| 1. |
- Axelrad, Jordan E., et al.
(author)
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A Novel Method for Quantifying Intestinal Inflammatory Burden in Inflammatory Bowel Disease Using Register Data
- 2020
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In: Clinical Epidemiology. - : Dove Medical Press Ltd.. - 1179-1349. ; 12, s. 1059-1072
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Journal article (peer-reviewed)abstract
- Background: The Swedish Quality Register for Inflammatory Bowel Disease (SWIBREG) contains clinical data for the study of inflammatory bowel disease (IBD). The Epidemiology Strengthened by histoPathology Reports in Sweden (ESPRESSO) cohort was recently established for the study of gastrointestinal histopathology. We aimed to develop and validate a histology score from ESPRESSO using clinical information from SWIBREG, and secondarily, to evaluate the association of the score on IBD-related hospitalization.Methods: In a nationwide, population-based cohort study of patients with IBD during 1969-2017, we linked endoscopic inflammation in SWIBREG with histologic inflammation in ESPRESSO. We established a clinically interpretable model for predicting the endoscopic score from histology using scalable Bayesian rule lists to define a SNOMED-based histology score applicable to the ESPRESSO cohort. We also assessed the impact of baseline endoscopic and histology scores on time to IBD-related hospitalization.Results: We identified 5225 individuals with IBD comprising 11,051 endoscopic assessments in SWIBREG linked to a histopathology record in ESPRESSO. We created predictive models to calculate a SNOMED-based histology score which predicted the endoscopic score. Split-sample validated areas under the ROC curves for the score predicting a non-zero endoscopic score were 0.80 (0.78-0.81) in UC, 0.70 (0.68-0.72) in CD, and 0.76 (0.73-0.78) in IBD-U. In a subset of 2741 individuals with an initial IBD diagnosis and a corresponding record in ESPRESSO with an endoscopic assessment in SWIBREG, the baseline endoscopic and histology scores were associated with time to IBD-related hospitalization (endoscopy log-rank UC p<0.001, CD p=0.020, IBD-U p<0.001; histology log-rank UC p=0.018, CD p=0.960, IBD-U p=0.034).Conclusion: Histopathology data in ESPRESSO accurately predict endoscopic scores in SWIBREG. Baseline endoscopic and histologic scores were associated with time to IBD-related hospitalization, particularly in UC. The SNOMED-based histology score can be used as a measure of disease activity in future register-based IBD studies.
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| 2. |
- Everhov, Åsa H., et al.
(author)
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Inflammatory bowel disease and pancreatic cancer : a Scandinavian register-based cohort study 1969-2017
- 2020
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In: Alimentary Pharmacology and Therapeutics. - : John Wiley & Sons. - 0269-2813 .- 1365-2036. ; 52:1, s. 143-154
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Journal article (peer-reviewed)abstract
- Background: Patients with inflammatory bowel disease (IBD) have an increased risk of cancer.Aim: To assess the risk of pancreatic cancer in IBD compared to the general population.Methods: 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.Results: 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]).Conclusions: 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.
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| 3. |
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| 4. |
- Khalili, Hamed, et al.
(author)
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Mortality of Patients With Microscopic Colitis in Sweden
- 2020
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In: Clinical Gastroenterology and Hepatology. - : Elsevier. - 1542-3565 .- 1542-7714. ; 18:11, s. 2491-2499
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Journal article (peer-reviewed)abstract
- BACKGROUND & AIMS: Microscopic colitis is one of the most common causes of chronic diarrhea in older populations. We investigated all-cause and cause-specific mortality in patients with microscopic colitis.METHODS: We conducted a nationwide cohort study of all cases of microscopic colitis (n = 14,333) diagnosed from 1990 through 2017 in Sweden. Cases of microscopic colitis were identified using SNOMED codes from gastrointestinal histopathology reports collected from Sweden's 28 pathology departments. Each case of microscopic colitis was matched to 5 population comparators (n = 68,700). Mortality data were ascertained from Sweden's cause of death register. We used Cox proportional hazards modeling to estimate adjusted hazard ratios (aHRs) and 95% CIs.RESULTS: Through December of 2017, we confirmed 3014 deaths in patients with microscopic colitis (27.4/1000 person-years) and 12,534 deaths in matched population comparators (23.3/1000 person-years). This corresponded to a 10-year absolute risk difference of 3.4% (95% CI, 2.1%-4.6%) and an aHR of 1.17 (95% CI, 1.12-1.22). However, further adjustment of models for comorbidity burden reduced the relative risk of death for patients with microscopic colitis (aHR, 0.98; 95% CI, 0.94-1.02). In analyses of cause-specific death, microscopic colitis was associated with an increased risk of gastrointestinal-related death (aHR, 1.68; 95% CI, 1.38-2.05) and infection-related death (aHR, 1.42; 95% CI, 1.11-1.83), but not cancer-related death (aHR, 0.83; 95% CI, 0.76-0.91) or cardiovascular-related death (aHR, 1.02; 95% CI, 0.96-1.10).CONCLUSIONS: In a nationwide cohort study in Sweden, we found that patients with microscopic colitis were at increased risk of death. However, the increase appears to be related to higher burden of comorbidities in this population.
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| 5. |
- Liu, Bojing, et al.
(author)
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Vagotomy and subsequent risk of inflammatory bowel disease : a nationwide register-based matched cohort study
- 2020
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In: Alimentary Pharmacology and Therapeutics. - : John Wiley & Sons. - 0269-2813 .- 1365-2036. ; 51:11, s. 1022-1030
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Journal article (peer-reviewed)abstract
- Background: The vagus nerve provides essential parasympathetic innervation to the gastrointestinal system and is known to have anti-inflammatory properties.Aims: To explore the relationship between vagotomy and the risk of inflammatory bowel disease (IBD) and its major categories: Crohn's disease (CD) and ulcerative colitis (UC).Methods: A matched cohort comprising 15 637 patients undergoing vagotomy was identified through the Swedish Patient Register from 1964 to 2010. Each vagotomised patient was matched for birth year and gender with 40 nonvagotomised individuals on the date of vagotomy. We estimated hazard ratios (HRs) and 95% confidence intervals (CIs) for IBD using flexible parametric models adjusted for matching variables, year of vagotomy, birth country, chronic obstructive pulmonary disease and comorbidity index.Results: We observed 119 (0.8%) patients with vagotomy developed IBD compared to 3377 (0.5%) IBD cases in nonvagotomised individuals. The crude incidence of IBD (per 1000 person-years) was 0.38 for vagotomised patients and 0.25 for nonvagotomised individuals. We observed a time-dependent elevated risk of IBD associated with vagotomy, for instance, the HR (95% CI) was 1.80 (1.40-2.31) at year 5 and 1.49 (1.14-1.96) at year 10 post-vagotomy. The association appeared to be stronger for truncal than selective vagotomy and limited to CD (HR was 3.63 [1.94-6.80] for truncal and 2.06 [1.49-2.84] for selective vagotomy) but not UC (1.36 [0.71-2.62] for truncal and 1.25 [0.95-1.63] for selective vagotomy).Conclusions: We found a positive association between vagotomy and later IBD, particularly for CD. The finding indirectly underlines the beneficial role of the vagal tone in IBD.
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| 6. |
- Mouratidou, Natalia, et al.
(author)
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Adult height in patients with childhood-onset inflammatory bowel disease : a nationwide population-based cohort study
- 2020
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In: Alimentary Pharmacology and Therapeutics. - : John Wiley & Sons. - 0269-2813 .- 1365-2036. ; 51:8, s. 789-800
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Journal article (peer-reviewed)abstract
- Background: Growth retardation is well described in childhood-onset inflammatory bowel disease (IBD).Aims: To study if childhood-onset IBD is associated with reduced final adult height.Methods: We identified 4201 individuals diagnosed with childhood-onset IBD 1990-2014 (Crohn's disease: n = 1640; ulcerative colitis: n = 2201 and IBD-unclassified = 360) in the Swedish National Patient Register.Results: Patients with IBD attained a lower adult height compared to reference individuals (adjusted mean height difference [AMHD] -0.9 cm [95% CI -1.1 to -0.7]) and to their healthy siblings (AMHD -0.8 cm [-1.0 to -0.6]). Patients with Crohn's disease (CD) were slightly shorter than patients with ulcerative colitis (UC; -1.3 cm vs -0.6 cm). Lower adult height was more often seen in patients with pre-pubertal disease onset (AMHD -1.6 cm [-2.0 to -1.2]), and in patients with a more severe disease course (AMHD -1.9 cm, [-2.4 to -1.4]). Some 5.0% of CD and 4.3% of UC patients were classified as growth retarded vs 2.5% of matched reference individuals (OR 2.42 [95% CI 1.85-3.17] and 1.74 [1.36-2.22] respectively).Conclusion: Patients with childhood-onset IBD on average attain a slightly lower adult height than their healthy peers. Adult height was more reduced in patients with pre-pubertal onset of disease and in those with a more severe disease course.
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| 7. |
- Olén, Ola, et al.
(author)
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Colorectal cancer in Crohn's disease : a Scandinavian population-based cohort study
- 2020
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In: The Lancet Gastroenterology & Hepatology. - : Elsevier. - 2468-1253. ; 5:5, s. 475-484
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Journal article (peer-reviewed)abstract
- Background: 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.Methods: 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.Findings: 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.Interpretation: 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.
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| 8. |
- Olen, Ola, et al.
(author)
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Mortality in adult-onset and elderly-onset IBD : a nationwide register-based cohort study 1964-2014
- 2020
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In: Gut. - : BMJ Publishing Group Ltd. - 0017-5749 .- 1468-3288. ; 69:3, s. 453-461
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Journal article (peer-reviewed)abstract
- Objectives: To examine all-cause and cause-specific mortality in adult-onset and elderly-onset IBD and to describe time trends in mortality over the past 50 years.Design: Swedish nationwide register-based cohort study 1964-2014, comparing mortality in 82 718 incident IBD cases (inpatient and non-primary outpatient care) with 10 times as many matched general population reference individuals (n=801 180) using multivariable Cox regression to estimate HRs. Among patients with IBD, the number of participants with elderly-onset (>= 60 years) IBD was 17 873.Results: During 984 330 person-years of follow-up, 15 698/82 718 (19%) of all patients with IBD died (15.9/1000 person-years) compared with 121 095/801 180 (15.1%) of reference individuals, corresponding to an HR of 1.5 for IBD (95% CI=1.5 to 1.5 (HR=1.5; 95% CI=1.5 to 1.5 in elderly-onset IBD)) or one extra death each year per 263 patients. Mortality was increased specifically for UC (HR=1.4; 95% CI=1.4 to 1.5), Crohn's disease (HR=1.6; 95% CI=1.6 to 1.7) and IBD-unclasssified (HR=1.6; 95% CI=1.5 to 1.8). IBD was linked to increased rates of multiple causes of death, including cardiovascular disease (HR=1.3; 1.3 to 1.3), malignancy (HR=1.4; 1.4 to 1.5) and digestive disease (HR=5.2; 95% CI=4.9 to 5.5). Relative mortality during the first 5 years of follow-up decreased significantly over time. Incident cases of 2002-2014 had 2.3 years shorter mean estimated life span than matched comparators.Conclusions: Adult-onset and elderly-onset patients with UC, Crohn's disease and IBD-unclassified were all at increased risk of death. The increased mortality remained also after the introduction of biological therapies but has decreased over time.
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| 9. |
- Olén, Ola, et al.
(author)
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Colorectal cancer in ulcerative colitis : a Scandinavian population-based cohort study
- 2020
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In: The Lancet. - : Elsevier. - 0140-6736 .- 1474-547X. ; 395:10218, s. 123-131
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Journal article (peer-reviewed)abstract
- Background: 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.Methods: 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.Findings: 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<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).Interpretation: 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.
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