| 1. |
- 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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| 2. |
- Alipour, Akbar, et al.
(författare)
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The transitional pattern of pain and disability, from perceived pain to sick leave : Experience from a longitudinal study
- 2013
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Ingår i: Journal of Back and Musculoskeletal Rehabilitation. - : IOS Press. - 1053-8127 .- 1878-6324. ; 26:4, s. 411-419
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: To investigate the prospective value of the transitional and dynamic patterns of pain disability over time on sick leave in chronic recurrent back/neck pain cases.Methods: The material used was based on a longitudinal study with three repeated measurements. The graded Chronic Pain Scale was used to assess levels of pain disability. The relationship between the transitional patterns of the pain disability score ( ten defined states of decrease, increase or no change, between two time points) and sick leave was analyzed for 909 chronic/recurrent cases in three different models using logistic regression. Results: Those with high level of pain disability have a more transitional pattern and their pain level changed during the time period studied. When adjusting for age, gender, education and previous sick leave, the final model indicated that the current level of pain disability was a risk factor in taking sick leave. The likelihood of sick leave was highest in the transition of pain into the highest levels of disability, independent of past disability level of pain. Earlier sick leave remained as an important predictor of sick leave.Conclusions: From a clinical and prognostic perspective the probability of sick leave will be different and can be predicted based on previous sick leave but not from former history of pain disability level or its transitional pattern.
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| 3. |
- 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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| 4. |
- Axén, Iben, et al.
(författare)
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Analyzing repeated data collected by mobile phones and frequent text messages : An example of Low back pain measured weekly for 18 weeks
- 2012
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Ingår i: BMC Medical Research Methodology. - : BioMed Central. - 1471-2288. ; 12
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Tidskriftsartikel (refereegranskat)abstract
- Background: Repeated data collection is desirable when monitoring fluctuating conditions. Mobile phones can be used to gather such data from large groups of respondents by sending and receiving frequently repeated short questions and answers as text messages.The analysis of repeated data involves some challenges. Vital issues to consider are the within-subject correlation, the between measurement occasion correlation and the presence of missing values.The overall aim of this commentary is to describe different methods of analyzing repeated data. It is meant to give an overview for the clinical researcher in order for complex outcome measures to be interpreted in a clinically meaningful way.Methods: A model data set was formed using data from two clinical studies, where patients with low back pain were followed with weekly text messages for 18 weeks. Different research questions and analytic approaches were illustrated and discussed, as well as the handling of missing data. In the applications the weekly outcome “number of days with pain” was analyzed in relation to the patients’ “previous duration of pain” (categorized as more or less than 30 days in the previous year).Research questions with appropriate analytical methods1: How many days with pain do patients experience? This question was answered with data summaries.2: What is the proportion of participants “recovered” at a specific time point? This question was answered using logistic regression analysis.3: What is the time to recovery? This question was answered using survival analysis, illustrated in Kaplan-Meier curves, Proportional Hazard regression analyses and spline regression analyses.4: How is the repeatedly measured data associated with baseline (predictor) variables? This question was answered using generalized Estimating Equations, Poisson regression and Mixed linear models analyses.5: Are there subgroups of patients with similar courses of pain within the studied population?A visual approach and hierarchical cluster analyses revealed different subgroups using subsets of the model data.Conclusions: We have illustrated several ways of analysing repeated measures with both traditional analytic approaches using standard statistical packages, as well as recently developed statistical methods that will utilize all the vital features inherent in the data.
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| 5. |
- Axén, Iben, et al.
(författare)
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Clustering patients on the basis of their individual course of low back pain over a six month period
- 2011
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Ingår i: BMC Musculoskeletal Disorders. - : BioMed Central. - 1471-2474. ; 12
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Tidskriftsartikel (refereegranskat)abstract
- Background: Several researchers have searched for subgroups in the heterogeneous population of patients with non-specific low back pain (LBP). To date, subgroups have been identified based on psychological profiles and the variation of pain.Methods: This multicentre prospective observational study explored the 6- month clinical course with measurements of bothersomeness that were collected from weekly text messages that were sent by 176 patients with LBP. A hierarchical cluster analysis, Ward's method, was used to cluster patients according to the development of their pain.Results: Four clusters with distinctly different clinical courses were described and further validated against clinical baseline variables and outcomes. Cluster 1, a "stable" cluster, where the course was relatively unchanged over time, contained young patients with good self- rated health. Cluster 2, a group of "fast improvers" who were very bothered initially but rapidly improved, consisted of patients who rated their health as relatively poor but experienced the fewest number of days with bothersome pain of all the clusters. Cluster 3 was the "typical patient" group, with medium bothersomeness at baseline and an average improvement over the first 4-5 weeks. Finally, cluster 4 contained the "slow improvers", a group of patients who improved over 12 weeks. This group contained older individuals who had more LBP the previous year and who also experienced most days with bothersome pain of all the clusters.Conclusions: It is possible to define clinically meaningful clusters of patients based on their individual course of LBP over time. Future research should aim to reproduce these clusters in different populations, add further clinical variables to distinguish the clusters and test different treatment strategies for them.
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| 6. |
- Axén, Iben, et al.
(författare)
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The use of weekly text messaging over 6 months was a feasible method for monitoring the clinical course of low back pain in patients seeking chiropractic care
- 2012
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Ingår i: Journal of Clinical Epidemiology. - : Elsevier. - 0895-4356 .- 1878-5921. ; 65:4, s. 454-461
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Tidskriftsartikel (refereegranskat)abstract
- Objective: This study critically evaluates a new method of collecting frequent data using mobile phones and text messages. Fluctuating conditions such as low back pain (LBP) need frequent monitoring to describe the clinical course in detail and to account for individual and subgroup variations.Study Design and Setting: In this multicentre prospective observational study, 262 subjects with nonspecific LBP were followed with weekly text messages for 6 months, with the question “How many days this previous week has your low back pain been bothersome?” The text replies were instantly recorded in a data file to be merged with baseline and follow up data (age, gender, pain intensity, duration, and self- rated health) collected through ordinary questionnaires. The response rate, user-friendliness, and compliance of this method were evaluated.Results: The mean response rate for the text messages throughout the study was 82.5% and was unaffected by season. The method was found to be user friendly. Dropout was not affected by age and gender, but compliance was possibly somewhat affected by outcome.Conclusion: Weekly text messages are a useful method of data collection to examine the clinical course of LBP in the primary care sector.
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| 7. |
- Bergström, Cecilia, et al.
(författare)
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Using a psychosocial subgroup assignment to predict sickness absence in a working population with neck and back pain
- 2011
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Ingår i: BMC Musculoskeletal Disorders. - : BioMed Central. - 1471-2474. ; 12
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Tidskriftsartikel (refereegranskat)abstract
- Background: The overall objective was to evaluate the predictive validity of a subgroup classification based on the Swedish version of the MPI, the MPI-S, among gainfully employed workers with neck pain (NP) and/or low back pain (LBP) during a follow-up period of 18 and 36 months.Methods: This is a prospective cohort study that is part of a larger longitudinal multi-centre study entitled Work and Health in the Process and Engineering Industries (AHA). The attempt was to classify individuals at risk for developing chronic disabling NP and LBP. This is the first study using the MPI-questionnaire in a working population with NP and LBP.Results: Dysfunctional individuals (DYS) demonstrated more statistically significant sickness absence compared to adaptive copers (AC) after 36 months. DYS also had a threefold increase in the risk ratio of long-term sickness absence at 18 months. Interpersonally distressed (ID) subgroup showed overall more sickness absence compared to the AC subgroup at the 36-month follow-up and had a twofold increase in the risk ratio of long-term sickness absence at 18 months. There was a significant difference in bodily pain, mental and physical health for ID and DYS subgroups compared to the AC group at both follow-ups.Conclusions: The present study shows that this multidimensional approach to the classification of individuals based on psychological and psychosocial characteristics can distinguish different groups in gainfully employed working population with NP/LBP. The results in this study confirm the predictive validity of the MPI-S subgroup classification system.
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| 8. |
- Bergström, Gunnar, et al.
(författare)
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A 7-year follow-up of multidisciplinary rehabilitation among chronic neck and back pain patients : Is sick leave outcome dependent on psychologically derived patient groups?
- 2010
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Ingår i: European Journal of Pain. - : Elsevier. - 1090-3801 .- 1532-2149. ; 14:4, s. 426-433
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Tidskriftsartikel (refereegranskat)abstract
- A valid method for classifying chronic pain patients into more homogenous groups could be useful for treatment planning, that is, which treatment is effective for which patient, and as a marker when evaluating treatment outcome. One instrument that has been used to derive subgroups of patients is the Multidimensional Pain Inventory (MPI). The primary aim of this study was to evaluate a classification method based on the Swedish version of the MPI, the MPI-S, to predict sick leave among chronic neck and back pain patients for a period of 7 years after vocational rehabilitation. As hypothesized, dysfunctional patients (DYS), according to the MPI-S, showed a higher amount of sickness absence and disability pension expressed in days than adaptive copers (AC) during the 7-years follow-up period, even when adjusting for sickness absence prior to rehabilitation (355.8days, 95% confidence interval, 71.7; 639.9). Forty percent of DYS patients and 26.7% of AC patients received disability pension during the follow-up period. However, this difference was not statistically significant. Further analyses showed that the difference between patient groups was most pronounced among patients with more than 60days of sickness absence prior to rehabilitation. Cost-effectiveness calculations indicated that the DYS patients showed an increase in production loss compared to AC patients. The present study yields support for the prognostic value of this subgroup classification method concerning long-term outcome on sick leave following this type of vocational rehabilitation.
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| 9. |
- Bohman, Tony, et al.
(författare)
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Does a healthy lifestyle behaviour influence the prognosis of low back pain among men and women in a general population? A population-based cohort study
- 2014
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Ingår i: BMJ Open. - : BMJ. - 2044-6055. ; 4:12
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES:To study the influence of healthy lifestyle behaviour on the prognosis of occasional low back pain among men and women in a general population.DESIGN:Cohort study with a 4-year follow-up.SETTINGS:General population in Stockholm County, Sweden.PARTICIPANTS:The study sample comprised 3938 men and 5056 women aged 18-84 from the Stockholm Public Health Cohort reporting occasional low back pain in the baseline questionnaire 2006.MEASURES:Lifestyle factors and potential confounders were assessed at baseline. The lifestyle factors smoking habits, alcohol consumption, leisure physical activity and consumption of fruit and vegetables were dichotomised using recommendations for a health-enhancing lifestyle and combined to form the exposure variable 'healthy lifestyle behaviour'. The exposure was categorised into five levels according to the number of healthy lifestyle factors met. The follow-up questionnaire in 2010 gave information about the outcome, long duration troublesome low back pain. Crude and adjusted binomial regression models were applied to estimate the association between the exposure and the outcome analysing men and women separately.RESULTS:The risk of developing long duration troublesome low back pain among women with occasional low back pain decreased with increasing healthy lifestyle behaviour (trend test: p=0.006). 21% (28/131) among women with no healthy lifestyle factor (reference) experienced the outcome compared to 9% (36/420) among women with all four factors. Compared to the reference group, the risk was reduced by 35% (RR 0.65, 95% CI 0.44 to 0.96) for women with one healthy lifestyle factor and 52% (RR 0.48, 95% CI 0.31 to 0.77) for women with all four healthy lifestyle factors. There were no clear associations found among men.CONCLUSIONS:Healthy lifestyle behaviour seems to decrease the risk of developing long duration troublesome low back pain among women with occasional low back pain and may be recommended to improve the prognosis.
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| 10. |
- 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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