| 1. |
- Eriksson, Carl, 1981-
(författare)
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Epidemiological and therapeutic aspects of Inflammatory Bowel Disease
- 2018
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Introduction: The two main forms of inflammatory bowel disease (IBD) are Crohn’s disease and ulcerative colitis. These are chronic inflammatory disorders, mainly affecting the gastrointestinal tract.Aims: The overall aims of this thesis were to study the epidemiology of ulcerative colitis in Örebro, Sweden; to examine certain aspects of anaemia in IBD; and to determine the clinical effectiveness of medical treatments.Material and methods: Cohort studies with the sampling frame defined by the geographic boundaries of the primary catchment area of Örebro University Hospital (Papers I‒III), or by the entire IBD population in Sweden registered in the Swedish national quality registry for IBD (SWIBREG; paper IV), were performed to determine the epidemiology of ulcerative colitis, the incidence and prevalence of anaemia in IBD, and the clinical effectiveness of thiopurine drugs and vedolizumab in routine care.Results: A fivefold increase in the incidence and a tenfold increase in the prevalence of ulcerative colitis was observed in Örebro during the past 50 years. In parallel, the prognosis, in terms of risk for colectomy within 10 years from diagnosis, improved during the same time period. Earlier and more widespread use of thiopurine drugs may have contributed to the decrease in colectomies. Anaemia is common in IBD, particularly in Crohn’s disease. Vedolizumab, a new drug targeting leucocyte migration to the gut, appears to be well tolerated and effective in Swedish real-world IBD care.Conclusion: Ulcerative colitis is on the rise, and data from Örebro indicate that the number of IBD patients in Sweden already exceeds 70,000. Improved knowledge of long-term outcomes of medical therapy may have far-reaching implications for future IBD management.
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| 2. |
- Karlqvist, Sara, 1992-
(författare)
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Clinical aspects of biological treatment in inflammatory bowel disease
- 2024
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Inflammatory bowel disease (IBD) including its main subtypes, Crohn’s disease and ulcerative colitis, is a chronic and recurrent inflammatory condition that affects the entire gastrointestinal system. Biological treatment has revolutionized the therapeutic armamentarium in the past two decades. The growing number of therapeutic options advocates for head-to-head comparisons, evaluation in clinical practice and assessment of safety. Therefore, this thesis aims to evaluate different facets of biological treatment in real-world cohorts.In Paper I, we examined the potential effectiveness of golimumab in Crohn’s disease using data from The Swedish National Quality Register for Inflammatory Bowel Disease (SWIBREG). The findings indicate a drug retention rate of 35% after a median follow-up of 89 (IQR: 32–158) weeks. Paper II constituted a prospective, multicentre, observational cohort study investigating the effectiveness of vedolizumab and its impact on quality of life in a Swedish clinical setting. The percentage of patients in clinical remission after 52 weeks was 41% for Crohn's disease and 47% for ulcerative colitis. Improvements in biochemical markers and health-related quality of life measures were observed at 12 and 52 weeks in both subtypes of IBD. In Paper III, second-line biological treatments were compared in propensity score-matched cohorts based on combined data from multiple high-quality Swedish nationwide registers. The effectiveness and safety of secondline anti-TNF and vedolizumab were similar at 12 months in Crohn’s disease (n=198) and ulcerative colitis (n=202). Based on propensity score-matched data from nationwide health registers, Paper IV showed that vedolizumab was associated with higher hazard ratios of serious infections than anti-TNF in Crohn’s disease but not in ulcerative colitis.To conclude, this thesis suggests that golimumab might have a role in treating Crohn’s disease. It also increased knowledge about the real-world effectiveness of vedolizumab. Lastly, the thesis underscored aspects of efficacy and safety when contrasting vedolizumab with anti-TNF.
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| 3. |
- Kennedy, Beatrice, 1982-
(författare)
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Childhood bereavement, stress resilience, and cancer risk : an integrated register-based approach
- 2018
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Accumulating evidence suggests that psychosocial stress and susceptibility to stressful exposures – stress resilience – influence the risk of various health outcomes, but the potential link with cancer occurrence is unclear. The aims of this thesis were to test if loss of a close relative, a marker of severe psychological stress, and stress resilience measured during late adolescence are associated with cancer risk later in life, as well as to explore potential underlying mechanisms. National registers provided information on childhood bereavement, defined as death of a first-degree relative, as well as a measure of psychological functioning relevant to stress resilience that was obtained from mandatory military enlistment assessments. In a cohort comprising all individuals born in Sweden during 1961-2002, we found that bereavement during childhood (up to age 18 years) was associated with increased risks of HPVrelated malignancies and pancreatic cancer. Parental loss during early adulthood (ages 18-40 years) also entails a raised risk of pancreatic cancer as well as for gastric and lung cancer. In a cohort of men born during 1973-1983, we observed that childhood bereavement is also associated with low stress resilience during late adolescence. In our third cohort study, comprising men born during 1952-1956, we found that low stress resilience compared with high, was associated with 5-fold and 3-fold increased risks of subsequent liver and lung cancer, respectively. In contrast, low stress resilience is associated with reduced risks for prostate cancer and malignant melanoma. Finally, in a cohort of twin conscripts born during 1959-1985 who completed a survey in 2005- 2006 covering use of addictive substances, we found that low stress resilience was also associated with a raised occurrence of hazardous use of alcohol, alcohol dependence, cigarette smoking and nicotine dependence, as well as with other drug use. We conclude that the observed links with cancer risk for stressful exposures and low stress resilience, may be explained, at least in part, by disadvantageous health behavior.
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| 4. |
- Lybeck, Charlotte, 1979-
(författare)
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Towards the elimination of hepatitis C : identifying the infected population, and remaining hepatitis C related risks after successful treatment
- 2022
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Chronic Hepatitis C virus (HCV) infection can lead to liver fibrosis and cirrhosis with increased risk of hepatocellular carcinoma (HCC) and liver failure. The World Health Organisation (WHO) has set a goal to eliminate viral hepatitis as a global health threat by 2030. To reach this goal for HCV we need to prevent new infections and identify and treat the infected population. Individuals with pre-treatment cirrhosis still have an elevated risk for HCC after HCV cure. This thesis aims to assess the health outcomes after cured HCV infection, study HCV prevalence and find a way to identify undiagnosed infections.In Paper I, 97 patients were followed through clinical visits (n=54) or through national registers (n=43) to study the long-term outcomes after cure from HCV and to assess the presence and impact of occult HCV infection (OCI). Three non-cirrhotic patients were diagnosed with HCC 8-11 years after HCV cure. Two patients had OCI at 8-9 years after cure. They had liver fibrosis stage 2, but no association with HCC. In Paper II, pregnant women (n=4,108) and partners (n=1,027) at antenatal clinics in southern Stockholm and Örebro County were tested for HCV and interviewed about risk factors to assess prevalence and evaluate screening strategies to identify undiagnosed infections. Anti-HCV prevalence was 0.7% and 0.4% were viraemic. The most effective risk factor-based screening was to ask for drug use, country of birth, and having a partner with HCV. Paper III presents a nationwide register study of the risk of extrahepatic cancer (EHC) the first 3 years after HCV treatment with direct acting antiviral (DAAs). We compared 4,013 DAA-treated, with 3,071 interferon-treated and 12,601 untreated patients. No increased risk for EHC was found after adjustments for age and comorbidities. An increased EHC risk in DAA-treated compared with general population was seen. Paper IV presents a register based study of the risk of HCC and association with pre-treatment liver stiffness measurement (LSM) in 7,227 HCV infected patients cured by DAAs. We found that pre-treatment LSM values correlated well with HCC risk. The incidence rate for patients with LSM values ≥12.5 kPa and <12.5 kPa was 1.6 and 0.15/100 person years, respectively.To conclude, cured HCV infection usually leads to regression of fibrosis. The DAAs are safe and highly effective against HCV. However, the HCC risk remains elevated for many years after cure in cirrhotic and sometimes in non-cirrhotic patients. Furthermore, HCV screening of pregnant women and partners is useful to identify patients who would benefit from therapy.
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| 5. |
- Shrestha, Sarita, 1991-
(författare)
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Impact of age and inflammation on extraintestinal manifestations of inflammatory bowel disease
- 2024
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Inflammatory bowel disease (IBD), encompassing Crohn's disease and ulcerative colitis, is often complicated by extraintestinal manifestations (EIMs) that affect organs beyond the gastrointestinal tract. The EIMs can significantly impair quality of life and complicate disease management in patients with IBD. As the population ages, understanding the interplay between age, chronic inflammation, and EIMs becomes increasingly important for optimizing patient care and outcomes. Thus, the overall aim of the thesis was to assess the impact of age and inflammation on EIM of IBD.We conducted all studies using Swedish national registers. To evaluate the accuracy of the National patient register (NPR), we compared International classification of diseases (ICD) coded IBD data with clinical records from 1403 IBD patients. For investigating spondyloarthritis (SpA) comorbidity, a cohort of 39,203 IBD patients diagnosed between 2006-2016 and 390,490 matched reference individuals were analyzed. The familial risk of SpA was assessed among 147,080 first-degree relatives (FDRs) and 25,945 spouses of IBD patients. The influence of colectomy on SpA and other EIMs was studied in 3246 ulcerative colitis patients, comparing EIM rates before and after surgery.The NPR showed high positive predictive values (PPVs) for Crohn's disease (97%) and ulcerative colitis (98%) but a low PPV for IBD-unclassified (8%). Crohn's disease location and behaviour had variable PPVs, indicating frequent misclassification. A high PPV (95%) was observed for age at diagnosis of IBD. Patients with IBD had significantly higher relative risk estimates of SpA both before (odds ratio [OR]: 3.48) and after (hazard ratio [HR]: 7.15) IBD diagnosis compared to the general population. FDRs of IBD patients exhibited a higher risk of SpA (HR: 1.35). Spouses also had an elevated SpA risk, suggesting environmental influences. The highest risks were observed in Crohn's disease and pediatric-onset IBD. Post-colectomy, patients with ulcerative colitis experienced increased EIM rates (rate ratios [RR]: 1.83). In addition, de novo EIMs frequently occurred in patients with no history of EIMs before colectomy.The NPR is a reliable source for subtype of IBD, although improvements are needed for phenotypic accuracy. IBD significantly increases the risk of SpA. The elevated SpA risk among FDRs and spouses points to shared genetic and environmental factors. Colectomyin patients with ulcerative colitis does not mitigate the risk of EIMs, indicating a need for continued monitoring and management post-surgery. This thesis underscores the importance of comprehensive care approaches that address both gastrointestinal and extraintestinal challenges in IBD.
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| 6. |
- Sundin, Per-Ola, 1971-
(författare)
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A life-course approach to chronic kidney disease : risks and consequences
- 2019
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Successful primary prevention of chronic kidney disease (CKD) relies on understanding the pathways leading to established disease, including how they extend over the life-course. Projects in this thesis examine risk factors for CKD and consequences of impaired kidney function from a life-course perspective using routinely collected health-data in Swedish registers and research cohort data from the United Kingdom.The main findings regarding risk factors for CKD are, that markers of health and development determined at conscription assessment in adolescence, independently predict diagnosis of end-stage renal disease in middle age. We also identified a persistent increased risk of CKD following hospital admission with pneumonia in adulthood with highest magnitude risks in years immediately following infection, but still statistically significantly raised more than 15 years after the pneumonia episode. Our main findings relevant to predicting the consequences of impaired kidney function are that creatinine and cystatin C used clinically to estimate kidney function (estimated glomerular filtration rate, eGFR) have associations with increased mortality risk independent of GFR measured with an exogenous filtration marker (mGFR). If cystatin C and creatinine are combined, adding mGFR does not improve mortality risk prediction. Another important finding is that moderately reduced eGFR is only associated with a statistically significant increased mortality risk among individuals in the lowest third of the distribution of grip strength in a general population sample followed for 4-5 years, after adjustment for potential confounding factors.These results highlight the importance of adopting a life-course perspective when studying risk factors for CKD, since these associations can extend over different stages in the life-course. When assessing increased mortality risk associated with measures of GFR, combining cystatin and creatinine improves risk prediction. Potential effect modification across subgroups, including by grip strength, should be considered.
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| 7. |
- Udumyan, Ruzan, 1971-
(författare)
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Stress susceptibility, beta-blocker use and cancer survival
- 2020
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Accumulating evidence suggests that chronic stress may influence tumour biology through activation of neuroendocrine pathways and thus impair survival. However, measuring stressful exposures and their influence on health is challenging, partly due to substantial inter-individual variation in stress susceptibility. The thesis aimed to explore whether stress resilience and use of β-adrenergic receptor blockers, which are implicated in regulation of neuroendocrine stress response pathways, are linked to survival after a primary cancer diagnosis using data from Swedish national registers. In a cohort of male cancer patients born during 1952-1956 who had their stress resilience assessed during a mandatory conscription examination in late adolescence, low compared with high stress resilience was associated with a higher overall mortality rate. Statistically significant reductions in survival were observed among men with carcinomas of the oropharynx, prostate, upper respiratory tract, and Hodgkin’s lymphoma. In a cohort of patients diagnosed with pancreatic adenocarcinoma during 2006-2009, β-blocker users had a lower pancreatic cancer mortality rate than non-users, particularly among patients without distant metastases at diagnosis. In a cohort of patients diagnosed with non-small cell lung cancer during 2006-2014, there was no clear association between β-blocker use and lung cancer survival, but we cannot exclude the possibility of associations in some sub-groups defined by histology, stage and β-blocker types. In a cohort of patients diagnosed with hepatocellular carcinoma during 2006-2014, β-blocker use was associated with lower liver cancer mortality, particularly among patients with localised disease. A higher-magnitude inverse association was observed for non-selective β-blocker use. In conclusion, greater stress resilience and β-blocker use are associated with improved survival among patients with some cancer types, and this may be explained by a variety of pathways.
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