| 1. |
- Adolfsson, Jan, et al.
(författare)
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Clinical characteristics and primary treatment of prostate cancer in Sweden between 1996 and 2005
- 2007
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Ingår i: Scandinavian Journal of Urology and Nephrology. - : Informa UK Limited. - 0036-5599 .- 1651-2065. ; 41:6, s. 456-477
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: The incidence of prostate cancer is rising rapidly in Sweden and there is a need to better understand the pattern of diagnosis, tumor characteristics and treatment. MATERIAL AND METHODS: Between 1996 and 2005, all new cases of adenocarcinoma of the prostate gland were intended to be registered in the National Prostate Cancer Register (NPCR). This register contains information on diagnosing unit, date of diagnosis, cause of diagnosis, tumor grade, tumor stage according to the TNM classification in force, serum prostate-specific antigen (PSA) levels at diagnosis and primary treatment given within the first 6 months after diagnosis. RESULTS: In total, 72,028 patients were registered, comprising >97% of all pertinent incident cases of prostate cancer in the Swedish Cancer Register (SCR). During the study period there was a considerable decrease in median age at the time of diagnosis, a stage migration towards smaller tumors, a decrease in median serum PSA values at diagnosis, a decrease in the age-standardized incidence rate of men diagnosed with distant metastases or with a PSA level of > 100 ng/ml at diagnosis and an increase in the proportion of tumors with Gleason score <6. Relatively large geographical differences in the median age at diagnosis and the age-standardized incidence of cases with category T1c tumors were observed. Treatment with curative intent increased dramatically and treatment patterns varied according to geographical region. In men with localized tumors and a PSA level of <20 ng/ml at diagnosis, expectant treatment was more commonly used in those aged > or =75 years than in those aged <75 years. Also, the pattern of endocrine treatment varied in different parts of Sweden. CONCLUSIONS: All changes in the register seen over time are consistent with increased diagnostic activity, especially PSA testing, resulting in an increased number of cases with early disease, predominantly tumors in category T1c. The patterns of diagnosis and treatment of prostate cancer vary considerably in different parts of Sweden. The NPCR continues to be an important source for research, epidemiological surveillance of the incidence, diagnosis and treatment of prostate cancer.
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| 2. |
- Malmberg, Erik, et al.
(författare)
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Patient-tailored analysis of minimal residual disease in acute myeloid leukemia using next-generation sequencing
- 2017
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Ingår i: European Journal of Haematology. - : Wiley. - 0902-4441 .- 1600-0609. ; 98:1, s. 26-37
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Tidskriftsartikel (refereegranskat)abstract
- Next-generation sequencing techniques have revealed that leukemic cells in acute myeloid leukemia often are characterized by a limited number of somatic mutations. These mutations can be the basis for the detection of leukemic cells in follow-up samples. The aim of this study was to identify leukemia-specific mutations in cells from patients with acute myeloid leukemia and to use these mutations as markers for minimal residual disease. Leukemic cells and normal lymphocytes were simultaneously isolated at diagnosis from 17 patients with acute myeloid leukemia using fluorescence-activated cell sorting. Exome sequencing of these cells identified 240 leukemia-specific single nucleotide variations and 22 small insertions and deletions. Based on estimated allele frequencies and their accuracies, 191 of these mutations qualified as candidates for minimal residual disease analysis. Targeted deep sequencing with a significance threshold of 0.027% for single nucleotide variations and 0.006% for NPM1 type A mutation was developed for quantification of minimal residual disease. When tested on follow-up samples from a patient with acute myeloid leukemia, targeted deep sequencing of single nucleotide variations as well as NPM1 was more sensitive than minimal residual disease quantification with multiparameter flow cytometry. In conclusion, we here describe how exome sequencing can be used for identification of leukemia-specific mutations in samples already at diagnosis of acute myeloid leukemia. We also show that targeted deep sequencing of such mutations, including single nucleotide variations, can be used for high-sensitivity quantification of minimal residual disease in a patient-tailored manner.
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| 3. |
- Bergemalm, Daniel, 1977-, et al.
(författare)
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Systemic Inflammation in Preclinical Ulcerative Colitis
- 2021
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Ingår i: Gastroenterology. - : AGA Institute. - 0016-5085 .- 1528-0012. ; 161:5, s. 1526-1539.e9
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Tidskriftsartikel (refereegranskat)abstract
- Background & Aims: Preclinical ulcerative colitis is poorly defined. We aimed to characterize the preclinical systemic inflammation in ulcerative colitis, using a comprehensive set of proteins.Methods: We obtained plasma samples biobanked from individuals who developed ulcerative colitis later in life (n = 72) and matched healthy controls (n = 140) within a population-based screening cohort. We measured 92 proteins related to inflammation using a proximity extension assay. The biologic relevance of these findings was validated in an inception cohort of patients with ulcerative colitis (n = 101) and healthy controls (n = 50). To examine the influence of genetic and environmental factors on these markers, a cohort of healthy twin siblings of patients with ulcerative colitis (n = 41) and matched healthy controls (n = 37) were explored.Results: Six proteins (MMP10, CXCL9, CCL11, SLAMF1, CXCL11 and MCP-1) were up-regulated (P < .05) in preclinical ulcerative colitis compared with controls based on both univariate and multivariable models. Ingenuity Pathway Analyses identified several potential key regulators, including interleukin-1β, tumor necrosis factor, interferon-gamma, oncostatin M, nuclear factor-κB, interleukin-6, and interleukin-4. For validation, we built a multivariable model to predict disease in the inception cohort. The model discriminated treatment-naïve patients with ulcerative colitis from controls with leave-one-out cross-validation (area under the curve = 0.92). Consistently, MMP10, CXCL9, CXCL11, and MCP-1, but not CCL11 and SLAMF1, were significantly up-regulated among the healthy twin siblings, even though their relative abundances seemed higher in incident ulcerative colitis.Conclusions: A set of inflammatory proteins are up-regulated several years before a diagnosis of ulcerative colitis. These proteins were highly predictive of an ulcerative colitis diagnosis, and some seemed to be up-regulated already at exposure to genetic and environmental risk factors.
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| 4. |
- Bergsten, Eva L., 1969-, et al.
(författare)
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Physical and psychosocial work conditions among baggage handlers in six Swedish airports
- 2012
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Konferensbidrag (refereegranskat)abstract
- Introduction Flight baggage handlers are mainly engaged in sorting luggage or cargo, loading and unloading it to and from the airplanes. The Vocational Training and Working Environment Council, TYA - formed by employer’s and employee’s organizations in the transportation sector - initiated a scientific study in 2009 to investigate the prevalence of musculoskeletal disorders and their suspected determinants in six Swedish airports involving a total of about 1000 handlers in 14 cargo- and handling companies. Encouraged by an initial literature review, the present field study was designed to contain qualitative, questionnaire-based, and observational surveys of working conditions, as well as extensive direct measurements of postures using full-shift inclinometry. This paper reports the design and results of the questionnaire part of the study.MethodAll baggage handlers working at least half-time (n=1044) were encouraged to fill in an extensive questionnaire handed out at the workplace by a research team member. In general the researcher collected the questionnaires at the same occasion. The questionnaire addressed general health, work capacity and physical exposures in relevant handling tasks. It also included a modified version of the Copenhagen Psychosocial Questionnaire (COPSOQ), the Nordic Council of Minister’s Questionnaire (NMQ) on disorders, and the SOFI-questionnaire measuring perceived fatigue.ResultsThe response rate was 73%. The prevalence of musculoskeletal disorders in the back, shoulders and wrists during the last 12 months was 70%, 60% and 45%. Positive effects of devices used for reducing perceived physical load were confirmed. The handlers expressed a low confidence in the leadership, and insufficient feedback, information and influence at work. Fatigue particularly occurred in the dimensions lack of energy and physical discomfort.DiscussionThe observed prevalence of low back pain (70%) is high, and in parity with results among nurses in Sweden (64%; Josephson et al. 1997) and China (56%; Smith et al. 2004). Further examination of questionnaires, interviews and direct posture measurements will identify determinants to consider for intervention to reduce the prevalence of disorders among the baggage handlers.Josephson M, et al. Occup Environ Med 1997;54:681-685.Smith DR, et al. Occup Med 2004;54:579-582
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| 5. |
- Lindgren, Marie, 1971, et al.
(författare)
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Survival and risk of vascular complications in myelofibrosis—A population-based study from the Swedish MPN group
- 2022
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Ingår i: European Journal of Haematology. - : Wiley. - 0902-4441 .- 1600-0609. ; 109:4, s. 336-342
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To gain knowledge of underlying risk factors for vascular complications and their impact on life expectancy in myelofibrosis. Methods: From a cohort of 392 myelofibrosis patients registered in the Swedish MPN registry 58 patients with vascular complications during follow-up were identified. Patients with vascular complications were compared with both 1:1 matched controls and the entire myelofibrosis cohort to explore potential risk factors for vascular complications and their impact on survival. Results: Incidence of vascular complications was 2.8 events per 100 patient-years and the majority of complications were thrombotic. Patients with complications were significantly older and had lower hemoglobin when compared to the entire cohort. In the case–control analysis, no significant risk factor differences were observed. The major cause of death was vascular complications and median survival was significantly impaired in patients with vascular complications (48 months) compared to controls (92 months). Inferior survival in patients with vascular complications was found to be dependent on IPSS risk category in a Cox regression model. Conclusion: Vascular complications have a considerable impact on survival in MF. At diagnosis, risk assessment by IPSS does not only predict survival but is also associated with the risk of vascular complications.
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| 6. |
- Zheng, Hou-Feng, et al.
(författare)
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Whole-genome sequencing identifies EN1 as a determinant of bone density and fracture
- 2015
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 526:7571, s. 112-
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Tidskriftsartikel (refereegranskat)abstract
- The extent to which low-frequency (minor allele frequency (MAF) between 1-5%) and rare (MAF <= 1%) variants contribute to complex traits and disease in the general population is mainly unknown. Bone mineral density (BMD) is highly heritable, a major predictor of osteoporotic fractures, and has been previously associated with common genetic variants(1-8), as well as rare, population specific, coding variants(9). Here we identify novel non-coding genetic variants with large effects on BMD (n(total) = 53,236) and fracture (n(total) = 508,253) in individuals of European ancestry from the general population. Associations for BMD were derived from whole-genome sequencing (n = 2,882 from UK10K (ref. 10); a population-based genome sequencing consortium), whole-exome sequencing (n = 3,549), deep imputation of genotyped samples using a combined UK10K/1000 Genomes reference panel (n = 26,534), and de novo replication genotyping (n = 20,271). We identified a low-frequency non-coding variant near a novel locus, EN1, with an effect size fourfold larger than the mean of previously reported common variants for lumbar spine BMD8 (rs11692564(T), MAF51.6%, replication effect size510.20 s.d., P-meta = 2 x 10(-14)), which was also associated with a decreased risk of fracture (odds ratio = 0.85; P = 2 x 10(-11); ncases = 98,742 and ncontrols = 409,511). Using an En1cre/flox mouse model, we observed that conditional loss of En1 results in low bone mass, probably as a consequence of high bone turnover. We also identified a novel low frequency non-coding variant with large effects on BMD near WNT16 (rs148771817(T), MAF = 1.2%, replication effect size +10.41 s.d., P-meta = 1 x 10(-11)). In general, there was an excess of association signals arising from deleterious coding and conserved non-coding variants. These findings provide evidence that low-frequency non-coding variants have large effects on BMD and fracture, thereby providing rationale for whole-genome sequencing and improved imputation reference panels to study the genetic architecture of complex traits and disease in the general population.
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| 7. |
- Franzén, Karin, 1958-, et al.
(författare)
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Urinary incontinence in women is not exclusively a medical problem : a population-based study on urinary incontinence and general living conditions
- 2009
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Ingår i: Scandinavian Journal of Urology and Nephrology. - London : Taylor & Francis. - 0036-5599 .- 1651-2065. ; 43:3, s. 226-232
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: The aim of the study was to analyse differences in general health and general living conditions between women with and without urinary incontinence (UI).MATERIAL AND METHODS: This cross-sectional population-based study was conducted in Orebro County, Sweden. A public health questionnaire, "Life and Health", was sent to a randomly selected sample of the population. The questionnaire consisted of 87 questions on broad aspects of general and psychiatric health. An additional questionnaire was enclosed for those respondents who reported experiencing UI. The data were analysed using binary logistic regression. The final study population constituted 4609 women, 1332 of whom had completed both questionnaires. The remaining 3277 had completed only the Life and Health questionnaire. Effect measures were odds ratios (ORs) with corresponding 95% confidence intervals (CIs).RESULTS: Statistically significant associations were found between UI and the occurrence of musculoskeletal pain (OR 1.45, 95% CI 1.20-1.76), fatigue and sleeping disorders (OR 1.59, 95% CI 1.30-1.95), feelings of humiliation (OR 1.29, 95% CI 1.12-1.50), financial problems (OR 1.36, 95% CI 1.11-1.66), and reluctance to seek medical care (OR 1.43, 95% CI 1.21-1.68).CONCLUSION: UI among women is commonly associated with a number of different psychosocial problems as well as an expressed feeling of vulnerability.
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| 8. |
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| 9. |
- Pettersson, Beatrice, et al.
(författare)
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Effectiveness of a self-managed digital exercise programme to prevent falls in older community-dwelling adults : study protocol for the Safe Step randomised controlled trial
- 2020
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Ingår i: BMJ Open. - : BMJ Publishing Group Ltd. - 2044-6055. ; 10:5
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: Exercise interventions have a strong evidence base for falls prevention. However, exercise can be challenging to implement and often has limited reach and poor adherence. Digital technology provides opportunities for both increased access to the intervention and support over time. Further knowledge needs to be gained regarding the effectiveness of completely self-managed digital exercise interventions. The main objective of this study is to compare the effectiveness of a self-managed digital exercise programme, Safe Step, in combination with monthly educational videos with educational videos alone, on falls over 1 year in older community-dwelling adults.Methods and analysis: A two-arm parallel randomised controlled trial will be conducted with at least 1400 community-living older adults (70+ years) who experience impaired balance. Participants will be recruited throughout Sweden with enrolment through the project website. They will be randomly allocated to either the Safe Step exercise programme with additional monthly educational videos about healthy ageing and fall prevention, or the monthly education videos alone. Participants receiving the exercise intervention will be asked to exercise at home for at least 30 min, 3 times/week with support of the Safe Step application. The primary outcome will be rate of falls (fall per person year). Participants will keep a fall calendar and report falls at the end of each month through a digital questionnaire. Further assessments of secondary outcomes will be made through self-reported questionnaires and a self-test of 30 s chair stand test at baseline and 3, 6, 9 and 12 months after study start. Data will be analysed according to the intention-to-treat principle.Ethics and dissemination: Ethical approval was obtained by The Regional Ethical Review Board in Umeå (Dnr 2018/433-31). Findings will be disseminated through the project web-site, peer-reviewed journals, national and international conferences and through senior citizen organisations’ newsletters.Trial registration number: NCT03963570.
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