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Sökning: WFRF:(Sørensen Henrik Toft)

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1.
  • Andersen, Sören M., et al. (författare)
  • A scalable route to 5-substituted 3-isoxazolol fibrinolysis inhibitor AZD6564
  • 2014
  • Ingår i: Organic Process Research & Development. - 1083-6160 .- 1520-586X. ; 18:8, s. 952-959
  • Tidskriftsartikel (refereegranskat)abstract
    • <p>A practical and chromatography-free multikilogram synthesis of a 3-isoxazolol containing antifibrinolytic agent, AZD6564, has been developed in eight steps and 7% overall yield starting from methyl 2-chloroisonicotinate. Highlights in the synthesis are a Negishi coupling and an enzymatic resolution of a racemic ester. </p>
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2.
  • Axelrad, Jordan E., et al. (författare)
  • Inflammatory bowel disease and risk of small bowel cancer : a binational population-based cohort study from Denmark and Sweden
  • 2020
  • Ingår i: Gut. - BMJ Publishing Group Ltd. - 0017-5749 .- 1468-3288.
  • Tidskriftsartikel (refereegranskat)abstract
    • <p><strong>OBJECTIVE:</strong> Crohn's disease (CD) is associated with increased risk of small bowel cancer (SBC), but previous studies have been small. We aimed to examine the risk of incident SBC and death from SBC in patients with inflammatory bowel disease (IBD).</p><p><strong>DESIGN:</strong> In a binational, population-based cohort study from Sweden and Denmark of patients with IBD during 1969-2017 and matched reference individuals from the general population, we evaluated the risk of incident SBC and death from SBC. Cox regression was used to estimate adjusted hazard ratios (aHRs).</p><p><strong>RESULTS:</strong> We identified 161 896 individuals with IBD (CD: 47 370; UC: 97 515; unclassified IBD: 17 011). During follow-up, 237 cases of SBC were diagnosed in patients with IBD (CD: 24.4/100 000 person-years; UC: 5.88/100 000 person-years), compared with 640 cases in reference individuals (2.81/100 000 person-years and 3.32/100 000 person-years, respectively). This corresponded to one extra case of SBC in 385 patients with CD and one extra case in 500 patients with UC, followed up for 10 years. The aHR for incident SBC was 9.09 (95% CI 7.34 to 11.3) in CD and 1.85 (95% CI 1.43 to 2.39) in UC. Excluding the first year after an IBD diagnosis, the aHRs for incident SBC decreased to 4.96 in CD and 1.69 in UC. Among patients with CD, HRs were independently highest for recently diagnosed, childhood-onset, ileal and stricturing CD. The relative hazard of SBC-related death was increased in both patients with CD (aHR 6.59, 95% CI 4.74 to 9.15) and patients with UC (aHR 1.57; 95% CI 1.07 to 2.32).</p><p><strong>CONCLUSION:</strong> SBC and death from SBC were more common in patients with IBD, particularly among patients with CD, although absolute risks were low.</p>
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3.
  • Bjørge, Tone, et al. (författare)
  • Reproductive history and risk of colorectal adenocarcinoma in parous women a Nordic population-based case-control study
  • 2016
  • Ingår i: British Journal of Cancer. - 0007-0920 .- 1532-1827. ; 115:11, s. 1416-1420
  • Tidskriftsartikel (refereegranskat)abstract
    • <p>Background: Data are conflicting regarding the role of endogenous sex hormones in colorectal carcinogenesis. In this large population-based study, we pooled data from birth and cancer registries in four Nordic countries, to evaluate the risk of colorectal adenocarcinoma in relation to women's reproductive history. Methods: We conducted a population-based case-control study among women registered in Nordic birth registries. The study included colorectal adenocarcinoma cases diagnosed in Denmark, Finland, Norway, and Sweden during 1967-2013 and up to 10 matched controls per case, in total 22 185 cases and 220 246 controls. Odds ratios (ORs) with 95% confidence intervals (95% CIs) were derived from conditional logistic regression models. We had limited information available on possible confounders. Results: We found no evidence for associations between colorectal adenocarcinoma and parity, age at first and last birth, and time since first and last birth. The risk estimates were also close to unity for specific cancer subsites (proximal and distal colon and rectum). As well, when the analyses were stratified on menopausal status, parity, and mother's year of birth, no indication of associations was found. Conclusions: In this large, Nordic population-based study, no evidence for associations was found between women's reproductive history and colorectal adenocarcinoma in parous women.</p>
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4.
  • Christensen, Steffen, et al. (författare)
  • Preadmission statin use and one-year mortality among patients in intensive care : a cohort study
  • 2010
  • Ingår i: Critical Care. - 1364-8535 .- 1466-609X. ; 14:2, s. R29
  • Tidskriftsartikel (refereegranskat)abstract
    • <p>INTRODUCTION: Statins reduce risk of cardiovascular events and have beneficial pleiotropic effects; both may reduce mortality in critically ill patients. We examined whether statin use was associated with risk of death in general intensive care unit (ICU) patients. METHODS: Cohort study of 12,483 critically ill patients &gt; 45 yrs of age with a first-time admission to one of three highly specialized ICUs within the Aarhus University Hospital network, Denmark, between 2001 and 2007. Statin users were identified through population-based prescription databases. We computed cumulative mortality rates 0-30 days and 31-365 days after ICU admission and mortality rate ratios (MRRs), using Cox regression analysis controlling for potential confounding factors (demographics, use of other cardiovascular drugs, comorbidity, markers of social status, diagnosis, and surgery). RESULTS: 1882 (14.3%) ICU patients were current statin users. Statin users had a reduced risk of death within 30 days of ICU admission [users: 22.1% vs. non-users 25.0%; adjusted MRR = 0.76 (95% confidence interval (CI): 0.69 to 0.86)]. Statin users also had a reduced risk of death within one year after admission to the ICU [users: 36.4% vs. non-users 39.9%; adjusted MRR = 0.79 (95% CI: 0.73 to 0.86)]. Reduced risk of death associated with current statin use remained robust in various subanalyses and in an analysis using propensity score matching. Former use of statins and current use of non-statin lipid-lowering drugs were not associated with reduced risk of death. CONCLUSIONS: Preadmission statin use was associated with reduced risk of death following intensive care. The associations seen could be a pharmacological effect of statins, but unmeasured differences in characteristics of statin users and non-users cannot be entirely ruled out.</p>
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5.
  • Everhov, Åsa H., et al. (författare)
  • Inflammatory bowel disease and pancreatic cancer : a Scandinavian register-based cohort study 1969-2017
  • 2020
  • Ingår i: Alimentary Pharmacology and Therapeutics. - John Wiley & Sons. - 0269-2813 .- 1365-2036. ; 52:1, s. 143-154
  • Tidskriftsartikel (refereegranskat)abstract
    • <p><strong>Background</strong>: Patients with inflammatory bowel disease (IBD) have an increased risk of cancer.</p><p><strong>Aim</strong>: To assess the risk of pancreatic cancer in IBD compared to the general population.</p><p><strong>Methods</strong>: Patients with incident IBD 1969-2017 were identified in Danish and Swedish National Patient Registers and through biopsy data, and were matched to IBD-free reference individuals by sex, age, place of residence and year of IBD diagnosis. We linked data to Cancer and Causes of Death Registers and examined the absolute and relative risks of pancreatic cancer and pancreatic cancer death.</p><p><strong>Results</strong>: Among 161 926 patients followed for 2 000 951 person years, 442 (0.27%) were diagnosed with pancreatic cancer compared to 3386 (0.21%) of the 1 599 024 reference individuals. The 20-year cumulative incidence was 0.34% (95% confidence interval 0.30-0.38) vs 0.29% (0.28-0.30). The incidence rate was 22.1 (20.1-24.2)/100 000 person years in the patients (excluding the first year of follow-up: 20.8 [18.8-23.0]), and 16.6 (16.0-17.2) in the reference individuals. The hazard ratio (HR) for pancreatic cancer was increased overall: 1.43 (1.30-1.58), in subtypes (Crohn's disease: 1.44 [1.18-1.74]; ulcerative colitis: 1.35 [1.19-1.53]; IBD unclassified: 1.99 [1.50-2.64]) and especially in IBD patients with primary sclerosing cholangitis: 7.55 (4.94-11.5). Patients and reference individuals with pancreatic cancer did not differ in cancer stage (P = 0.17) or pancreatic cancer mortality (HR 1.07 [0.95-1.21]).</p><p><strong>Conclusions</strong>: Patients with IBD had an excess risk of pancreatic cancer, in particular patients with primary sclerosing cholangitis. However, the cumulative incidence difference after 20 years was small: 0.05%, that is, one extra pancreatic cancer per 2000 IBD patients.</p>
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6.
  • Hansdotter Andersson, Pernilla, et al. (författare)
  • The COLOFOL trial: study design and comparison of the study population with the source cancer population.
  • 2016
  • Ingår i: Clinical Epidemiology. - Dove Press. - 1179-1349. ; 8, s. 15-21
  • Tidskriftsartikel (refereegranskat)abstract
    • The COLOFOL trial, a prospective randomized multicenter trial comparing two follow-up regimes after curative surgical treatment for colorectal cancer, focuses on detection of asymptomatic recurrences. This paper aims to describe the design and recruitment procedure in the COLOFOL trial, comparing demographic characteristics between randomized patients and eligible patients not included in the study.
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7.
  • Olén, Ola, et al. (författare)
  • Colorectal cancer in Crohn's disease : a Scandinavian population-based cohort study
  • 2020
  • Ingår i: The Lancet Gastroenterology & Hepatology. - Elsevier. - 2468-1253. ; 5:5, s. 475-484
  • Tidskriftsartikel (refereegranskat)abstract
    • <p><strong>Background</strong>: Crohn's disease is a risk factor for colorectal cancer (CRC). However, available studies reflect older treatment and surveillance strategies, and most have assessed risks for incident CRC without taking surveillance and lead-time bias into account. Such biases can be accounted for by assessing CRC incidence by tumour stage and CRC mortality by tumour stage. We aimed to assess rates of incident CRC and CRC mortality among patients with Crohn's disease compared with the general population.</p><p><strong>Methods</strong>: For this nationwide register-based cohort study, we used International Classification of Disease codes in national patient registers and pathology reports to identify incident cases of Crohn's disease. In Denmark we searched for incident cases between January, 1977, and December, 2011, and in Sweden between January, 1969, and December, 2017. For each patient with Crohn's disease, we identified up to ten reference individuals in national population registers and matched them by sex, age, calendar year, and place of residence. Matched reference individuals had to be alive and free of inflammatory bowel disease at the start of follow-up of index patients with Crohn's disease, and stopped contributing to reference person-years if they were diagnosed with inflammatory bowel disease. Our main outcome was death from CRC (main or contributory cause of death) as captured in the cause-of-death registers. Our secondary outcome was incident CRC, as defined by the cancer registers. We used Cox regression to estimate hazard ratios (HRs) for incident CRC and CRC mortality, taking tumour stage into account. We used a series of Cox models to estimate cause-specific HRs of the different competing outcomes (CRC diagnosis, CRC death, and other causes of death) and adjusted for tumour stage at CRC diagnosis.</p><p><strong>Findings</strong>: During the 1969-2017 study period, we identified 47 035 patients with incident Crohn's disease (13 056 in Denmark and 33 979 in Sweden) and 463 187 matched reference individuals. During follow-up, 296 (0.47 per 1000 person-years) CRC deaths occurred among individuals with Crohn's disease compared with 1968 (0.31 per 1000 person-years) in reference individuals, corresponding to an overall adjusted HR of 1.74 (1.54-1.96). 499 (0.82 per 1000 person-years) cases of incident CRC were diagnosed in patients with Crohn's disease compared with 4084 (0.64 per 1000 person-years) cases in reference individuals, corresponding to an overall adjusted HR of 1.40 (95% CI 1. 27-1.53). Patients with Crohn's disease who were diagnosed with CRC were at increased risk of CRC mortality compared with reference individuals also diagnosed with CRC (HR 1.42 [1.16-1.75] when adjusted for tumour stage), and tumour stage at CRC diagnosis did not differ between groups (p=0.27). Patients with Crohn's disease who had follow-up of 8 years or longer or who were diagnosed with primary sclerosing cholangitis (PSC) and hence were potentially eligible for CRC surveillance had an increased overall risk of CRC death (HR 1.40 [1.16-1.68]) or CRC diagnosis (HR 1.12 [0. 98-1. 28]). However, in patients potentially eligible for CRC surveillance we only found significantly increased risks in patients diagnosed with Crohn's disease before the age of 40 years, patients with disease activity in the colon only, or patients with PSC.</p><p><strong>Interpretation</strong>: Patients with Crohn's disease are at increased risk of CRC diagnosis and CRC death. Patients with Crohn's disease who have CRC have a higher mortality than patients without Crohn's disease who are also diagnosed with CRC. CRC surveillance should likely be focused on patients diagnosed with Crohn's disease before the age of 40 years, on patients with colon inflammation, and on those who have PSC.</p>
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8.
  • Olén, Ola, et al. (författare)
  • Colorectal cancer in ulcerative colitis : a Scandinavian population-based cohort study
  • 2020
  • Ingår i: The Lancet. - Elsevier. - 0140-6736 .- 1474-547X. ; 395:10218, s. 123-131
  • Tidskriftsartikel (refereegranskat)abstract
    • <p><strong>Background</strong>: Ulcerative colitis (UC) is a risk factor for colorectal cancer (CRC). However, available studies reflect older treatment and surveillance paradigms, and most have assessed risks for incident CRC without taking surveillance and lead-time bias into account, such as by assessing CRC incidence by tumour stage, or stage-adjusted mortality from CRC. We aimed to compare both overall and country-specific risks of CRC mortality and incident CRC among patients with UC.</p><p><strong>Methods</strong>: In this population-based cohort study of 96 447 patients with UC in Denmark (n=32 919) and Sweden (n=63 528), patients were followed up for CRC incidence and CRC mortality between Jan 1, 1969, and Dec 31, 2017, and compared with matched reference individuals from the general population (n=949 207). Patients with UC were selected from national registers and included in the analysis if they had two or more records with a relevant International Classification of Disease in the patient register (in the country in question) or one such record plus a colorectal biopsy report with a morphology code suggestive of inflammatory bowel disease. For every patient with UC, we selected matched reference individuals from the total population registers of Denmark and Sweden, who were matched for sex, age, birth year, and place of residence. We used Cox regression to compute hazard ratios (HRs) for incident CRC, and for CRC mortality, taking tumour stage into account.</p><p><strong>Findings</strong>: During follow-up, we observed 1336 incident CRCs in the UC cohort (1.29 per 1000 person-years) and 9544 incident CRCs in reference individuals (0.82 per 1000 person-years; HR 1.66, 95% CI 1.57-1.76). In the UC cohort, 639 patients died from CRC (0.55 per 1000 person-years), compared with 4451 reference individuals (0.38 per 1000 person-years; HR 1.59, 95% CI 1.46-1.72) during the same time period. The CRC stage distribution in people with UC was less advanced (p&lt;0.0001) than in matched reference individuals, but taking tumour stage into account, patients with UC and CRC remained at increased risk of CRC death (HR 1.54, 95% CI 1.33-1.78). The excess risks declined over calendar periods: during the last 5 years of follow-up (2013-17, Sweden only), the HR for incident CRC in people with UC was 1.38 (95% CI 1.20-1.60, or one additional case per 1058 patients with UC per 5 years) and the HR for death from CRC was 1.25 (95% CI 1.03-1.51, or one additional case per 3041 patients with UC per 5 years).</p><p><strong>Interpretation</strong>: Compared with those without UC, individuals with UC are at increased risk of developing CRC, are diagnosed with less advanced CRC, and are at increased risk of dying from CRC, although these excess risks have declined substantially over time. There still seems to be room for improvement in international surveillance guidelines.</p>
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9.
  • Ording, Anne Gulbech, et al. (författare)
  • Hospital Recorded Morbidity and Breast Cancer Incidence A Nationwide Population-Based Case-Control Study
  • 2012
  • Ingår i: PLoS ONE. - 1932-6203 .- 1932-6203. ; 7:10
  • Tidskriftsartikel (refereegranskat)abstract
    • <p>Introduction: Chronic diseases and their complications may increase breast cancer risk through known or still unknown mechanisms, or by shared causes. The association between morbidities and breast cancer risk has not been studied in depth. Methods: Data on all Danish women aged 45 to 85 years, diagnosed with breast cancer between 1994 and 2008 and data on preceding morbidities were retrieved from nationwide medical registries. Odds ratios (OR) and 95% confidence intervals (CI) were estimated using conditional logistic regression associating the Charlson comorbidity score (measured using both the original and an updated Charlson Comorbidity Index (CCI)) with incident breast cancer. Furthermore, we estimated associations between 202 morbidity categories and incident breast cancer, adjusting for multiple comparisons using empirical Bayes (EB) methods. Results: The study included 46,324 cases and 463,240 population controls. Increasing CCI score, up to a score of six, was associated with slightly increased breast cancer risk. Among the Charlson diseases, preceding moderate to severe renal disease (OR = 1.25, 95% CI: 1.06, 1.48), any tumor (OR = 1.17, 95% CI: 1.10, 1.25), moderate to severe liver disease (OR = 1.86, 95% CI: 1.32, 2.62), and metastatic solid tumors (OR = 1.49, 95% CI: 1.17, 1.89), were most strongly associated with subsequent breast cancer. Preceding myocardial infarction (OR = 0.89, 95% CI: 0.81, 0.99), connective tissue disease (OR = 0.87, 95% CI: 0.80, 0.94), and ulcer disease (OR = 0.91, 95% CI: 0.83, 0.99) were most strongly inversely associated with subsequent breast cancer. A history of breast disorders was associated with breast cancer after EB adjustment. Anemias were inversely associated with breast cancer, but the association was near null after EB adjustment. Conclusions: There was no substantial association between morbidity measured with the CCI and breast cancer risk.</p>
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