| 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. |
- Sundh, Josefin, 1972-
(författare)
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Quality of life, mortality and exacerbations in COPD
- 2013
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Background: Risk factors for poor health related quality of life (HRQL), mortality and exacerbations in Chronic Obstructive Pulmonary Disease (COPD) need to be explored.Objectives: To examine associations of comorbidity and Body Mass Index (BMI) with HRQL using the Clinical COPD Questionnaire (CCQ); to examine the prognostic qualities of the multidimensional instrument DOSE index; to examine the association of health status estimated by the CCQ with mortality; and to examine management of exacerbations and subsequent exacerbation risk.Material: Randomly selected patients from primary and secondary care, usingthe COPD cohort of the PRAXIS study. Information was collected using apatient questionnaire, record review and a clinical questionnaire. Mortalitydata wereobtained from the National Board of Health and Welfare.Methods: Multiple linear regression analysis, survival analysis and standardisedmortality ratios.Results: Heart disease, depression and underweight were associated withhigher CCQ. A higher DOSE index was associated with higher mortality. Ahigher CCQ was associated with higher mortality risk and mortality risk wasraised compared with the general population. Exacerbation management inprimary care was not optimal. An extra scheduled visit to an asthma/COPDnurse was associated with a reduced risk of subsequent exacerbations.Conclusions: The influence of comorbidity on HRQL in COPD patients is important. The DOSE index is useful as it combines important issues in COPD management with prognostic qualities. Health status estimated by CCQ is predictive of mortality. Exacerbation management in primary care COPD patients needs to be optimised, and nurse led asthma/COPD clinics may be a way to optimise resources with possible beneficial effects on exacerbation risk. These results could be used to improve COPD care and to facilitate focusing resources for those at greatest risk.
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| 3. |
- Bergh, Cecilia, 1972-
(författare)
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Life-course influences on occurrence and outcome for stroke and coronary heart disease
- 2017
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Although typical clinical onset does not occur until adulthood, cardiovascular disease (CVD) may have a long natural history with accumulation of risks beginning in early life and continuing through childhood and into adolescence and adulthood. Therefore, it is important to adopt a life-course approach to explore accumulation of risks, as well as identifying age-defined windows of susceptibility, from early life to disease onset. This thesis examines characteristics in adolescence and adulthood linked with subsequent risk of CVD. One area is concerned with physical and psychological characteristics in adolescence, which reflects inherited and acquired elements from childhood, and their association with occurrence and outcome of subsequent stroke and coronary heart disease many years later. The second area focuses on severe infections and subsequent delayed risk of CVD. Data from several Swedish registers were used to provide information on a general population-based cohort of men. Some 284 198 males, born in Sweden from 1952 to 1956 and included in the Swedish Military Conscription Register, form the basis of the study cohort for this thesis. Our results indicate that characteristics already present in adolescence may have an important role in determining long-term cardiovascular health. Stress resilience in adolescence was associated with an increased risk of stroke and CHD, working in part through other CVD factors, in particular physical fitness. Stress resilience, unhealthy BMI and elevated blood pressure in adolescence were also associated with aspects of stroke severity among survivors of a first stroke. We demonstrated an association for severe infections (hospital admission for sepsis and pneumonia) in adulthood with subsequent delayed risk of CVD, independent of risk factors from adolescence. Persistent systemic inflammatory activity which could follow infection, and that might persist long after infections resolve, represents a possible mechanism. Interventions to protect against CVD should begin by adolescence; and there may be a period of heightened susceptibility in the years following severe infection when additional monitoring and interventions for CVD may be of value.
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| 4. |
- 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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| 5. |
- 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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| 6. |
- Larsson, Matz, 1955-
(författare)
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Secondary exposure to inhaled tobacco products
- 2008
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Även andra individer än rökaren kan påverkas av tobaksrökning. Syftet med denna avhandling var att undersöka några sådana effekter. Studierna omfattar såväl passiv rökning som exponering under graviditet. Mer specifikt handlar studierna om: · Exponering för passiv rökning under barndomen och samband med luftvägssymtom och allergi senare i livet. · Passiv rökning i vuxen ålder och samband med luftvägssymtom. · Exponering hos serveringspersonal och effekter av lagstiftning mot tobaksrökning. · Rökning under graviditet och kontroll och koordination av handrörelser hos barn. Passiv rökning i barndomen hade en koppling till ökad risk för astma och allergi. Passiv rökning hos vuxna var kopplat till förekomst av andnings- och luftvägssymtom på ett dosberoende vis. Besvär i andningsvägar och slemhinnor minskade avsevärt hos icke rökande serveringspersonal efter rökförbudet på restauranger som infördes den 1 juni 2005. Mammans rökning under graviditet var kopplad till nedsatt handkontroll och handkoordination hos avkomman. Sambandet var tydligast för vänsterhanden och pojkarnas handfunktion påverkades betydligt mer än flickornas. Fynden stödjer att rökning under graviditet kan påverka nervsystemets utveckling i negativ riktning. Ett flertal oönskade effekter kan således drabba dem som är nära rökare under någon period i livet och resultaten understryker vikten av att förebygga sådan exponering.
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| 7. |
- 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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| 8. |
- Melinder, Carren Anyango, 1975-
(författare)
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Physical and psychological characteristics in adolescence and risk of gastrointestinal disease in adulthood
- 2017
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Background and objectives: Physical fitness and stress resilience may influence the risk of gastrointestinal (GI) disease. High physical fitness level may reduce levels of systemic inflammation while psychosocial stress exposure can increase inflammation levels and intestinal permeability. The main objectives are to evaluate if poorer physical fitness and stress resilience in adolescence are associated with a raised risk of inflammatory bowel disease (IBD), peptic ulcer disease (PUD) and GI infections in adulthood and to assess evidence of causality.Materials and methods: Swedish registers provided information on a cohort of approximately 250,000 men who underwent military conscription assessments in late adolescence (1969 –1976) with follow-up until December 2009 (up to age 57 years). Cox regression evaluated the associations of physical fitness and stress resilience in adolescence with subsequent GI disease risk in adulthood.Results and conclusions: IBD: Poor physical fitness was associated with an increased risk of IBD. The association may be explained (in part) by prodromal disease activity reducing exercise capacity and therefore fitness. Low stress resilience was associated with an increased risk of receiving an IBD diagnosis. Stress may not be an important cause of IBD but may increase the likelihood of conversion from subclinical to symptomatic disease. PUD: Low stress resilience was associated with an increased risk of PUD. This may be explained by a combination of physiological and behavioural mechanisms that increase susceptibility to H. pylori infections and other risk factors. GI infections: Low stress resilience was associated with a reduced risk of GI infections, including enteric infections rather than the hypothesised increased risk.
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| 9. |
- 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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| 10. |
- 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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