| 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. |
- Samuelsson, John, 1981-
(författare)
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Metabolic Control, Morbidity and Mortality in Type 1 Diabetes with Onset in Childhood/Adolescence
- 2024
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Aim: The overall aim of this thesis was to study mortality in individuals with onset of type 1 diabetes (T1D) in childhood and adolescence in Sweden, related to clinical characteristics such as metabolic control in childhood/adolescence and comorbidity. Methods: All studies in this thesis were register-based observational studies using a nationwide and population-based quality register, the paediatric part of the Swe-dish National Diabetes Register (NDR), for identification and collection of clinical data of individuals with T1D diagnosed before 18 years of age. Study I included 8084 individuals between 2000 and 2014, and compared these during follow-up based on HbA1c at onset of T1D. In studies II and IV 16,537 individuals with T1D registered from 2000 to 2014 were identified. This population was merged with the Swedish Cause of Death register (CDR) to identify deceased individuals during the study period and retrieve causes of death. In study II, the study period was set between 2006 and 2014, including 12,652 individuals. Standardised mortality rates (SMRs) were calculated using data from the Swedish population register. Study III included 15,188 individuals with onset of T1D between 2000 and 2019. Five randomly selected control individuals from the Swedish population were matched to each individual with T1D. These cohorts were linked to the National Patient Register to retrieve ICD codes on autoimmune diseases (AIDs), and to the CDR to identify deceased individuals. Medical records were retrieved from treating clinics for all de-ceased individuals in study IV. Results: Individuals in the highest quintile of HbA1c at onset of T1D (>114 mmol/mol) had higher HbA1c during follow-up compared to the lowest quintile (<72 mmol/mol) at onset, but there was no significant correlation between individual HbA1c at onset and during follow-up. In study II, 68 individuals were identified as deceased, of which almost 40% died due to diabetes, mainly caused by acute complications. The overall SMR was 2.7 per 1000 person-year. Those who died due to diabetes had significantly elevated HbA1c in childhood compared to those who died from other causes or were still alive. In study III, almost 20% of individuals with T1D developed at least one other AID. Coeliac disease was the most common followed by thyroid disease. Individuals with an additional AID did not have worse outcome in terms of metabolic control or mortality risk. In study IV, after review, 72 individuals had information in the medical records which was possible to evaluate regarding cause of death. Hypoglycaemia was the cause of death in two individuals (2.8%) and ketoacidosis in eight individuals (11.1%). In 16 (22.2%) individuals with cause of death due to diabetes with coma, no conclusion on whether death was caused by hypoglycaemia or ketoacidosis could be drawn. HbA1c was significantly elevated both in childhood and in the last year before death in medical records in those deceased due to diabetes. Conclusions: High HbA1c at onset of T1D cannot be used as a predictor of future metabolic control in the individual child or adolescent. Children and adolescents with high HbA1c in childhood have an increased risk of premature mortality, mainly due to acute complications of T1D. Hypoglycaemia was uncommon as a cause of death, contributing for certain to only 2.8 % of the mortality. Individuals with T1D have a high risk of developing other AIDs from the onset of diabetes; however such comorbidity was not associated with worse outcome in terms of metabolic control or mortality risk.
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| 3. |
- 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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| 4. |
- 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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| 6. |
- 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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| 7. |
- Karlqvist, Sara, et al.
(författare)
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Comparative Risk of Serious Infection With Vedolizumab vs Anti-Tumor Necrosis Factor in Inflammatory Bowel Disease : Results From Nationwide Swedish Registers
- 2024
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Ingår i: American Journal of Gastroenterology. - : Blackwell Publishing. - 0002-9270 .- 1572-0241.
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Tidskriftsartikel (refereegranskat)abstract
- INTRODUCTION: We aimed to assess the risk of serious infection in patients with inflammatory bowel disease (IBD) treated with vedolizumab compared with those treated with anti-tumor necrosis factors (TNF) and the general population.METHODS: In this Swedish cohort study, treatment episodes were identified from nationwide health registers. We used Cox regression with propensity score-matched cohorts to estimate hazard ratios (HRs) for incident serious infections, defined as infections requiring hospital admission.RESULTS: During 1,376 treatment episodes in Crohn's disease, the rate of serious infections per 100 person-years (PY) was 5.18 (95% CI = 3.98-6.63) with vedolizumab vs 3.54 (95% CI = 2.50-4.85) with anti-TNF; HR = 1.72 (95% CI = 1.12-2.65), partly explained by more gastrointestinal infections. Compared with the rate of 0.75/100 PY (95% CI = 0.59-0.92) in a matched general population cohort, vedolizumab demonstrated higher risk (HR = 7.00; 95% CI = 5.04-9.72). During 1,294 treatment episodes in ulcerative colitis, the corresponding rates were 3.74/100 PY (95% CI = 2.66-5.11) with vedolizumab vs 3.42/100 PY (95% CI = 2.31-4.89) with anti-TNF; HR = 0.80 (95% CI = 0.47-1.36) during the initial 1.1 years and HR = 2.03 (95% CI = 0.65-6.32) after 1.1 years (truncated due to nonproportional hazards). Pneumonia accounted for 40% of all infections among anti-TNF, whereas no case was observed among vedolizumab episodes. Compared with the rate of 0.69/100 PYs (95% CI = 0.53-0.87) in a matched general population cohort, vedolizumab showed an HR of 5.45 (95% CI = 3.67-8.11).DISCUSSION: Vedolizumab was associated with increased risks of serious infections compared with anti-TNF in Crohn's disease but not in ulcerative colitis. Nonetheless, the panorama of serious infections seemed to differ between the drugs. Our findings underscore the importance of clinical awareness of infections and the safety profile of the 2 therapies.
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| 8. |
- Mitselou, Niki, 1982-
(författare)
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Preterm birth and allergic disease
- 2022
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Allergic diseases are very common in children and young adults, while there is an ongoing interest worldwide in exploring the early origins of these conditions. The perinatal period is considered crucial as it encompasses the maturation of gut microbiota and the establishment of an efficient immunoregulation. Early-life factors might be the key drivers of an altered immune response, sometimes leading to sensitization and allergic disease. Preterm birth is believed to affect the risk of immune-mediated diseases, while a delayed and altered gut microbiota composition and diversity following caesarean delivery might influence the induction of tolerance.In the first paper, using a large population database, we found that caesarean delivery increased the risk of allergic rhinitis (AR) in offspring, while moderately preterm birth (≥32–36 weeks of gestation) was associated with a slightly elevated risk. No association was observed between post-term birth (≥42 weeks) and AR. There also seems to be a positive association between large for gestational age, low 5-minute Apgar score (<7) and AR. In the second paper, we used data from the BAMSE population-based birth cohort to assess the impact of gestational age at birth on future IgE sensitization. The study concluded that preterm birth (<37 weeks of gestation) was inversely associated with IgE sensitization to common food and/or inhalant allergens up to the age 24 years, while no association was found between postterm birth and IgE sensitization.Uncontrolled asthma and allergic disease in pregnancy are associated with poor pregnancy outcome. Current guidelines recommend against the initiation of allergen-specific immunotherapy (AIT) in pregnant patients, while welltolerated ongoing AIT might be continued. In the third paper, using national health-care registers, we found no association between AIT during pregnancy and risk of congenital malformations, preterm birth, caesarean delivery, stillbirth, or other adverse pregnancy outcomes.
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| 9. |
- 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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| 10. |
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