| 1. |
- Lehtinen-Jacks, Susanna, et al.
(författare)
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Serum 25-hydroxy vitamin D levels in middle-aged women in relationship to adiposity and height trajectories over three decades
- 2016
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Ingår i: European Journal of Clinical Nutrition. - : Springer Science and Business Media LLC. - 0954-3007 .- 1476-5640. ; 70:6, s. 709-14
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND/OBJECTIVES: The long-term chronology of the association between low serum concentrations of 25-hydroxy vitamin D (25(OH)D) and weight status is unclear. We examined whether lower 25(OH)D in middle-aged women drives upwards the weight, body mass index (BMI) and waist-hip ratio (WHR) over the next 32 years, and whether higher 25(OH)D might predict less decline in the mid- to late-life height trajectory. SUBJECTS/METHODS: The Population Study of Women in Gothenburg started in 1968-1969 (the baseline) in 38-60-year-old women residing in Gothenburg, Sweden. Anthropometric measures were taken at baseline and 4 re-examinations until 2000-2003. Levels of 25(OH)D were analyzed in serum stored since baseline in 1227 (84%) women. Repeated measures analyses were used to model associations between 25(OH)D (dichotomized, cut point 51.45nmol/l) at baseline and anthropometric trajectories, adjusting for fixed and time-dependent covariates. RESULTS: At baseline, mean BMI was 25.2kg/m2 in women with low 25(OH)D and 23.8kg/m2 in the remaining women (P<0.001), but this difference did not increase over 32 years and longitudinal differences were explained by the baseline BMI. Similar results were observed for weight and WHR. In contrast, no association was seen for height at baseline or longitudinally. CONCLUSIONS: No relationship was observed between 25(OH)D height trajectory, but lower 25(OH)D was associated with higher BMI, weight and WHR differences that were maintained over three decades. This provides no evidence for the direction of causality, but for a life-long difference in adiposity-related measures according to the 25D level in middle-aged women.
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| 2. |
- Leu, Monica, 1977, et al.
(författare)
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Quality Assessment of 25(OH)D, Insulin, Total Cholesterol, Triglycerides, and Potassium in 40-Year-Old Frozen Serum
- 2015
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Ingår i: Epidemiology Research International. - : Hindawi Limited. - 2090-2980 .- 2090-2972. ; 2015
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Tidskriftsartikel (refereegranskat)abstract
- Background: Many longitudinal epidemiological studies collect specimens into biobanks to investigate how biomarkers predict future disease. In 1968-1969, the Population Study of Women in Gothenburg (PSWG) established a biobank. Objective: To examine the validity of 25-hydroxyvitamin D (25(OH)D), total cholesterol, triglycerides, insulin and potassium after 40 years of storage at -20⁰C in terms of relative and absolute agreement. The quality of these markers under such condition has not been previously investigated. Methods: Baseline- and re-measured levels were compared in selected samples through percentage change, correlation and regression. 25(OH)D levels, not assessed at baseline, were compared by season, by BMI and longitudinally over six years. Results: Despite some lack of absolute agreement, Spearman correlations were >0.7 and statistically significant for all biomarkers. The 1968-1969 25(OH)D correlated with BMI (r=-0.45, p=0.05) and with levels six years later (r=0.85, p<0.001). Summer 25(OH)D was higher than winter 25(OH)D (p=0.02). Conclusion: For all markers, baseline- and re-measured levels exhibited high relative agreement. 25(OH)D was comparable with expected levels on fresh blood and varied with season. In future studies, PSWG individuals will be ranked according to these markers in order to follow incidence of disease.
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| 3. |
- Andersson, Maria L.E., et al.
(författare)
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Autoantibodies to Disease-Related Proteins in Joints as Novel Biomarkers for the Diagnosis of Rheumatoid Arthritis
- 2023
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Ingår i: Arthritis & Rheumatology. - : Wiley. - 2326-5191 .- 2326-5205. ; 75:7, s. 1110-1119
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Tidskriftsartikel (refereegranskat)abstract
- Objective. This study was undertaken to develop and characterize a multiplex immunoassay for detection of autoantibodies against peptides derived from proteins known to play a role in development of arthritis and that are also expressed in joints.Methods. We selected peptides from the human counterpart of proteins expressed in the joints, based on mouse models that showed these to be targeted by pathogenic or regulatory antibodies in vivo. Using bead-based flow immunoassays measuring IgG antibodies, we selected triple helical or cyclic peptides, containing the epitopes, to avoid collinear reactivity. We characterized the analytical performance of the immunoassay and then validated it in 3 independent rheumatoid arthritis (RA) cohorts (n = 2,110), Swedish age- and sex-matched healthy controls, and patients with osteoarthritis (OA), patients with psoriatic arthritis (PsA), and patients with systemic lupus erythematosus (SLE).Results. Screening assays showed 5 peptide antigens that discriminated RA patients from healthy controls with 99% specificity (95% confidence interval [CI] 98-100%). In our validation studies, we reproduced the discriminatory capacity of the autoantibodies in 2 other RA cohorts, showing that the autoantibodies had high discriminatory capacity for RA versus OA, PsA, and SLE. The novel biomarkers identified 22.5% (95% CI 19-26%) of early RA patients seronegative for anti-cyclic citrullinated peptide and rheumatoid factor. The usefulness of the biomarkers in identifying seronegative RA patients was confirmed in validation studies using 2 independent cohorts of RA patients and cohorts of patients with OA, PsA, and SLE.Conclusion. A multiplex immunoassay with peptides from disease-related proteins in joints was found to be useful for detection of specific autoantibodies in RA serum. Of note, this immunoassay had high discriminatory capacity for early seronegative RA.
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| 4. |
- Brann, Ebba, et al.
(författare)
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Declining Well-Being in Young Swedes Born in 1990 Versus 1974
- 2017
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Ingår i: The Journal of adolescent health : official publication of the Society for Adolescent Medicine. - : Elsevier BV. - 1879-1972. ; 60:3, s. 306-312
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Tidskriftsartikel (refereegranskat)abstract
- Well-being is affected by the environment, including societal changes. In this study, specific dimensions of well-being were compared in two cohorts of Swedish adolescents born 16years apart.Two groups of 18-year-olds, "Grow up Gothenburg" 1974 and 1990 birth cohorts, completed a self-reported questionnaire including the Gothenburg Well-Being in adolescence scale (GWBa). In addition, height and weight were measured, resulting in 4,362 participants (1974 birth cohort) and 5,151 participants (1990 birth cohort) with age, height, weight, and well-being data. The GWBa consists of a total score and five dimensions: mood, physical condition, energy, self-esteem, and stress balance.Total well-being was significantly lower in the later-born cohort, and the greatest difference was seen for the dimension stress balance (feeling calm, unconcerned, unstressed, and relaxed), although effect sizes were modest. In both boys and girls, well-being was lower for all dimensions in the later-born cohort, with the exception of Self-esteem in girls, which was higher in the later-born cohort. In both cohorts, boys reported higher well-being than girls for all dimensions. The mean body mass index z-score was higher in boys from the later-born cohort, but after adjusting for weight status, the differences in well-being between the cohorts persisted.Well-being was lower in the later-born cohort, particularly for the dimension stress balance. Differences were not explained by the shift in weight status indicating that other societal changes have had an impact on well-being levels. Managing high levels of stress might be an area of intervention in adolescents for improved well-being.
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| 5. |
- Brann, Ebba, et al.
(författare)
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Evaluating the predictive ability of childhood body mass index classification systems for overweight and obesity at 18 years
- 2015
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Ingår i: Scandinavian Journal of Public Health. - : SAGE Publications. - 1403-4948 .- 1651-1905. ; 43:8, s. 802-9
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Tidskriftsartikel (refereegranskat)abstract
- AIM: To evaluate the performance of three childhood body mass index classification systems defining weight status at age 10, for predicting overweight and obesity at 18 years, according to the World Health Organization adult body mass index classification. METHODS: Weight and height of 4235 Swedish girls and boys were measured both at around ages 10 and 18 years. Predictive ability of the extended International Obesity Task Force body mass index cut-offs (2012), the World Health Organization body mass index-for-age (2007) and a Swedish body mass index reference (2001) were assessed for sensitivity and specificity. RESULTS: For predicting overweight including obesity at 18 years, the World Health Organization 2007 and the Swedish body mass index reference 2001 had similar sensitivity, 68% and 71%. The International Obesity Task Force 2012 had a significantly lower sensitivity, 53%. Specificity was 82-91% and highest for International Obesity Task Force 2012. For predicting obesity, the sensitivity for International Obesity Task Force 2012 was 29%, significantly lower than for the other two, 63% and 70%. Specificity was 94-100%, and highest for International Obesity Task Force 2012. CONCLUSIONS: In situations when optimal screening sensitivity is required for identifying as many high-risk children as possible, the World Health Organization 2007 and the Swedish body mass index reference 2001 performed better than the International Obesity Task Force 2012. However, it is important to keep in mind that the International Obesity Task Force 2012 will identify the fewest false positives.
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| 6. |
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| 7. |
- Bärebring, Linnea, et al.
(författare)
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Preeclampsia and Blood Pressure Trajectory during Pregnancy in Relation to Vitamin D Status
- 2016
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Ingår i: Plos One. - : Public Library of Science (PLoS). - 1932-6203. ; 11:3
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Tidskriftsartikel (refereegranskat)abstract
- Every tenth pregnancy is affected by hypertension, one of the most common complications and leading causes of maternal death worldwide. Hypertensive disorders in pregnancy include pregnancy-induced hypertension and preeclampsia. The pathophysiology of the development of hypertension in pregnancy is unknown, but studies suggest an association with vitamin D status, measured as 25-hydroxyvitamin D (25(OH) D). The aim of this study was to investigate the association between gestational 25(OH) D concentration and preeclampsia, pregnancy-induced hypertension and blood pressure trajectory. This cohort study included 2000 women. Blood was collected at the first (T1) and third (T3) trimester (mean gestational weeks 10.8 and 33.4). Blood pressure at gestational weeks 10, 25, 32 and 37 as well as symptoms of preeclampsia and pregnancy-induced hypertension were retrieved from medical records. Serum 25(OH) D concentrations (LC-MS/MS) in T1 was not significantly associated with preeclampsia. However, both 25(OH) D in T3 and change in 25 (OH) D from T1 to T3 were significantly and negatively associated with preeclampsia. Women with a change in 25(OH) D concentration of >= 30 nmol/L had an odds ratio of 0.22 (p = 0.002) for preeclampsia. T1 25(OH) D was positively related to T1 systolic (beta = 0.03, p = 0.022) and T1 diastolic blood pressure (beta = 0.02, p = 0.016), and to systolic (beta = 0.02, p = 0.02) blood pressure trajectory during pregnancy, in adjusted analyses. There was no association between 25(OH) D and pregnancy-induced hypertension in adjusted analysis. In conclusion, an increase in 25(OH) D concentration during pregnancy of at least 30 nmol/L, regardless of vitamin D status in T1, was associated with a lower odds ratio for preeclampsia. Vitamin D status was significantly and positively associated with T1 blood pressure and gestational systolic blood pressure trajectory but not with pregnancy-induced hypertension.
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| 8. |
- Gatto, Mariele, et al.
(författare)
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Early increase of circulating transitional B cells and autoantibodies to joint-related proteins in patients with metastatic melanoma developing checkpoint inhibitor-induced inflammatory arthritis.
- 2023
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Ingår i: Arthritis & rheumatology (Hoboken, N.J.). - : Wiley. - 2326-5205 .- 2326-5191. ; 75:5, s. 856-863
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Tidskriftsartikel (refereegranskat)abstract
- To investigate potential associations between B cell-related immunological changes and development of inflammatory arthritis (IA) after treatment with immune checkpoint inhibitors (ICI).Patients who developed IA (ICI-IA) and patients who did not develop immune-related adverse events (non-irAE) after receiving ICI due to metastatic melanoma were consecutively recruited. Blood samples were collected at the time of ICI-IA occurrence and at different timepoints during treatment. Peripheral blood B cell subsets during ICI treatment were analyzed by flow cytometry. Rheumatoid factor, autoantibodies against citrullinated peptides and against joint-related proteins were measured.Proportions of CD19+ B cells were higher in patients with ICI-IA (n=7) vs. non-irAE (n=15; median (interquartile range, IQR), %: 11.7 (9.7-16.2) vs. 8.1 (5.7-11.0), p=0.03). The proportion and absolute numbers of transitional CD19+ CD10+ CD24hi CD38hi B cells were increased in patients with ICI-IA vs. non-irAE (median (IQR); %: 8.1 (4.9-12.1) vs. 3.6 (1.9-4.9); cells/μl: 10.7 (8.9-19.6) vs. 4.4 (2.3-6.6), p<0.01 for both), and higher levels of transitional B cells were associated with development of ICI-IA (OR 95% CI: 2.25 (1.03-4.9), p=0.04). Transitional B cells increased before the onset of overt ICI-IA and decreased from active to quiescent ICI-IA (p=0.02). Autoantibodies to collagen II epitopes were detected in up to 43% of ICI-IA patients compared to none of the non-irAE patients (p=0.02).Development of ICI-IA is accompanied by an increase in transitional B cells and by production of autoantibodies to joint-related proteins. Monitoring of B cell-driven abnormalities upon ICI treatment may help earlier recognition of ICI-IA. This article is protected by copyright. All rights reserved.
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| 9. |
- Huseinovic, Ena, et al.
(författare)
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Effectiveness of a weight loss intervention in postpartum women: results from a randomized controlled trial in primary health care
- 2016
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Ingår i: American Journal of Clinical Nutrition. - : Elsevier BV. - 0002-9165. ; 104:2, s. 362-370
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Tidskriftsartikel (refereegranskat)abstract
- Background: Reproduction has been identified as an important factor for long-term weight gain among women. A previous efficacy trial has successfully produced postpartum weight loss; however, the effectiveness of this intervention needs to be established. Objective: This study was designed to evaluate the short-and long-term effectiveness of a diet behavior modification treatment to produce weight loss in postpartum women within the primary health care setting in Sweden. Design: During 2011-2014, 110 women with a self-reported body mass index (BMI; in kg/m(2)) of >= 27 at 6-15 wk postpartum were randomly assigned to the diet behavior modification group (D group) or the control group (C group). Women randomly assigned to the D group (n = 54) received a structured 12-wk diet behavior modification treatment by a dietitian and were instructed to gradually implement a diet plan based on the Nordic Nutrition Recommendations and to self-weigh >= 3 times/wk. Women randomly assigned to the C group (n = 56) were given a brochure on healthy eating. The primary outcome was change in body weight after 12 wk and 1 y. The retention rate was 91% and 85% at 12 wk and 1 y, respectively. Results: At baseline, women had a median (1st, 3rd quartile) BMI of 31.0 (28.8, 33.6), and 84% were breastfeeding. After 12 wk, median weight change in the D group was -6.1 kg (-8.4, -3.2 kg) compared with -1.6 kg (-3.5, -0.4 kg) in the C group (P < 0.001). The difference was maintained at the 1-y follow-up for the D group, -10.0 kg (-11.7, -5.9 kg) compared with 24.3 kg (-10.2, -1.0 kg) in the C group (P = 0.004). In addition, the D group reduced BMI, waist circumference, hip circumference, and body fat percentage more than did the C group at both 12 wk and 1 y (all P < 0.05). Conclusion: A low-intensity diet treatment delivered by a dietitian within the primary health care setting can produce clinically relevant and sustainable weight loss in postpartum women with overweight and obesity.
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| 10. |
- Leu Agelii, Monica, 1977, et al.
(författare)
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Disease activity trajectories in rheumatoid arthritis: a tool for prediction of outcome
- 2021
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Ingår i: Scandinavian Journal of Rheumatology. - : Informa UK Limited. - 0300-9742 .- 1502-7732. ; 501:1, s. 1-10
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Tidskriftsartikel (refereegranskat)abstract
- Objective Predicting treatment response and disease progression in rheumatoid arthritis (RA) remains an elusive endeavour. Identifying subgroups of patients with similar progression is essential for understanding what hinders improvement. However, this cannot be achieved with response criteria based on current versus previous Disease Activity Scores, as they lack the time component. We propose a longitudinal approach that identifies subgroups of patients while capturing their evolution across several clinical outcomes simultaneously (multi-trajectories). Method For exploration, the RA cohort BARFOT (n = 2829) was used to identify 24 month post-diagnosis simultaneous trajectories of 28-joint Disease Activity Score and its components. Measurements were available at inclusion (0), 3, 6, 12, 24, and 60 months. Multi-trajectories were found with latent class growth modelling. For validation, the TIRA-2 cohort (n = 504) was used. Radiographic changes, assessed by the modified Sharp van der Heijde score, were correlated with trajectory membership. Results Three multi-trajectories were identified, with 39.6% of the patients in the lowest and 18.9% in the highest (worst) trajectory. Patients in the worst trajectory had on average eight tender and six swollen joints after 24 months. Radiographic changes at 24 and 60 months were significantly increased from the lowest to the highest trajectory. Conclusion Multi-trajectories constitute a powerful tool for identifying subgroups of RA patients and could be used in future studies searching for predictive biomarkers for disease progression. The evolution and shape of the trajectories in TIRA-2 were very similar to those in BARFOT, even though TIRA-2 is a newer cohort.
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| 11. |
- Leu Agelii, Monica, 1977, et al.
(författare)
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Low vitamin D status in relation to cardiovascular disease and mortality in Swedish women - Effect of extended follow-up
- 2017
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Ingår i: Nutrition Metabolism and Cardiovascular Diseases. - : Elsevier BV. - 0939-4753 .- 1590-3729. ; 27:12, s. 1143-1151
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Tidskriftsartikel (refereegranskat)abstract
- Background and aims: The impact of vitamin D concentrations on subsequent cardiovascular disease (CVD) and overall mortality has been generally examined for periods under two decades. The magnitude of the association may depend on follow-up length. We aimed to investigate the relationship between baseline vitamin D and risk of total CVD, stroke and all-cause mortality over three decades of follow-up. Secondly, we aimed to assess how follow-up affects the associations. Methods and results: Concentrations of 25-hydroxyvitamin D (25D) were measured in a population-based sample of 1227 middle-aged women using serum collected at baseline and categorized into low (lowest 25D quartile) vs high 25D status (upper three 25D quartiles). Hazard ratio (HR) of the endpoints was estimated for low 25D. The impact of follow-up was examined in intermediary analyses where follow-up was interrupted up to four times, each time decreasing it by five years. There were 596 cardiovascular events and 635 participants died. During the first 17 years, the low 25D group experienced a 29% higher CVD risk and 3.3-fold higher stroke risk after accounting for confounders. Longer follow-up diminished significantly these risks and 25D status had no contribution at 32 years. For mortality, the decline over time was less dramatic, with HR = 1.96 (1.25; 3.08) at 17 years and HR = 1.42 (1.17; 1.72) at 37 years. Conclusion: Low 25D status increased the risk for all endpoints, but a lengthy follow-up diminished these risks towards the null. The impact of follow-up depends on the outcome. Future studies of 25D and disease should use repeated 25D assessments. (C) 2017 The Italian Society of Diabetology, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition, and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B. V. All rights reserved.
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| 12. |
- Leu Agelii, Monica, 1977, et al.
(författare)
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Misdiagnosis of Rheumatoid Arthritis in a Long-Term Cohort of Early Arthritis Based on the ACR-1987 Classification Criteria
- 2022
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Ingår i: Open Access Rheumatology-Research and Reviews. - 1179-156X. ; 14, s. 187-194
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Tidskriftsartikel (refereegranskat)abstract
- Objective: Correct diagnosis of early rheumatoid arthritis (RA) is essential for optimal treatment choices. No pathognomonic test is available, and diagnosis is based on classification criteria, which can result in misdiagnosis. Here, we examined the differences between actual and misdiagnosed RA cases in a long-term cohort of patients included based on the ACR-1987 classification criteria.Methods: Patients in the BARFOT (Better Anti-Rheumatic PharmacOTherapy) cohort (n=2543) with at least four follow-up visits during the initial 5 years from enrolment were assessed, and a change in diagnosis was reported by the treating rheumatologist. The groups were analysed with respect to the individual classification criteria, antibodies to citrullinated proteins (ACPA), disease activity (DAS28) and radiographic changes from inclusion up to 2 years.Results: Forty-five patients (1.8%) were misdiagnosed (RA-change group). When compared to those in the RA-change group, the patients who kept their diagnosis (RA-keep) were more often RF positive (64% vs 21%, p<0.001) or ACPA positive (59% vs 8%, p<0.001). They were also more likely to fulfil more than four ACR-1987 criteria (64% vs 33%, p<0.001) and to have radiographic changes at inclusion (RA-keep 27% vs RA-change 12%, p=0.04). The groups had a similar evolution of DAS28 and its components as well as of radiological joint destruction.Conclusion: Diagnosis of RA according to the ACR-1987 criteria had a high precision in this long-term cohort. A diagnosis of RA should be re-evaluated in patients who do not fulfil more than four ACR-1987 criteria especially in patients negative for RF.
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| 13. |
- Leu, Monica, 1977, et al.
(författare)
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Bias and bias-correction of estimates of familial risk in population-based register
- 2009
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Ingår i: International Journal of Epidemiology. - 0300-5771. ; 39:1, s. 80-8
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Tidskriftsartikel (refereegranskat)abstract
- Background In addition to guiding molecular epidemiology investigations, estimates of the increased risk of disease in relatives of affected persons are also important for screening and counselling decisions. Since precise estimation of such familial risks (FRs) requires large sample sizes, many of the estimates in common use have been obtained from historical electronic records of disease in entire populations, where the relatives of affected and unaffected persons are compared. These estimates may be biased due to failure to identify relatives as affected if they are diagnosed before the start-up date of disease registration. Methods This article presents a method for correcting the bias in FR estimates from such misclassification of family history, using a simple formula that depends on the prevalence and sensitivity of the observed family history. The sensitivity is estimated by using the R package poplab to create realistic populations of related individuals and then imposing the start-up effect of disease registration. Results For a range of FRs, the truncation of family history is demonstrated to result in non-differential misclassification, and sensitivity that has little or no dependence on the FR. The bias is most pronounced for high FRs and for registers with a short life span, and increases with the age of the study cohort. In all the situations studied, the bias-corrected estimates are in excellent agreement with the true values. Conclusions In summary, our method can correct the inevitable bias in FRs induced by using electronic population data, and is a feasible alternative to the use of validation samples.
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| 14. |
- Leu, Monica, 1977, et al.
(författare)
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Evaluation of bias in familial risk estimates: a study of common cancers using Swedish population-based registers
- 2008
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Ingår i: Journal of the National Cancer Institute. - 0027-8874. ; 100:18, s. 1318-25
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Tidskriftsartikel (refereegranskat)abstract
- Background Bias in estimates of familial cancer may result if population-based registers fail to identify relatives as affected when disease occurs before the start-up of registration (ie, “left-truncation” of family history). Methods Apparent familial relative risks (among offspring of parents with cancer) of colorectal, lung, breast, and prostate cancers and melanoma in a Swedish cohort were compared with relative risks in a simulated population. The study cohort (approximately 7 million individuals) was based on the Swedish MultiGenerational Register linked to the Swedish Cancer Register for the period 1961–2002. A similar population of related individuals (approximately 7 million) with complete family information was simulated by using the R-package PopLab and used to estimate the sensitivity of the observed family history. This sensitivity was then used to calculate corrected age group–specific and overall risks, which were compared with the apparent familial risks of cancer in the cohort. Result The apparent familial risks for colorectal, lung, breast, and prostate cancers and melanoma were 1.99 (95% confidence interval [CI]=1.85 to 2.14), 2.05 (95% CI=1.86 to 2.26), 1.84 (95% CI=1.76 to 1.92), 2.33 (95% CI=2.19 to 2.48), and 2.68 (95% CI=2.35 to 3.07), with corresponding absolute rates of 3.69, 2.59, 16.05, 10.38, and 2.96 per 10000 person-years, among offspring of parents diagnosed with the same cancer. Corrected age group–specific and overall estimates of the familial risks were close to these apparent risks for all studied cancers (all approximately 2.0), except for melanoma. For melanoma, the corrected estimate of 3.18 (95% CI=2.73 to 3.64) was somewhat larger than the apparent estimate and was not included in the confidence interval for the apparent estimate. When the exposure of interest was a parent affected at a younger age, this bias was more pronounced; the apparent estimate for melanoma changed from 4.07 (95% CI=3.21 to 5.16) to 5.67 (95% CI=4.51 to 6.83) after correction. Conclusions For common cancers, risk estimates from the Swedish MultiGenerational cohort do not generally appear to be biased by left-truncation.
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| 15. |
- Leu, Monica, 1977, et al.
(författare)
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NordicDB: A Nordic pool and portal for genome-wide control data
- 2010
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Ingår i: European Journal of Human Genetics. - 1018-4813 .- 1476-5438. ; 18:12, s. 1322-6
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Tidskriftsartikel (refereegranskat)abstract
- A cost-efficient way to increase power in a genetic association study is to pool controls from different sources. The genotyping effort can then be directed to large case series. The Nordic Control database, NordicDB, has been set up as a unique resource in the Nordic area and the data are available for authorized users through the web portal (http://www.nordicdb.org). The current version of NordicDB pools together high-density genome-wide SNP information from ∼5000 controls originating from Finnish, Swedish and Danish studies and shows country-specific allele frequencies for SNP markers. The genetic homogeneity of the samples was investigated using multidimensional scaling (MDS) analysis and pairwise allele frequency differences between the studies. The plot of the first two MDS components showed excellent resemblance to the geographical placement of the samples, with a clear NW–SE gradient. We advise researchers to assess the impact of population structure when incorporating NordicDB controls in association studies. This harmonized Nordic database presents a unique genome-wide resource for future genetic association studies in the Nordic countries.
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| 16. |
- Leu, Monica, 1977, et al.
(författare)
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“Population Lab”: The creation of virtual populations in Genetic Epidemiology Research
- 2007
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Ingår i: Epidemiology. - 1044-3983. ; 18:4, s. 433-40
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Studies of familial aggregation of disease routinely use linked population registers to construct retrospective cohorts. Although such resources have provided numerous estimates of familial risk, little is known regarding the sensitivity of the estimates to assumed disease models, changing demographics and incidence, and incompleteness of the data. Furthermore, there are no standard tools for testing the validity of estimates from standard epidemiologic designs and from new analytic strategies using register data. METHODS: We present a method and a software package for simulating realistic populations of related individuals, using easily available vital statistics (population counts and fertility and mortality rates). The virtual population is stored in a pedigree file, allowing for easy retrieval of relatives and family structures. We simulate breast cancer in our population using age-specific incidence rates. RESULTS: The Swedish population is simulated as dynamically evolving over the calendar period 1955-2002. The simulated and real population agree well on important features such as age profile, sibship size distribution, and average age at first birth. Using breast cancer as an example, we present several models of familial disease aggregation and show that the parameters used in the simulations are faithfully estimated. In addition, we illustrate how our simulated population provides insight into how incomplete family history in real register data can affect estimates of familial risk. CONCLUSIONS: This simulation method can be used to investigate various underlying models of disease aggregation in families and enhance the development of optimal approaches for family studies. The software package, Population Lab, is available for free download (http://www.meb.ki.se/ approximately marrei/software/poplab/ and http://cran.at.r-project.org/).
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| 17. |
- Leu, Monica, 1977, et al.
(författare)
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The impact of truncation and missing family links in population-based registers on familial risk estimates
- 2007
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Ingår i: American Journal of Epidemiology. - 0002-9262 .- 1476-6256. ; 166:12, s. 1461-7
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Tidskriftsartikel (refereegranskat)abstract
- Family history information is often incomplete in population-based disease registers because of truncation and/or missing family links. In this study, the authors simulated complete populations of related individuals with realistic age, family structure, and incidence rates. After mimicking the realities of register-based data, such as left truncation of family history and missing family links due to death, the authors explored recovery of familial association parameters from standard epidemiologic models. Truncation of family history produced almost no bias for a familial risk of 2 and 50 years of follow-up, but it had a dramatic impact when the familial risk was 10. The age distribution of disease and the magnitude of background incidence rates also affected family history loss and thus the magnitude of bias. One can safeguard against bias by starting follow-up later, with the number of registration years to be ignored in the analysis depending on the value of familial risk. The missing familial links due to death had no effect, except when there was differential mortality for cases with and without a family history of disease. In summary, truncation, and to a lesser extent missing family links, induces bias in familial risk estimates from population-based registers.
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| 18. |
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| 19. |
- Leu, Monica, 1977, et al.
(författare)
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Vitamin D: Epidemiology of cardiovascular risks and events
- 2011
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Ingår i: Baillière's Best Practice & Research. Clinical Endocrinology & Metabolism. - 1521-690X. ; 25:4, s. 633-46
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Forskningsöversikt (refereegranskat)abstract
- Vitamin D may influence blood pressure through the renin-angiotensin system, parathyroid hormone levels, myocardial function, inflammation, and vascular calcification. In the past several years, a number of high-quality prospective studies have examined 25(OH)vitamin D (25(OH)D) levels in relation to risk of cardiovascular disease (CVD). Studies consistently show that levels of 25(OH)D below 20–25 ng/mL are associated with an increased risk of CVD incidence or mortality. Risk appears especially elevated at 25(OH)D levels below 10 or 15 ng/mL. It is unclear if levels higher that 25 ng/mL provide further benefits for CVD disease. Currently, results from randomized clinical trials are sparse and do not allow a definitive conclusion. Given other potential benefits of vitamin D, and low potential for toxicity, deficient levels below 25–30 ng/mL should be avoided and treated when identified. Further observational and randomized clinical trial data are important to better characterize the optimal range for 25(OH)D.
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| 20. |
- Li, T. T., et al.
(författare)
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Pathogenic antibody response to glucose-6-phosphate isomerase targets a modified epitope uniquely exposed on joint cartilage
- 2023
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Ingår i: Annals of the Rheumatic Diseases. - : BMJ. - 0003-4967 .- 1468-2060. ; 82:6, s. 799-808
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Tidskriftsartikel (refereegranskat)abstract
- ObjectivesTo identify the arthritogenic B cell epitopes of glucose-6-phosphate isomerase (GPI) and their association with rheumatoid arthritis (RA). MethodsIgG response towards a library of GPI peptides in patients with early RA, pre-symptomatic individuals and population controls, as well as in mice, were tested by bead-based multiplex immunoassays and ELISA. Monoclonal IgG were generated, and the binding specificity and affinity were determined by ELISA, gel size exclusion chromatography, surface plasma resonance and X-ray crystallography. Arthritogenicity was investigated by passive transfer experiments. Antigen-specific B cells were identified by peptide tetramer staining. ResultsPeptide GPI(293-307) was the dominant B cell epitope in K/BxN and GPI-immunised mice. We could detect B cells and low levels of IgM antibodies binding the GPI(293-307) epitopes, and high affinity anti-GPI(293-307) IgG antibodies already 7 days after GPI immunisation, immediately before arthritis onset. Transfer of anti-GPI(293-307) IgG antibodies induced arthritis in mice. Moreover, anti-GPI(293-307) IgG antibodies were more frequent in individuals prior to RA onset (19%) than in controls (7.5%). GPI(293-307)-specific antibodies were associated with radiographic joint damage. Crystal structures of the Fab-peptide complex revealed that this epitope is not exposed in native GPI but requires conformational change of the protein in inflamed joint for effective recognition by anti-GPI(293-307) antibodies. ConclusionsWe have identified the major pathogenic B cell epitope of the RA-associated autoantigen GPI, at position 293-307, exposed only on structurally modified GPI on the cartilage surface. B cells to this neo-epitope escape tolerance and could potentially play a role in the pathogenesis of RA.
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| 21. |
- Nilsson, Jenny, et al.
(författare)
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Influence of Age and Sex on Disease Course and Treatment in Rheumatoid Arthritis
- 2021
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Ingår i: Open Access Rheumatology-Research and Reviews. - 1179-156X. ; 13, s. 123-138
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Tidskriftsartikel (refereegranskat)abstract
- Objective: More than 50% of patients with rheumatoid arthritis (RA) are >65 years at diagnosis. Age of onset and sex may influence the disease course, outcome and treatment. This study follows a large cohort of patients with early RA to assess contributions of age and sex to disease outcomes. Methods: Patients from the BARFOT cohort, n=2837 (68% women), were followed for eight years at predefined time points to assess inflammation, function, joint destruction and treatment with disease modifying anti-rheumatic drugs (DMARDs) and glucocorticoids (GC). The patients were divided by sex and age at inclusion (<40, 40-54, 55-69 and >= 70 years). Results: For both sexes, disease activity, function and pain improved over time, significantly more in men than in women in all age groups. In men, those <40 years displayed significantly lower DAS28 compared with all other groups. This group was also the least represented group in the study. The Sharp van der Heijde Score (SHS) increased over time in both sexes and all age groups. Women >= 70 years showed less improvement in disability and the highest progression of SHS mainly due to increased joint space narrowing. Patients <40 years were more likely to receive biological DMARDs, while those >= 70 years more often received only GC treatment. Conclusion: There were significant age- and sex-dependent differences in the medical treatment and in outcome of RA 8 years after diagnosis. The differences were most pronounced in men<40 and women >= 70 years, but whether they are due to disease phenotype or treatment is unclear.
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| 22. |
- Thorarinsdottir, Katrin, et al.
(författare)
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Cartilage destruction in early rheumatoid arthritis patients correlates with CD21−/low double-negative B cells
- 2024
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Ingår i: Arthritis Research and Therapy. - 1478-6354 .- 1478-6362. ; 26:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: Involvement of B cells in the pathogenesis of rheumatoid arthritis (RA) is supported by the presence of disease-specific autoantibodies and the efficacy of treatment directed against B cells. B cells that express low levels of or lack the B cell receptor (BCR) co-receptor CD21, CD21−/low B cells, have been linked to autoimmune diseases, including RA. In this study, we characterized the CD21+ and CD21−/low B cell subsets in newly diagnosed, early RA (eRA) patients and investigated whether any of the B cell subsets were associated with autoantibody status, disease activity and/or joint destruction. Methods: Seventy-six eRA patients and 28 age- and sex-matched healthy donors were recruited. Multiple clinical parameters were assessed, including disease activity and radiographic joint destruction. B cell subsets were analysed in peripheral blood (PB) and synovial fluid (SF) using flow cytometry. Results: Compared to healthy donors, the eRA patients displayed an elevated frequency of naïve CD21+ B cells in PB. Amongst memory B cells, eRA patients had lower frequencies of the CD21+CD27+ subsets and CD21−/low CD27+IgD+ subset. The only B cell subset found to associate with clinical factors was the CD21−/low double-negative (DN, CD27−IgD−) cell population, linked with the joint space narrowing score, i.e. cartilage destruction. Moreover, in SF from patients with established RA, the CD21−/low DN B cells were expanded and these cells expressed receptor activator of the nuclear factor κB ligand (RANKL). Conclusions: Cartilage destruction in eRA patients was associated with an expanded proportion of CD21−/low DN B cells in PB. The subset was also expanded in SF from established RA patients and expressed RANKL. Taken together, our results suggest a role for CD21−/low DN in RA pathogenesis.
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| 23. |
- Tubić, Bojan, 1984, et al.
(författare)
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Different osteocalcin forms, markers of metabolic syndrome and anthropometric measures in children within the IDEFICS cohort
- 2016
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Ingår i: Bone. - : ELSEVIER SCIENCE INC. - 8756-3282 .- 1873-2763. ; 84, s. 230-236
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Tidskriftsartikel (refereegranskat)abstract
- Objective: Osteocalcin (OC), an aboundant non-collagenous bone protein, is inversely associated with parameters of glucose metabolism. Interactions between bone tissue and energy metabolism have not been thoroughly investigated during childhood. This study investigated OC, metabolic parameters and anthropometric characteristics in normal weight and overweight/obese children. Methods: This study comprised 108 (46 normal weight/62 overweight/obese) Swedish 2-9 year old children. Anthropometric data, insulin, glucose, glycosylated haemoglobin (HbA1c), HOMA index, vitamin D, adiponectin, total OC, carboxylated OC (cOC) and undercarboxylated OC (ucOC) were analysed. Results: No difference was found for total OC between the normal and overweight/obese groups, with a mean (+/- SD) value of 82.6 ( +/- 2.8) ng/mL and 77.0 ( +/- 2.4) ng/mL, (P = 0.11), respectively. Overweight children had lower cOC levels, mean 69.1 ( +/- 2.2) ng/mL, vs. normal weight children, mean 75.6 ( +/- 2.5) ng/mL (P = 0.03). The mean ucOC levels of 7.9 ( +/- 0.4) ng/mL in overweight children did not differ vs. normal weight children, mean level 7.0 (+/- 0.4) ng/mL, (P = 0.067). None of the three OC forms correlated with any of the measured parameters. Conclusions: The cOC levels were lower in overweight children. There was no correlation between the three OC forms and any of the measured anthropometric or metabolic parameters. OC has been suggested to have a possible metabolic role, but in general the current study in prepubertal children does not support the hypothesis of an association between OC and a positive metabolic profile. (C) 2016 Elsevier Inc. All rights reserved.
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