogether, the predictive validity of the MPI-S subgroup classification was mainly confirmed. The clinical implications of this study suggest that the matching of treatment to patient needs may enhance treatment outcome, reduce pain and suffering among chronic spinal pain patients and facilitate a better health economic allocation of treatment resources.
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| 21. |
- Busch, Hillevi, et al.
(författare)
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Patterns of sickness absence a decade after pain-related multidisciplinary rehabilitation
- 2011
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Ingår i: Pain. - : Elsevier. - 0304-3959 .- 1872-6623. ; 152:8, s. 1727-1733
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Tidskriftsartikel (refereegranskat)abstract
- Multidisciplinary programmes using a vocational approach can enhance work return in chronic pain patients, but little is known about the long-term effects of rehabilitation. The current study examined the patterns of sickness absence 10 years after participation in 3 treatment groups (physiotherapy, cognitive behavioural therapy, and vocational multidisciplinary rehabilitation) in comparison to a control group receiving treatment-as-usual. Cost-effectiveness was also assessed. Two hundred fourteen patients participated in a randomized controlled trial and were followed-up via register data 10 years after the interventions. On average, persons in multidisciplinary rehabilitation had 42.98 fewer days on sickness absence per year compared to those treated-as-usual (95% confidence interval −82.45 to −3.52, P=0.03). The corresponding reduction of sickness absence after physiotherapy and cognitive behavioural therapy was not significantly different from the control group. The effect of rehabilitation seems to be more pronounced for disability pension than for sick leave. The economic analyses showed substantial cost savings for individuals in the multidisciplinary group compared to the control group.
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| 22. |
- Horneij, Eva, et al.
(författare)
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Sick leave among home-care personnel: a longitudinal study of risk factors
- 2004
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Ingår i: BMC Musculoskeletal Disorders. - : Springer Science and Business Media LLC. - 1471-2474. ; 5:1, s. 38-38
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Tidskriftsartikel (refereegranskat)abstract
- Background Sick leave due to neck, shoulder and back disorders (NSBD) is higher among health-care workers, especially nursing aides/assistant nurses, compared with employees in other occupations. More information is needed about predictors of sick leave among health care workers. The aim of the study was to assess whether self-reported factors related to health, work and leisure time could predict: 1) future certified sick leave due to any cause, in nursing aides/assistant nurses (Study group I) and 2) future self-reported sick leave due to NSBD in nursing aides/assistant nurses (Study group II). Methods Study group I, comprised 443 female nursing aides/assistant nurses, not on sick leave at baseline when a questionnaire was completed. Data on certified sick leave were collected after 18 months. Study group II comprised 274 of the women, who at baseline reported no sick leave during the preceding year due to NSBD and who participated at the 18 month follow-up. Data on sick leave due to NSBD were collected from the questionnaire at 18 months. The associations between future sick leave and factors related to health, work and leisure time were tested by logistic regression analyses. Results Health-related factors such as previous low back disorders (OR: 1.89; 95% CI 1.20–2.97) and previous sick leave (OR 6.40; 95%CI 3.97–10.31), were associated with a higher risk of future sick leave due to any cause. Factors related to health, work and leisure time, i.e. previous low back disorders (OR: 4.45; 95% CI 1.27–15.77) previous sick leave, not due to NSBD (OR 3.30; 95%CI 1.33–8.17), high strain work (OR 2.34; 95%CI 1.05–5.23) and high perceived physical exertion in domestic work (OR 2.56; 95%CI 1.12–5.86) were associated with a higher risk of future sick leave due to NSBD. In the final analyses, previous low back disorders and previous sick leave remained significant in both study groups. Conclusion The results suggest a focus on previous low back disorders and previous sick leave for the design of early prevention programmes aiming at reducing future sick leave due to any cause, as well as due to NSBD, among nursing aides/assistant nurses. A multifactorial approach may be of importance in the early prevention of sick leave due to NSBD.
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| 23. |
- Jensen, Irene B., et al.
(författare)
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A gender-differentiated evaluation of the Swedish version of the rheumatology attitudes index (RAI)
- 1997
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Ingår i: Scandinavian Journal of Behaviour Therapy. - : Informa UK Limited. - 0284-5717. ; 26:1, s. 36-45
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Tidskriftsartikel (refereegranskat)abstract
- The aim of this study was to carry out a gender-differentiated evaluation of the Swedish version of the Rheumatology Attitudes Index (RAI). A translation of the RAI into Swedish was performed. This translated version was applied to a study sample consisting of 37 men and 84 women suffering from non-specific neck and back pain. The RAI was administered three times during a six months period. Reliability was tested by calculating alpha coefficients and test-retest correlations. Construct validity was investigated with variables based on the theoretical concept from which the RAI was developed. Important differences between men and women were found. Internal consistency proved to be higher in the female sample, while the validity was more congruent in the male sample. Overall, the results are ambiguous, thus indicating that the RAI requires further investigation using a gender-differentiated approach before being applied in clinical and research practice. This study demonstrates that in order to obtain meaningful, quantitative and evaluated measures, gender differentiation needs to be included in the development and use of assessment instruments.
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| 24. |
- Jensen, Irene B., et al.
(författare)
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A randomized controlled component analysis of a behavioral medicine rehabilitation program for chronic spinal pain: are the effects dependent on gender?
- 2001
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Ingår i: Pain. - : LWW. - 0304-3959 .- 1872-6623. ; 91:1, s. 65-78
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Tidskriftsartikel (refereegranskat)abstract
- The aim of the present study was to evaluate the outcome of a behavioral medicine (BM) rehabilitation program and the outcome of its two main components, compared to a ‘treatment-as-usual’ control group (CG). The study employed a 4×4 repeated-measures design with four groups and four assessment periods (pre-treatment, post-treatment, 6-month follow-up, and 18-month follow-up). The group studied consisted of subjects on sick leave identified in a nationwide health insurance scheme in Sweden. After inclusion, the subjects were randomized to one of four conditions, which were: (1) behavior-oriented physical therapy (PT); (2) cognitive behavioral therapy (CBT); (3) BM rehabilitation consisting of PT+CBT (BM); (4) a ‘treatment-as-usual’ CG. The treatments were given over a period of 4 weeks, PT and CBT on a part-time basis and BM on a full-time basis. Outcome variables were sick leave, early retirement, and health-related quality of life (measured using the Short Form Health Survey, SF-36). The results showed that the risk of being granted full-time early retirement was significantly lower for females in PT and CBT compared to the CG during the 18-month follow-up period. However, the total absence from work (sick listing plus early retirement) in days over the 18-month follow-up period was not significantly different in the CG compared to the treatments. On the SF-36, women in CBT and BM reported a significantly better health-related quality of life than women in the CG at the 18-month follow-up. No significant differences for men were found on the SF-36 scales. In conclusion, the results revealed gender differences in the outcome of the treatments and that the components of this BM program yielded as good results as the whole program.
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| 25. |
- Jensen, Irene B., et al.
(författare)
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Assessing the Needs of Patients in Pain: A Matter of Opinion?
- 2000
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Ingår i: Spine. - : LWW. - 0362-2436 .- 1528-1159. ; 25:21, s. 2816-2823
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Tidskriftsartikel (refereegranskat)abstract
- Study Design. A prospective cohort study including patients with nonspecific spinal pain was performed.Objectives. To investigate whether the use of expert judgment in routine practice can provide a basis for reliable decision making concerning the need for intervention in patients with spinal pain and their ability to benefit from treatment.Summary of Background Data. A wide range of instruments and techniques are used to assess and treat patients with spinal pain. Many instruments are used without being clinimetrically tested.Methods. A questionnaire concerning the patients’ need of treatment and their potential to assimilate it was sent to experts in the health care arena: physicians, physical therapists, social insurance officers. The experts included were those connected with patients participating in a larger outcome study. Two cohorts of patients (sample 1, n = 217; sample 2, n = 257) were followed for 6 and 12 months, during which time the patients’ health and work status were mapped.Results. No acceptable agreement was found between any of the experts’ ratings of patients’ needs and potential for rehabilitation. Logistic regression showed that the experts’ judgments were based almost solely on the age of the patient. The prediction analyses showed that the most consistent predictor of the patients’ status at the 6-month follow-up assessment was the patients’ own belief in the existence of effective treatments and their perceived ability for learning to cope with the condition.Conclusions. Expert judgment as exercised in routine practice cannot be used as basis for reliable decision making concerning the need of the patient with spinal pain for intervention and the patient’s ability to benefit from treatment.
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| 26. |
- Kastrati, Gránit, et al.
(författare)
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Genetic Influence on Nociceptive Processing in the Human Brain : A Twin Study
- 2022
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Ingår i: Cerebral Cortex. - : Oxford University Press. - 1047-3211 .- 1460-2199. ; 32:2, s. 266-274
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Tidskriftsartikel (refereegranskat)abstract
- Nociceptive processing in the human brain is complex and involves several brain structures and varies across individuals. Determining the structures that contribute to interindividual differences in nociceptive processing is likely to improve our understanding of why some individuals feel more pain than others. Here, we found specific parts of the cerebral response to nociception that are under genetic influence by employing a classic twin-design. We found genetic influences on nociceptive processing in the midcingulate cortex and bilateral posterior insula. In addition to brain activations, we found genetic contributions to large-scale functional connectivity (FC) during nociceptive processing. We conclude that additive genetics influence specific brain regions involved in nociceptive processing. The genetic influence on FC during nociceptive processing is not limited to core nociceptive brain regions, such as the dorsal posterior insula and somatosensory areas, but also involves cognitive and affective brain circuitry. These findings improve our understanding of human pain perception and increases chances to find new treatments for clinical pain.
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| 27. |
- Linton, Steven J., 1952-, et al.
(författare)
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The secondary prevention of low back pain : a controlled study with follow-up
- 1989
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Ingår i: Pain. - : Elsevier. - 0304-3959 .- 1872-6623. ; 36:2, s. 197-207
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Tidskriftsartikel (refereegranskat)abstract
- The current investigation studied the effectiveness of a secondary prevention program for nurses with back pain who were deemed at risk for developing a chronic problem. A 2 × 3 repeated measures design was employed with 2 groups and 3 assessment periods. The treatment group received an intervention designed to reduce current problems, but above all to prevent reinjury and minor pains from becoming chronic medical problems, and it included a physical and behavioral therapy package. The control group was placed on a waiting-list. Results indicated that the treatment group had significantly greater improvements than the control group for pain intensity, anxiety, sleep quality and fatigue ratings, observed pain behavior, activities, mood, and helplessness. These differences were generally maintained at the 6 month follow-up. In addition, the treatment group broke a trend for increasing amounts of pain-related absenteeism, while the control group did not. Taken as a whole, the results suggest that a secondary prevention program aimed at altering life style factors may represent an effective method for dealing with musculoskeletal pain problems.
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