| 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. |
- Cao, Yang, Associate Professor, 1972-, et al.
(författare)
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The statistical importance of P-POSSUM scores for predicting mortality after emergency laparotomy in geriatric patients
- 2020
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Ingår i: BMC Medical Informatics and Decision Making. - : BioMed Central. - 1472-6947. ; 20:1
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Geriatric patients frequently undergo emergency general surgery and accrue a greater risk of postoperative complications and fatal outcomes than the general population. It is highly relevant to develop the most appropriate care measures and to guide patient-centered decision-making around end-of-life care. Portsmouth - Physiological and Operative Severity Score for the enumeration of Mortality and morbidity (P-POSSUM) has been used to predict mortality in patients undergoing different types of surgery. In the present study, we aimed to evaluate the relative importance of the P-POSSUM score for predicting 90-day mortality in the elderly subjected to emergency laparotomy from statistical aspects.METHODS: One hundred and fifty-seven geriatric patients aged ≥65 years undergoing emergency laparotomy between January 1st, 2015 and December 31st, 2016 were included in the study. Mortality and 27 other patient characteristics were retrieved from the computerized records of Örebro University Hospital in Örebro, Sweden. Two supervised classification machine methods (logistic regression and random forest) were used to predict the 90-day mortality risk. Three scalers (Standard scaler, Robust scaler and Min-Max scaler) were used for variable engineering. The performance of the models was evaluated using accuracy, sensitivity, specificity and area under the receiver operating characteristic curve (AUC). Importance of the predictors were evaluated using permutation variable importance and Gini importance.RESULTS: The mean age of the included patients was 75.4 years (standard deviation =7.3 years) and the 90-day mortality rate was 29.3%. The most common indication for surgery was bowel obstruction occurring in 92 (58.6%) patients. Types of post-operative complications ranged between 7.0-36.9% with infection being the most common type. Both the logistic regression and random forest models showed satisfactory performance for predicting 90-day mortality risk in geriatric patients after emergency laparotomy, with AUCs of 0.88 and 0.93, respectively. Both models had an accuracy > 0.8 and a specificity ≥0.9. P-POSSUM had the greatest relative importance for predicting 90-day mortality in the logistic regression model and was the fifth important predictor in the random forest model. No notable change was found in sensitivity analysis using different variable engineering methods with P-POSSUM being among the five most accurate variables for mortality prediction.CONCLUSION: P-POSSUM is important for predicting 90-day mortality after emergency laparotomy in geriatric patients. The logistic regression model and random forest model may have an accuracy of > 0.8 and an AUC around 0.9 for predicting 90-day mortality. Further validation of the variables' importance and the models' robustness is needed by use of larger dataset.
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| 3. |
- 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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| 4. |
- 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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| 5. |
- 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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| 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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| 8. |
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| 9. |
- 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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| 10. |
- Brand, Judith, 1984-, et al.
(författare)
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Maternal smoking during pregnancy and fractures in offspring : national register based sibling comparison study
- 2020
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Ingår i: The BMJ. - : BMJ Publishing Group Ltd. - 1756-1833. ; 368
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: To study the impact of maternal smoking during pregnancy on fractures in offspring during different developmental stages of life.DESIGN: National register based birth cohort study with a sibling comparison design.SETTING: Sweden.PARTICIPANTS: 1 680 307 people born in Sweden between 1983 and 2000 to women who smoked (n=377 367, 22.5%) and did not smoke (n=1 302 940) in early pregnancy. Follow-up was until 31 December 2014.MAIN OUTCOME MEASURE: Fractures by attained age up to 32 years.RESULTS: During a median follow-up of 21.1 years, 377 970 fractures were observed (the overall incidence rate for fracture standardised by calendar year of birth was 11.8 per 1000 person years). The association between maternal smoking during pregnancy and risk of fracture in offspring differed by attained age. Maternal smoking was associated with a higher rate of fractures in offspring before 1 year of age in the entire cohort (birth year standardised fracture rates in those exposed and unexposed to maternal smoking were 1.59 and 1.28 per 1000 person years, respectively). After adjustment for potential confounders the hazard ratio for maternal smoking compared with no smoking was 1.27 (95% confidence interval 1.12 to 1.45). This association followed a dose dependent pattern (compared with no smoking, hazard ratios for 1-9 cigarettes/day and >= 10 cigarettes/day were 1.20 (95% confidence interval 1.03 to 1.39) and 1.41 (1.18 to 1.69), respectively) and persisted in within-sibship comparisons although with wider confidence intervals (compared with no smoking, 1.58 (1.01 to 2.46)). Maternal smoking during pregnancy was also associated with an increased fracture incidence in offspring from age 5 to 32 years in whole cohort analyses, but these associations did not follow a dose dependent gradient. In within-sibship analyses, which controls for confounding by measured and unmeasured shared familial factors, corresponding point estimates were all close to null. Maternal smoking was not associated with risk of fracture in offspring between the ages of 1 and 5 years in any of the models.CONCLUSION: Prenatal exposure to maternal smoking is associated with an increased rate of fracture during the first year of life but does not seem to have a long lasting biological influence on fractures later in childhood and up to early adulthood.
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