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  • Ludvigsson, Jonas F., et al. (författare)
  • A population-based study of coeliac disease, neurodegenerative and neuroinflammatory diseases
  • 2007
  • Ingår i: Alimentary Pharmacology and Therapeutics. - 0269-2813 .- 1365-2036. ; 25:11, s. 1317-1327
  • Tidskriftsartikel (refereegranskat)abstract
    • Background It has been suggested that coeliac disease (CD) is associated with several neurological diseases. However, the evidence of such an association is inconclusive as earlier research has often been based on small numbers with retrospective data collection. Aim To use Cox regression to examine the risk of neurological disease in individuals with CD. Methods Through Swedish national registers we identified some 14 000 individuals with a diagnosis of CD (1964–2003) and 70 000 reference individuals matched for age, sex, calendar year and county. Results Coeliac disease was associated with later polyneuropathy [hazard ratio (HR) = 3.4; 95% CI = 2.3–5.1]. We found no statistically significant association between CD and subsequent multiple sclerosis (HR = 0.9; 95% CI = 0.3–2.3), Parkinson’s disease (HR = 1.2; 95% CI = 0.8–1.9), Alzheimer’s disease (HR = 1.5; 95% CI = 0.9–2.6), hereditary ataxia (HR = 1.3; 95% CI = 0.5–3.6), the symptom ataxia (HR = 1.9; 95% CI = 0.6–6.2), Huntington’s disease (HR = 1.7; 95% CI = 0.3–8.6), myasthenia gravis (HR = 0.8; 95% CI = 0.2–3.8) or spinal muscular atrophy (HR = 0.5; 95% CI = 0.1–3.8). Prior polyneuropathy was associated with subsequent CD (odds ratio = 5.4; 95% CI = 3.6–8.2). Conclusions The association between CD and polyneuropathy indicates shared risks. We suggest that individuals with polyneuropathy routinely undergo screening for CD. There is no notable association between CD and other neurological outcomes investigated in this study.
  • Ludvigsson, Jonas F., et al. (författare)
  • Coeliac disease and the risk of fractures : a general population-based cohort study
  • 2007
  • Ingår i: Alimentary Pharmacology and Therapeutics. - Oxford : Blackwell Scientific. - 0269-2813 .- 1365-2036. ; 25:3, s. 273-285
  • Tidskriftsartikel (övrigt vetenskapligt)abstract
    • Background: Earlier studies have suggested that untreated coeliac disease may be associated with osteoporosis, but results are contradictory for the risk of long-term fractures.Aim: To study the association between coeliac disease and fractures.Methods: We used Cox regresson to examine the future risk of hip fracture and fracture of any type in more than 13 000 individuals with coeliac disease and 65 000 age- and sex-matched reference individuals in a general population-based cohort.Results: During follow-up, 1365 first hip fractures and 4847 fractures of any type occurred. Coeliac disease was positively associated with subsequent hip fracture (hazard ratio = 2.1; 95% CI = 1.8-2.4) (in children: hazard ratio = 2.6; 95% CI = 1.1-6.2) and fractures of any type (hazard ratio = 1.4; 95% CI = 1.3-1.5) (in children: hazard ratio = 1.1; 95% CI = 1.0-1.2). The absolute excess risk of hip fractures in children with coeliac disease was 4/100 000 person-years. Incidence ratios for hip fracture in individuals with CD were around two both prior to diagnosis of coeliac disease and afterwards; this risk increase remained 20 years after diagnosis of coeliac disease.Conclusions: Individuals with coeliac disease, including children with coeliac disease, may be at increased risk of hip fracture and fracture of any type. Coeliac disease may be positively associated with long-term hip fracture risk.
  • Rydén, Petra, 1972-, et al. (författare)
  • What happens with the healthiness of the diet among Swedish adolescent  boys and girls when a gluten-free diet is required?
  • Annan publikation (övrigt vetenskapligt)abstract
    • Objectives To explore how diagnosis of celiac disease (CD) in early adolescence affects overall food intake and healthiness of the diet in comparison with age- and sex matched controls and children with CD diagnosed in early childhood. Methods This is a longitudinal dietary sub-study of a school-based CD-screening of 12-year-olds (ETICS - Exploring the Iceberg of Coeliacs in Sweden), a part of the PreventCD project. The dietary study was conducted in 2005-2008 and included the following groups resulting from the screening: I) screening-detected CD cases (n=80), II) previously diagnosed CD cases (n=28), and III) two samples of age- and sex matched non-CD children (admission, n=619; follow-up, n=447). All CD cases completed two food-frequency-and-amount-questionnaires (FFQ), covering the previous four weeks; one at admission and one at a follow-up 18-24 months later. The screening-detected CD cases completed the first FFQ before a gluten free diet was initiated. The non-CD children consisted of a cross-sectional sample at each time point, and thus only completed one FFQ each (i.e. either at admission or follow-up). The Goldberg cut-off method was used to validate reported energy intake. The food choices at admission and follow-up were compared among the three groups, and the healthiness of the diet evaluated using two Swedish dietary indexes. Results and Conclusion Intakes of most food groups were similar at baseline. The adolescents diagnosed with CD did only minor changes in their overall food choices. Visible changes were reductions within food groups where gluten-free alternatives are not readily available, such as pastries and pizza. In contrast, total intake of bread and pasta did not change. All three groups scored fairly low on the dietary indexes at both time points, and there is an obvious need to improve the healthiness of the adolescent diet, whether CD is present or not.
  • Jonsson, Åsa, 1969- (författare)
  • How to create and analyze a Heart Failure Registry with emphasis on Anemia and Quality of Life
  • 2017
  • Doktorsavhandling (övrigt vetenskapligt)abstract
    • Background and aimsHeart failure (HF) is a major cause of serious morbidity and death in the population and one of the leading medical causes of hospitalization among people older than 60 years. The aim of this thesis was to describe how to create and how to analyze a Heart Failure Registry with emphasis on Anemia and Quality of Life. (Paper I) We described the creation of the Swedish Heart Failure Registry (SwedeHF) as an instrument, which may help to optimize the handling of HF patients and show how the registry can be used to improve the management of patients with HF. (Paper II) In order to show how to analyze a HF registry we investigated the prevalence of anemia, its predictors, and its association with mortality and morbidity in a large cohort of unselected patients with HFrEF included in the SwedeHF, and to explore if there are subgroups of HF patients identifying high--‐risk patients in need of treatment. (Paper III) In order to show another way of analyzing a HF registry we assessed the prevalence of, associations with, and prognostic impact of anemia in patients with HFmrEF and HFpEF. (Paper IV) Finally we examined the usefulness of EQ--‐ 5D as a measure of patient--‐reported outcomes among HF patients using different analytical models and data from the SwedeHF, and comparing results about HRQoL for patients with HFpEF and HFrEF.Methods An observational study based on the SwedeHF database, consisting of about 70 variables, was undertaken to describe how a registry is created and can be used (Paper I). One comorbidity (anemia) was applied to different types of HF patients, HFrEF (EF <40%) (II) and HFmrEF (EF 40--‐49% ) or HFpEF (> 50%) (III) analyzing the data with different statistical methods. The usefulness of EQ--‐5D as measure of patient--‐ reported outcomes was studied and the results about HRQoL were compared for patients with HFpEF and HFrEF (IV).ResultsIn the first paper (Paper I) we showed how to create a HF registry and presented some characteristics of the patients included, however not adjusted since this was not the purpose of the study. In the second paper (Paper II) we studied anemia in patients with HFrEF and found that the prevalence of anemia in HFrEF were 34 % and the most important independent predictors were higher age, male gender and renal dysfunction. One--‐year survival was 75 % with anemia vs. 81 % without (p<0,001). In the matched cohort after propensity score the hazard ratio associated with anemia was for all--‐cause death 1.34. Anemia was associated with greater risk with lower age, male gender, EF 30--‐39%, and NYHA--‐class I--‐II. In the third paper (Paper III) we studied anemia in other types of HF patients and found that the prevalence in the overall cohort in patients with EF > 40% was 42 %, in HFmrEF 38 % and in HFpEF (45%). Independent associations with anemia were HFpEF, male sex, higher age, worse New York Heart Association class and renal function, systolic blood pressure <100 mmHg, heart rate ≥70 bpm, diabetes, and absence of atrial fibrillation. One--‐year survival with vs. without anemia was 74% vs. 89% in HFmrEF and 71% vs. 84% in HFpEF (p<0.001 for all). Thus very similar results in paper II and III but in different types of HF patients. In the fourth paper (Paper IV) we studied the usefulness of EQ--‐5D in two groups of patients with HF (HFpEF and HFrEF)) and found that the mean EQ--‐5D index showed small reductions in both groups at follow--‐up. The patients in the HFpEF group reported worsening in all five dimensions, while those in the HFrEF group reported worsening in only three. The Paretian classification showed that 24% of the patients in the HFpEF group and 34% of those in the HFrEF group reported overall improvement while 43% and 39% reported overall worsening. Multiple logistic regressions showed that treatment in a cardiology clinic affected outcome in the HFrEF group but not in the HFpEF group (Paper IV).Conclusions The SwedeHF is a valuable tool for improving the management of patients with HF, since it enables participating centers to focus on their own potential for improving diagnoses and medical treatment, through the online reports (Paper I). Anemia is associated with higher age, male gender and renal dysfunction and increased risk of mortality and morbidity (II, III). The influence of anemia on mortality was significantly greater in younger patients in men and in those with more stable HF (Paper II, III). The usefulness of EQ--‐5D is dependent on the analytical method used. While the index showed minor differences between groups, analyses of specific dimensions showed different patterns of change in the two groups of patients (HFpEF and HFrEF). The Paretian classification identified subgroups that improved or worsened, and can therefore help to identify needs for improvement in health services (Paper IV).
  • Ludvigsson, Jonas F., et al. (författare)
  • Coeliac disease and risk of mood disorders : a general population-based cohort study
  • 2007
  • Ingår i: Journal of Affective Disorders. - Amsterdam : Elsevier Biomedical. - 0165-0327 .- 1573-2517. ; 99:1, s. 117-126
  • Tidskriftsartikel (övrigt vetenskapligt)abstract
    • Background Earlier research has indicated a positive association between coeliac disease (CD) and some mental disorders. Studies on CD and depression have inconsistent findings and we know of no study of CD and the risk of bipolar disorder (BD). Methods We used Cox regression to investigate the risk of subsequent mood disorders (MD); depression and BD in 13,776 individuals with CD and 66,815 age- and sex-matched reference individuals in a general population-based cohort study in Sweden. We also studied the association between prior MD and CD through conditional logistic regression. Results CD was associated with an increased risk of subsequent depression (Hazard ratio (HR)=1.8; 95% CI=1.6–2.2; p<0.001, based on 181 positive events in individuals with CD and 529 positive events in reference individuals). CD was not associated with subsequent BD (HR=1.1; 95% CI=0.7–1.7; p=0.779, based on 22 and 99 positive events). Individuals with prior depression (OR=2.3; 95% CI=2.0–2.8; p<0.001) or prior BD (OR=1.7; 95% CI=1.2–2.3; p=0.001) were at increased risk of a subsequent diagnosis of CD. Limitations Study participants with CD and MD may have more severe disease than the average patient with these disorders since they were identified through a hospital-based register. Conclusions CD is positively associated with subsequent depression. The risk increase for CD in individuals with prior depression and BD may be due to screening for CD among those with MD.
  • Elfström, Peter, 1974-, et al. (författare)
  • Hematopoietic cancer including lymphoma in celiac disease according to Marsh criteria 0-3
  • Annan publikation (övrigt vetenskapligt)abstract
    • Background: Celiac disease (CD) is associated with an increased risk of lymphoma, but it is unknown if borderline mucosal damage and latent CD are risk factors for lymphoma.Methods: We examined the risk of hematopoietic cancer in a nationwide population–based cohort of 28,800 individuals with biopsy-verified CD (villous atrophy, Marsh 3), 12,663 individuals with small intestinal inflammation (Marsh 1+2), and 3,551 with latent CD (positive antiendomysial, tissue transglutaminase or antigliadin test but normal mucosa on biopsy). The study participants were identified through all pathology departments (n=28) in Sweden and were biopsied in 1969-2006 (median: 1998). Cox regression estimated the hazard ratio (HR) for hematopoietic malignancies.Results: While biopsy-verified CD and intestinal inflammation were both statistically significantly associated with lymphoma (CD: HR = 3.18; 95% CI = 2.63-3.83; inflammation: 1.66; 1.28-2.17), latent CD was not (1.04; 0.44-2.43). CD was associated with both non-Hodgkin’s (NHL) and Hodgkin’s lymphoma (HL) (4.81; 3.81-6.07 and 4.39; 2.59-7.45 respectively). Risk estimates for NHL and HL were lower in inflammation (1.65; 1.15-2.38 and 1.48; 0.60-3.62 respectively) and latent CD (1.79; 0.74-4.34 and 1.08; 0.13-9.00 respectively). No increased risk of lymphoma was seen in children with a small intestinal biopsy. This study found no association between leukemia and small intestinal pathology.Conclusion: CD is associated with an increased risk of lymphoma. This risk increase was also seen in individuals with small intestinal inflammation. Latent CD is not associated with lymphoma of any kind, and positive CD serology alone cannot be used to predict future risk of lymphoma.
  • Hjortswang, Henrik, et al. (författare)
  • Defining Clinical Criteria for Clinical Remission and Disease Activity in Collagenous Colitis
  • 2009
  • Ingår i: Inflammatory Bowel Diseases. - : Oxford University Press. - 1536-4844 .- 1078-0998. ; 15:12, s. 1875-1881
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Collagenous colitis is a chronic inflammatory bowel disease accompanied mainly by nonbloody diarrhea. The objectives of treatment are to alleviate the symptoms and minimize the deleterious effects on health-related quality of life (HRQOL). There is still no generally accepted clinical definition of remission or relapse. The purpose of this study was to analyze the impact of bowel symptoms on HRQOL and accordingly suggest criteria for remission and disease activity based on impact of patient symptoms on HRQOL. Methods: The design was a cross-sectional postal survey of 116 patients with collagenous colitis. The main outcome measures were 4 HRQOL questionnaires: the Short Health Scale, the Inflammatory Bowel Disease Questionnaire, the Rating Form of IBD Patient Concerns, and the Psychological General Well-Being Index, and a 1-week symptom diary recording number of stools/day and number of watery stools/day. Results: Severity of bowel symptoms had a deleterious impact on patients' HRQOL. Patients with a mean of >= 3 stools/day or a mean of >= 1 watery stool/day had a significantly impaired HRQOL compared to those with <3 stools/day and < 1 watery stool/day. Conclusions: We propose that clinical remission in collagenous colitis is defined as a mean of <3 stools/day and a mean of < 1 watery stool per clay and disease activity to be a daily mean of >= 3 stools or a mean of >= 1 watery stool.
  • Ludvigsson, Jonas F., et al. (författare)
  • Effect of HLA DQ2, dietary exposure and coeliac disease on the development of antibody response to gliadin in children
  • 2006
  • Ingår i: Scandinavian Journal of Gastroenterology. - 0036-5521 .- 1502-7708. ; 41:8, s. 919-928
  • Tidskriftsartikel (refereegranskat)abstract
    • OBJECTIVE: To study the effect of HLA DQ2, dietary history and development of coeliac disease (CD) on the induction of antibody response to wheat gliadin and cow's milk, beta-lactoglobulin between 1 and 2.5 years of age in children who developed CD and in healthy children. MATERIAL AND METHODS: Infants participating in a birth cohort study (the ABIS study) in Sweden were studied. Thirty-nine children developed CD (=cases), confirmed through biopsy, during follow-up until 2.5-5 years of age. A total of 181 healthy control children were matched for duration of exclusive breast-feeding, birth-weight, gender, maternal smoking and season of birth. IgG and IgA antigliadin and anti-beta-lactoglobulin antibodies were measured using enzyme immunoassay (EIA). The effects of HLA-risk genotypes, DQ2 and DQ8, on CD were also considered. RESULTS: Children who developed CD had higher IgG and IgA antigliadin and anti-beta-lactoglobulin antibody levels at 1 year of age than controls (all comparisons: p<0.001). Similar differences were seen between cases with as yet undiagnosed CD by 1 year of age and controls, and also when cases were compared with HLA-matched controls. Higher levels of IgG and IgA antibodies to beta-lactoglobulin (p=0.003; p=0.001), but not to gliadin, were found in treated cases versus controls at 2.5 years of age. HLA-DQ2-positive healthy children had lower levels of IgG and IgA antigliadin antibodies than HLA-DQ2 negative controls at 1 year of age (p=0.004; p=0.012). CONCLUSIONS: Enhanced humoral response emerging not only to gliadin, but also to other food antigens seems to be primarily associated with CD. Poor induction of antibody response to wheat gliadin in healthy children with the HLA-DQ2 risk molecule could at least partly explain the genetic predisposition to gluten intolerance and CD.
  • Hjortswang, Henrik, et al. (författare)
  • The Short Health Scale : a valid measure of subjective health in ulcerative colitis
  • 2006
  • Ingår i: Scandinavian Journal of Gastroenterology. - Oslo : Taylor & Francis. - 0036-5521 .- 1502-7708. ; 41:10, s. 1196-1203
  • Tidskriftsartikel (refereegranskat)abstract
    • OBJECTIVE: Assessment of health-related quality of life (HRQOL) is important in both clinical practice and clinical trials, and several multi-item questionnaires are currently in use. We have devised and evaluated a simplified four-item questionnaire, the Short Health Scale (SHS), representing each of four health dimensions: (a) symptom burden, (b) social function, (c) disease-related worry and (d) general well-being. MATERIAL AND METHODS: Three hundred patients with ulcerative colitis completed the SHS and three other HRQOL questionnaires (IBDQ, RFIPC and PGWB). Half of the patients repeated the questionnaires after 6 months - or earlier if disease activity changed. Test-retest reliability was derived from measurements of the SHS questions, 2 weeks apart, on 18 patients in remission. RESULTS: Patients in relapse scored higher on each of the four SHS questions than patients in remission (p < 0.001). Each of the four SHS scores were associated with results of their corresponding health dimension obtained with the other three questionnaires (rs=0.57-0.78, p < 0.001) (validity). The results of the SHS proved stable on repeated measurement with a 2-week interval in patients in remission (rs=0.71-0.91, p < 0.01) (test-retest reliability). Patients with a change in disease activity had a significant change in their SHS scores (p < 0.05) (responsiveness). CONCLUSIONS: The SHS is a valid, reliable and responsive measure of subjective health in patients with ulcerative colitis. It is simple to administer, quickly completed and the results do not need further calculations. The SHS can be used in clinical trials and in clinical practice to identify the patient's main problems affecting health.
  • Stjernman, Henrik, et al. (författare)
  • Evaluation of the inflammatory bowel disease questionnaire in Swedish patients with Crohn's disease
  • 2006
  • Ingår i: Scandinavian Journal of Gastroenterology. - 0036-5521 .- 1502-7708. ; 41:8, s. 934-943
  • Tidskriftsartikel (refereegranskat)abstract
    • OBJECTIVE: Health-related quality of life (HRQoL) is an important measure of inflammatory bowel disease (IBD) health outcome. The Inflammatory Bowel Disease Questionnaire (IBDQ) comprising 32 items grouped into four dimensions is a widely used IBD-specific HRQoL instrument. The purpose of this study was to evaluate the validity, reliability and responsiveness of the Swedish translation of the IBDQ in patients with Crohn's disease (CD). MATERIAL AND METHODS: Four hundred and forty-eight patients with CD completed the IBDQ and three other HRQoL questionnaires (Rating Form of IBD Patient Concerns; Short Form-36; and the Psychological General Well-Being Index) in connection with their regular visit at the outpatient clinic. Disease activity was assessed by the physician on a 4-point Likert scale. Thirty-two patients who were stable in remission completed the questionnaires a second time, 4 weeks later. A total of 418 patients repeated all measurements after 6 months. RESULTS: The dimensional scores were highly correlated with other measures of corresponding aspects of HRQoL and were significantly better in remission than in relapse. High test-retest correlations indicated good reliability. Responsiveness was confirmed in patients whose disease activity changed over time. However, high correlations between the dimensions, poor correlations between items within each dimension, and factor analysis all indicated that the original grouping of the items is not valid for Swedish CD patients. CONCLUSIONS: Although the Swedish IBDQ has good external validity, reliability and responsiveness for patients with CD, our results did not support the original grouping of the items.
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