| 1. |
- Röckert Tjernberg, Anna, 1975-
(författare)
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Celiac disease and Infections
- 2019
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Background: Celiac disease (CD) is a chronic immune-mediated enteropathy affecting about 1% of the population worldwide. CD is triggered by ingestion of gluten in genetically predisposed individuals but additional factors (e.g. infections) are required for the disease to develop. CD also seems to be associated with infectious complications.Aim: The main objective of this thesis was to increase the knowledge about the associations between CD and infections.Methods: Epidemiological and laboratory approaches. Studies I-III used a data set consisting of small intestinal biopsy reports. The biopsies were taken in 1969-2008 and collected in 2006-2008. A total of 29,096 individuals with CD, 13,306 with inflammation and 3,719 with potential CD were identified. Each individual was matched with up to 5 controls from the general population (n= 228,632). Through linkage of the data to the Patient Register study I examined the risk of hospital visits due to respiratory syncytial virus (RSV) in children <2 years prior to onset of CD. Study II used the Patient Register and Cause of Death Register to assess whether CD affects the outcome in sepsis. Study III linked the data to microbiological data bases and the Public Health Agency to estimate risk of invasive pneumococcal disease (IPD) in CD. In study IV children with CD and controls were recruited from Kalmar County Hospital. Complement activation (C3a and sC5b-9) in plasma were analysed after incubation with pneumococci.Results: Study I found that children with CD were more likely than controls to have attended hospital due to RSV infection prior to diagnosis (odds ratio 1.46; 95% confidence interval (CI)=1.02-2.07). CD did not seem to influence survival in sepsis (adjusted hazard ratio (HR) 1.10 95%CI=0.72-1.69) (study II). Study III indicated a 46% risk increase for individuals with CD to acquire IPD (HR 1.46; 95%CI=1.05-2.03) but study IV did not reveal any differences in complement response in regard to CD status (p=0.497and p=0.724), explaining this excess risk.Conclusion: This thesis supports associations between CD and infections preceding and complicating diagnosis. However, CD does not seem to influence the outcome in a severe infection like sepsis and altered complement function is unlikely to be responsible for the excess IPD risk in CD.
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| 2. |
- Sundelin, Heléne E.K. 1965-
(författare)
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Comorbidity and complications in neurological diseases
- 2017
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Background: Neurological diseases are complex and many share etiology as well as comorbidities. Epilepsy, a brain disorder characterized by an enduring predisposition to generate epileptic seizures and autism spectrum disorder (ASD), are considered to be associated, but the connection is still not fully uncovered. Cerebral palsy (CP), a lifelong, nonspecific, non-progressive disorder of posture and movement control, and Ehlers-Danlos Syndrome (EDS), a connective tissue disorder, both have many consequences for health and wellbeing throughout life.Aims: The aim of this thesis was to explore the impact of comorbidity and complications in neurological diseases and EDS. The objective was to gain information on the nature of the connection between epilepsy and ASD, if EDS, ASD and CP have consequences for pregnancy outcome, and the risk of traffic accidents in individuals with epilepsy.Materials and methods: The studies are all historical observational population- based cohort studies with prospectively collected data from national registers. The risk of ASD was analysed in 85,201 individuals with epilepsy and compared with 425,760 controls as well as for their firstdegree relatives. In a cohort of 1,248,178 singleton births, 314 births to women with EDS, 2,072 births to women with ASD, and 770 births to women with CP, pregnancy outcome was explored. The risk of traffic accidents was estimated in 29,220 individuals with epilepsy and 267,637 matched controls.Results: There is an increased risk of; ASD in individuals with epilepsy and their relatives, moderately preterm birth and pre-eclampsia in maternal ASD, of preterm birth in maternal CP and transport accidents in individuals with epilepsy. There is no increased risk of adverse pregnancy outcome in women with EDS.Conclusions: This thesis found proofs of a bidirectional association between epilepsy and ASD, that ASD and CP have consequences for pregnancy outcome and epilepsy is a risk factor for traffic accidents.
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| 3. |
- Bozorg, Soran Rabin, 1993-
(författare)
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Various Aspects of Gastrointestinal Disease : Examining Validity and Health Economic Outcomes
- 2022
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Licentiatavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Introduction: Recent years have seen significant research advances within the gastroenterological field. Some of these consist of the recognition of serrated polyps as a precursor to colorectal cancer, and the realization of the health economic burden associated with gastrointestinal diseases.Aim: In this thesis, we aim to validate the specificity of serrated polyps in the ESPRESSO cohort (Paper I). We also aim to estimate work loss in patients with celiac disease, including the temporal relationship of work loss before and after diagnosis (Paper II).Method: By using the ESPRESSO cohort, we collected data on patients with serrated polyps and patients with celiac disease. In Paper I, the specificity of serrated polyps in the ESPRESSO cohort were validated by a structured retrospective review of patient chart. In Paper II, we estimated work loss in patients with celiac disease as compared withgeneral-population comparators matched on age, sex, county of residence and year of diagnosis.Result: The presence of a serrated polyp was confirmed in 101 out of 106 individuals identified through the ESPRESSO cohort, yielding a positive predictive value of 95% (95% confidence interval: 89-98%). Patients with celiac disase had 42.5 lost work days as compared to 28.6 days in comparators (mean difference, 14.7; 95% confidence interval, 13.2-16.2), corresponding to a relative increase of 49%. Excess work loss in patients with celiac disease was observed even 5 years before diagnosis and remained eleveated during the years after diagnosis this loss. Notebly, the excess work loss was concentrated to a small proportion while most celiac patients did not have any work loss before or after diagnosis. Conclusion: The ESPRESSO cohort has a high specificity for serrated polyps. Patients with celiac disease miss more work days than the general population even before diagnosis, and this loss persists after diagnosis.
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| 4. |
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| 5. |
- Karlqvist, Sara, 1992-, et al.
(författare)
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Comparative risk of serious infection with vedolizumab vs anti-TNF in Inflammatory Bowel Disease : Results from nationwide Swedish registers
- 2024
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Ingår i: Journal of Crohn's & Colitis. - : Oxford University Press. - 1873-9946 .- 1876-4479. ; 18:Suppl. 1, s. I1291-I1293
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Background: The real-world comparative safety of vedolizumab in inflammatory bowel disease (IBD) remains uncertain. We aimed to assess the risk of serious infection in IBD patients treated with vedolizumab, compared to (i) those treated with anti-tumour necrosis factor (TNF) treatment and (ii) the general population.Methods: In this nationwide cohort study, treatment episodes were identified from Swedish health registers (from 1 May 2014 – 31 December 2020). Patients were considered exposed from initiation of treatment until 90 days after discontinuation of treatment. We used Cox regression with propensity score-matched cohorts to estimate hazard ratios (HRs) for incident serious infection, defined as infection requiring hospital admission.Results: After propensity score matching, the cohorts were not materially different at baseline with regard to demographic, disease and treatment characteristics (Table 1). During 1376 treatment-episodes in patients with Crohn’s disease, there were 5.18 (95%CI: 3.98-6.63) serious infections per 100 person-years (PY) with vedolizumab vs 3.54 (95%CI: 2.50-4.85) per 100 PY with anti-TNF; HR 1.72 (95%CI: 1.12-2.65; Figure 1A). When examining site-specific infections in Crohn’s disease, vedolizumab was associated with an HR of 2.47 (95% CI: 0.96-6.39) for serious gastrointestinal infections. Compared to the rate of 0.75 (95%CI: 0.59-0.92) serious infections per 100 PY in the general population, vedolizumab demonstrated an increased HR of 7.00 (95%CI: 5.04-9.72).Across 1294 episodes among patients with ulcerative colitis there were 3.74 (95%CI: 2.66-5.11) serious infections per 100 PY with vedolizumab vs 3.42 (95%CI: 2.31-4.89) per 100 PY with anti-TNF, corresponding to HRs of 0.80 (95%CI: 0.47-1.36, Figure 1B) within the initial 1.1 years of treatment and 2.03 (95%CI: 0.65-6.32) after 1.1 years (follow-up truncated due to non-proportional hazards). In ulcerative colitis, there was no statistically significant association between vedolizumab treatment and any of the site-specific serious infections. Compared to the rate of 0.69 (95%CI: 0.53-0.87) serious infections per 100 PY in the general population, vedolizumab showed an increased HR of 5.45 (95%CI: 3.67-8.11).Conclusion: Vedolizumab was associated with higher hazard ratios of serious infections compared to anti-TNF in Crohn’s disease, but not in ulcerative colitis. Nonetheless, in both IBD subtypes vedolizumab exhibited increased hazard ratios compared to the general population. These results underscore the importance of heightened clinical awareness of infections in vedolizumab-treated patients and may help clinicians understanding the optimal positioning of vedolizumab.
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| 6. |
- Röjler, Lovisa, 1983-
(författare)
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Eosinophilic esophagitis and disease complications : register-based studies
- 2023
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- This thesis presents four studies on Eosinophilic Esophagitis (EoE). The overall aim is to grasp the basics of epidemiologic research and use this understanding on EoE disease complications. EoE is a fairly new inflammatory disease with clinicopathological diagnosis that increases in prevalence. It is considered a relatively mild disease, but the evidence concerning mortality and morbidity is scarce. Although EoE has a prevalence peak in childbearing age, pregnancy outcomes are poorly examined. In Study I, a random portion of 131 patient charts from the cohort werecollected for a diagnosis validation through a patient chart review. EoE was found in 99 patients, which corresponds to a positive predictive value of 89%. The cohort was predominately male, and the most common symptom was dysphagia. Study II examines mortality in EoE individuals compared to matched reference individuals using survival analysis. We performed sibling analysis to adjust for intrafamilial (genetic and environmental) confounding. We found no elevated risk for death. Study III uses a similar method to find higher risk of psychiatric comorbidity among EoE patients compared to matched reference individuals. Mean follow-up time was 4.03 years, and there were 106 events of psychiatric disease in the EoE-group, which corresponds to an elevated risk of 50% compared to reference individuals. Study IV investigates outcomes of pregnancy in EoE females versus comparators. The main outcome is premature birth; in secondary analyses, we examined both maternal and fetal outcomes. The only elevated risk was low birth weight; although a significant finding, it was still based on a small sample size and should be interpreted with caution.
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| 7. |
- Sun, Jiangwei, et al.
(författare)
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Long-term risk of arrhythmias in patients with inflammatory bowel disease : A population-based, sibling-controlled cohort study
- 2023
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Ingår i: PLoS Medicine. - : Public Library of Science (PLoS). - 1549-1277 .- 1549-1676. ; 20:10
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundAlthough previous evidence has suggested an increased risk of cardiovascular disease (CVD) in patients with inflammatory bowel disease (IBD), its association with arrhythmias is inconclusive. In this study, we aimed to explore the long-term risk of arrhythmias in patients with IBD.Methods and findingsThrough a nationwide histopathology cohort, we identified patients with biopsy-confirmed IBD in Sweden during 1969 to 2017, including Crohn's disease (CD: n = 24,954; median age at diagnosis: 38.4 years; female: 52.2%), ulcerative colitis (UC: n = 46,856; 42.1 years; 46.3%), and IBD-unclassified (IBD-U: n = 12,067; 43.8 years; 49.6%), as well as their matched reference individuals and IBD-free full siblings. Outcomes included overall and specific arrhythmias (e.g., atrial fibrillation/flutter, bradyarrhythmias, other supraventricular arrhythmias, and ventricular arrhythmias/cardiac arrest). Flexible parametric survival models estimated hazard ratios (aHR) with 95% confidence intervals (95% CIs), after adjustment for birth year, sex, county of residence, calendar year, country of birth, educational attainment, number of healthcare visits, and cardiovascular-related comorbidities. Over a median of approximately 10 years of follow-up, 1,904 (7.6%) patients with CD, 4,154 (8.9%) patients with UC, and 990 (8.2%) patients with IBD-U developed arrhythmias, compared with 6.7%, 7.5%, and 6.0% in reference individuals, respectively. Compared with reference individuals, overall arrhythmias were increased in patients with CD [54.6 versus 46.1 per 10,000 person-years; aHR = 1.15 (95% CI [1.09, 1.21], P < 0.001)], patients with UC [64.7 versus 53.3 per 10,000 person-years; aHR = 1.14 (95% CI [1.10, 1.18], P < 0.001)], and patients with IBD-U [78.1 versus 53.5 per 10,000 person-years; aHR = 1.30 (95% CI [1.20, 1.41], P < 0.001)]. The increased risk persisted 25 years after diagnosis, corresponding to 1 extra arrhythmia case per 80 CD, 58 UC, and 29 IBD-U cases over the same period. Patients with IBD also had a significantly increased risk of specific arrhythmias, except for bradyarrhythmias. Sibling comparison analyses confirmed the main findings. Study limitations include lack of clinical data to define IBD activity, not considering the potential role of IBD medications and disease activity, and the potential residual confounding from unmeasured factors for arrhythmias.ConclusionsIn this study, we observed that patients with IBD were at an increased risk of developing arrhythmias. The excess risk persisted even 25 years after IBD diagnosis. Our findings indicate a need for awareness of this excess risk among healthcare professionals.
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| 8. |
- Visuri, Isabella, 1991-, et al.
(författare)
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Predictors of drug survival : A cohort study comparing anti-tumour necrosis factor agents using the Swedish inflammatory bowel disease quality register
- 2021
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Ingår i: Alimentary Pharmacology and Therapeutics. - : Blackwell Science Ltd.. - 0269-2813 .- 1365-2036. ; 54:7, s. 931-943
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Tidskriftsartikel (refereegranskat)abstract
- Background: Whether long-term effectiveness differs between anti-tumour necrosis factor (anti-TNF) agents is unknown.Aims: To examine drug survival of first-line anti-TNF agents and identify predictors of discontinuation. To reduce channelling bias, we also compared drug survival of the second anti-TNF.Methods: Biologic-naive patients (N = 955) recorded in the Swedish IBD Quality Register (SWIBREG) were examined. We used propensity score matching, comparing drug survival over up to three years of follow-up. Cox regression estimated adjusted hazard ratios (aHRs) with 95% confidence intervals (CIs).Results: In Crohn's disease, discontinuation because of lack/loss of response was 32% [95%CI = 26%-38%] for infliximab versus 16% [95%CI = 11%-21%] for adalimumab. Infliximab [vs adalimumab; aHR = 1.96; 95%CI = 1.20-3.21] and colonic disease (L2) [vs no L2; aHR = 2.17; 95% CI = 1.26-3.75] were associated with higher discontinuation rates, whereas normalised CRP at three months [aHR = 0.40; 95% CI = 0.19-0.81] with a lower rate. Consistently, patients who switched from adalimumab to infliximab (vs infliximab to adalimumab) had earlier discontinuation (P = 0.04). Concomitant use of immunomodulators was associated with a lower adverse drug reaction-mediated discontinuation rate [aHR = 0.46; 95% CI = 0.28-0.77], in part explained by fewer infusion reactions [aHR = 0.27; 95% CI = 0.08-0.89]. In ulcerative colitis, the probability of discontinuation because of lack/loss of response was 40% [95% CI = 33%-47%] for infliximab versus 37% [95% CI = 21%-53%] for adalimumab. Disease duration >= 10 years [aHR = 0.25; 95% CI = 0.10-0.58] and normalised CRP after three months [aHR = 0.39; 95% CI = 0.18-0.84] were associated with lower discontinuation rates.Conclusions: Clinical characterisation of patients may aid decision-making on anti-TNF treatment. The consistently shorter drug survival for infliximab (vs adalimumab) in Crohn's disease, suggests a potential difference between the two drugs.
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| 9. |
- Jarrick, Simon, 1977-, et al.
(författare)
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Immunoglobulin A nephropathy and ischemic heart disease : a nationwide population-based cohort study
- 2021
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Ingår i: BMC Nephrology. - : BioMed Central (BMC). - 1471-2369. ; 22:1
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Chronic kidney disease has been linked to cardiovascular disease and specifically ischemic heart disease (IHD), but large-scale population data in patients with immunoglobulin A nephropathy (IgAN) are missing.OBJECTIVE: To examine absolute and relative risks for IHD in patients with IgAN.METHODS: Population-based register-based cohort study in Sweden. We identified 3945 patients with biopsy-verified IgAN, and 19,272 age- and sex-matched reference individuals from the general population. To reduce residual confounding from genetic factors and early environmental factors we carried out secondary analyses, where we compared 3039 IgAN patients with 6729 siblings, whereas a spousal analysis consisted of 2377 married couples where one of the spouses had IgAN. Data on IHD and end-stage renal disease (ESRD) were retrieved from the nationwide Patient Register. Cox regression estimated hazard ratios (HRs) adjusted for matching variables, education, country of birth, cancer, diabetes mellitus, and other systemic inflammatory diseases.RESULTS: During a follow-up of 55,527 person-years (py; mean follow-up 14.1 years), 371 patients (9.4%) with IgAN developed IHD (6.7/1000 py), compared with 1070 (5.6%) in 287,677 py in reference individuals (3.7/1000 py). The corresponding adjusted HR was 1.86 (95%CI = 1.63-2.13), equivalent to one extra case of IHD per 34 IgAN patients followed-up for 10 years. HRs were similar in men and women with IgAN, but higher in the first year after diagnosis and in patients born outside the Nordic countries. Patients with IgAN were at increased risk of IHD also compared to siblings (HR = 2.07; 95%CI = 1.62-2-64) and spouses (HR = 1.91; 95%CI = 1.40-2.61).CONCLUSIONS: In this nationwide population-based study, patients with IgAN were at an 86% increased risk of future IHD.
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| 10. |
- Laszkowska, M., et al.
(författare)
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Systematic review with meta-analysis : the prevalence of coeliac disease in patients with osteoporosis
- 2018
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Ingår i: Alimentary Pharmacology and Therapeutics. - : Blackwell Publishing. - 0269-2813 .- 1365-2036. ; 48:6, s. 590-597
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Forskningsöversikt (refereegranskat)abstract
- Background: Earlier studies have produced highly varying risk estimates for the prevalence of coeliac disease (CD) in osteoporosis.Aims: To investigate the prevalence of CD among individuals with osteoporosis.Methods: We conducted a systematic review of articles published in PubMed, Medline or EMBASE through May 2017 to identify studies looking at prevalence of CD in patients with osteoporosis. Search terms included "coeliac disease" combined with fractures, bone disease, bone density, densitometry, "osteoporos", "osteomal", "osteodys" or "dexa" or "dxa" or "skelet". Non-English papers with English-language abstracts were included. We used fixed-effects inverse variance-weighted models, and tested heterogeneity through subgroup analysis as well as through meta-regression.Results: We identified eight relevant studies, comprising data from 3188 individuals with osteoporosis. Of these, 59 individuals (1.9%) had CD. A weighted pooled analysis demonstrated biopsy-confirmed CD in 1.6% (95% CI=1.1%-2.0%) of individuals with osteoporosis. The heterogeneity was moderate (I-2=40.1%), and influenced by the underlying CD prevalence in the general population. After adding four studies (n=814) with CD defined as positive tissue transglutaminase or endomysial antibodies, the pooled prevalence was comparable (1.6%; 95% CI=1.2%-2.0%).Conclusions: About 1 in 62 individuals with osteoporosis, or 1.6%, have biopsy-verified CD. This prevalence is comparable to that in the general population. These findings argue against routinely screening patients with osteoporosis for CD, which is contrary to current guideline recommendations. Additional studies are needed to determine the true utility of such screening programs.
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