| 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. |
- 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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| 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. |
- 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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| 5. |
- 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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| 6. |
- Bergh, Cecilia, 1972-, et al.
(författare)
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Shared unmeasured characteristics among siblings confound the association of Apgar score with stress resilience in adolescence
- 2019
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Ingår i: Acta Paediatrica. - : Wiley-Blackwell Publishing Inc.. - 0803-5253 .- 1651-2227. ; 108:11, s. 2001-2007
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Tidskriftsartikel (refereegranskat)abstract
- AIM: We investigated the association between low Apgar score, other perinatal characteristics and low stress resilience in adolescence. A within-siblings analysis was used to tackle unmeasured shared familial confounding.METHODS: We used a national cohort of 527,763 males born in Sweden between 1973 and 1992 who undertook military conscription assessments at mean age 18 years (17-20). Conscription examinations included a measure of stress resilience. Information on Apgar score and other perinatal characteristics was obtained through linkage with the Medical Birth Register. Analyses were conducted using ordinary least squares and fixed-effects linear regression models adjusted for potential confounding factors.RESULTS: Infants with a prolonged low Apgar score at five minutes had an increased risk of low stress resilience in adolescence compared to those with highest scores at one minute, with an adjusted coefficient and 95% confidence interval of -0.26 (-0.39, -0.13). The associations were no longer statistically significant when using within-siblings models. However, the associations with stress resilience and birthweight remained statistically significant in all analyses.CONCLUSION: The association with low Apgar score seems to be explained by confounding due to shared childhood circumstances among siblings from the same family, while low birthweight is independently associated with low stress resilience.
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| 7. |
- Cao, Yang, Associate Professor, 1972-, et al.
(författare)
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Predicting Long-Term Health-Related Quality of Life after Bariatric Surgery Using a Conventional Neural Network : A Study Based on the Scandinavian Obesity Surgery Registry
- 2019
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Ingår i: Journal of Clinical Medicine. - : MDPI. - 2077-0383. ; 8:12
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Tidskriftsartikel (refereegranskat)abstract
- Severe obesity has been associated with numerous comorbidities and reduced health-related quality of life (HRQoL). Although many studies have reported changes in HRQoL after bariatric surgery, few were long-term prospective studies. We examined the performance of the convolution neural network (CNN) for predicting 5-year HRQoL after bariatric surgery based on the available preoperative information from the Scandinavian Obesity Surgery Registry (SOReg). CNN was used to predict the 5-year HRQoL after bariatric surgery in a training dataset and evaluated in a test dataset. In general, performance of the CNN model (measured as mean squared error, MSE) increased with more convolution layer filters, computation units, and epochs, and decreased with a larger batch size. The CNN model showed an overwhelming advantage in predicting all the HRQoL measures. The MSEs of the CNN model for training data were 8% to 80% smaller than those of the linear regression model. When the models were evaluated using the test data, the CNN model performed better than the linear regression model. However, the issue of overfitting was apparent in the CNN model. We concluded that the performance of the CNN is better than the traditional multivariate linear regression model in predicting long-term HRQoL after bariatric surgery; however, the overfitting issue needs to be mitigated using more features or more patients to train the model.
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| 8. |
- Eriksson, Carl, 1981-, et al.
(författare)
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Impact of thiopurines on the natural history and surgical outcome of ulcerative colitis : a cohort study
- 2019
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Ingår i: Gut. - : BMJ Publishing Group Ltd. - 0017-5749 .- 1468-3288. ; 68:4, s. 623-632
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: Thiopurines are used as maintenance therapy in ulcerative colitis (UC), but whether these drugs influence the natural history of the disease is unknown. We aimed to assess the effect of thiopurines in terms of colectomy, hospital admission, progression in disease extent and anti-tumour necrosis factor (TNF) therapy within 10 years from initiation.DESIGN: Patients diagnosed with UC within the Örebro University Hospital catchment area, during 1963-2010, who initiated thiopurines (n=253) were included. To overcome the risk of confounding by indication, we compared patients who stopped treatment within 12 months because of an adverse reaction (n=76) with patients who continued therapy or discontinued due to other reasons (n=177) and assessed long-term outcomes using Cox regression with adjustment for potential confounding factors.RESULTS: The cumulative probability of colectomy within 10 years was 19.5% in tolerant patients compared with 29.0% in intolerant (adjusted HR 0.49; 95% CI 0.21 to 0.73). The probability of hospital admission was 34.0% in tolerant versus 56.2% in intolerant patients (adjusted HR 0.36; 95% CI 0.23 to 0.56). The risk for progression in disease extent was 20.4% in tolerant patients compared with 48.8% in intolerant (adjusted HR 0.47; 95% CI 0.21 to 1.06). Within 10 years, 16.1% of tolerant and 27.5% of intolerant patients received anti-TNF therapy (adjusted HR 0.49; 95% CI 0.26 to 0.92).CONCLUSION: Based on the novel approach of comparing patients tolerant and intolerant to thiopurines, we reveal that thiopurines have a profound beneficial impact of the natural history and long-term colectomy rates of UC.
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