Publications by authors named "Anders Ekbom"

299 Publications

Periodontitis, assessed using periodontal treatment as a surrogate marker, has no association with a first myocardial infarction in a Swedish population.

J Periodontol 2021 Mar 11. Epub 2021 Mar 11.

Department of Dental Medicine, Karolinska Institutet, Huddinge, Sweden.

Background: Periodontitis is suggested to be associated with a risk of cardiovascular events. Using periodontal treatment recorded in Swedish national registries as a surrogate marker, we aimed to investigate whether periodontitis was associated with a first myocardial infarction.

Methods: This nationwide case-control study, with data from national registries, involved 51,880 individuals with a first myocardial infarction in 2011 to 2013 (index date) and 246,978 controls matched 5:1 for age, gender, and geographic area. Periodontal treatment in the 3 years preceding the index date was classified as (1) no dental treatment, (2) no periodontal treatment, (3) one or more supragingival curettages, or (4) one or more treatments with scaling/root planing and/or periodontal surgery. Annual frequencies of treatment with scaling/root planing and/or periodontal surgery were also calculated. In all analyses, conditional logistic regression analyses estimated ORs for myocardial infarction with 95% CIs, adjusted for matched variables, income, education, and diabetes.

Results: Although fewer cases than controls received treatment with scaling/root planing and/or periodontal surgery (19.2% versus 19.8%, P < 0.001), annual frequencies for cases were higher. We found no association of scaling/root planing and/or periodontal surgery with a first myocardial infarction (OR = 1.02; 95% CI: 1.00, 1.05). We did observe a non-significant trend, however, between risk of a first myocardial infarction and a high frequency of scaling/root planing and/or periodontal surgery (OR 1.14; 95% CI: 1.00, 1.29).

Conclusion: In the contemporary Swedish nationwide setting, no association between a first myocardial infarction and periodontitis, assessed as periodontal treatment, was found.
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http://dx.doi.org/10.1002/JPER.20-0758DOI Listing
March 2021

Hepatobiliary Cancer Risk in Patients with Inflammatory Bowel Disease: A Scandinavian Population-Based Cohort Study.

Cancer Epidemiol Biomarkers Prev 2021 05 24;30(5):886-894. Epub 2021 Feb 24.

Department of Clinical Epidemiology, Aarhus University Hospital, Aarhus, Denmark.

Background: Inflammatory bowel disease (IBD) has been associated with hepatobiliary cancer, but existing evidence is poor. We evaluated risk of death from hepatocellular carcinoma (HCC), intrahepatic cholangiocarcinoma (ICC), and extrahepatic cholangiocarcinoma (ECC) among patients with IBD.

Methods: This Swedish/Danish population-based cohort study (1969-2017) followed patients with IBD and 1:10 matched population comparators from their diagnosis/match date until death, emigration, or end of follow-up.

Results: Among the 97,496 patients with ulcerative colitis/963,026 comparators, we found 66/390 HCC-deaths, 120/173 ICC-deaths, and 91/220 ECC-deaths (median follow-up 10 years); the 10-year-mortality was 0.5‰ (per mille) for HCC, 0.6‰ for ICC, and 0.4‰ for ECC, which decreased to 0.3‰, 0.4‰, and 0.2‰, respectively, in 2003-2017. Overall hazard ratios (HR) were 1.83 [95% confidence interval (CI), 1.41-2.38] for HCC-, 7.33 (95% CI, 5.81-9.25) for ICC-, and 4.46 (95% CI, 3.49-5.70) for ECC-deaths. A total of 22/66 HCC-deaths, 87/120 ICC-deaths, and 55/91 ECC-deaths occurred among patients with ulcerative colitis with primary sclerosing cholangitis (PSC), corresponding to 10-year-mortality of 6.7‰, 26.2‰, and 17.2‰, respectively. Among 47,399 patients with Crohn's disease (median follow-up 11 years), 10-year-mortality from HCC ( = 28), ICC ( = 28), and ECC ( = 24) were 0.3‰, 0.1‰, and 0.3‰, respectively, and corresponding HRs were 1.96 (95% CI, 1.31-2.93), 3.33 (95% CI, 2.19-5.09), and 3.10 (95% CI, 1.97-4.87). One of 28 HCC-deaths, 14/28 ICC-deaths (10-year-mortality 19‰), and 12/24 ECC-deaths (10-year-mortality 14‰) occurred after PSC.

Conclusions: Risk of HCC-, ICC-, and ECC-deaths was low in patients with IBD and decreased over time. However, a large proportion of deaths occurred after PSC.

Impact: Guidelines on specific surveillance strategies for patients with IBD with PSC, but not those without PSC, are needed.
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http://dx.doi.org/10.1158/1055-9965.EPI-20-1241DOI Listing
May 2021

Maternal health, in-utero, and perinatal exposures and risk of thyroid cancer in offspring: a Nordic population-based nested case-control study.

Lancet Diabetes Endocrinol 2021 02 18;9(2):94-105. Epub 2020 Dec 18.

Department of Global Public Health and Primary Care, University of Bergen, Bergen, Norway; Cancer Registry of Norway, Oslo, Norway.

Background: Thyroid cancer tends to be diagnosed at a younger age (median age 51 years) compared with most other malignancies (such as breast cancer [62 years] or lung cancer [71 years]). The incidence of thyroid cancer is higher in women than men diagnosed from early adolescence. However, few in-utero and early life risk exposures associated with increased risk of thyroid cancer have been identified.

Methods: In this population-based nested case-control study we used registry data from four Nordic countries to assess thyroid cancer risk in offspring in relation to maternal medical history, pregnancy complications, and birth characteristics. Patient with thyroid cancer (cases) were individuals born and subsequently diagnosed with first primary thyroid cancer from 1973 to 2013 in Denmark, 1987 to 2014 in Finland, 1967 to 2015 in Norway, or 1973 to 2014 in Sweden. Each case was matched with up to ten individuals without thyroid cancer (controls) based on birth year, sex, country, and county of birth. Cases and matched controls with a previous diagnosis of any cancer, other than non-melanoma skin cancer, at the time of thyroid cancer diagnosis were excluded. Cases and matched controls had to reside in the country of birth at the time of thyroid cancer diagnosis. Conditional logistic regression models were used to calculate odds ratios (ORs) with 95% CIs.

Results: Of the 2437 cases, 1967 (81·4%) had papillary carcinomas, 1880 (77·1%) were women, and 1384 (56·7%) were diagnosed before age 30 years (range 0-48). Higher birth weight (OR per kg 1·14 [95% CI 1·05-1·23]) and congenital hypothyroidism (4·55 [1·58-13·08]); maternal diabetes before pregnancy (OR 1·69 [0·98-2·93]) and postpartum haemorrhage (OR 1·28 [1·06-1·55]); and (from registry data in Denmark) maternal hypothyroidism (18·12 [10·52-31·20]), hyperthyroidism (11·91 [6·77-20·94]), goiter (67·36 [39·89-113·76]), and benign thyroid neoplasms (22·50 [6·93-73·06]) were each associated with an increased risk of thyroid cancer in offspring.

Interpretation: In-utero exposures, particularly those related to maternal thyroid disorders, might have a long-term influence on thyroid cancer risk in offspring.

Funding: Intramural Research Program of the National Cancer Institute (National Institutes of Health).
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http://dx.doi.org/10.1016/S2213-8587(20)30399-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7875310PMC
February 2021

Cancer risk in individuals with major birth defects: large Nordic population based case-control study among children, adolescents, and adults.

BMJ 2020 12 2;371:m4060. Epub 2020 Dec 2.

Department of Global Public Health and Primary Care, University of Bergen, Bergen, Norway.

Objective: To examine associations between birth defects and cancer from birth into adulthood.

Design: Population based nested case-control study.

Setting: Nationwide health registries in Denmark, Finland, Norway, and Sweden.

Participants: 62 295 cancer cases (0-46 years) and 724 542 frequency matched controls (matched on country and birth year), born between 1967 and 2014.

Main Outcome Measures: Relative risk of cancer in relation to major birth defects, estimated as odds ratios with 99% confidence intervals from logistic regression models.

Results: Altogether, 3.5% (2160/62 295) of cases and 2.2% (15 826/724 542) of controls were born with major birth defects. The odds ratio of cancer for people with major birth defects compared with those without was 1.74 (99% confidence interval 1.63 to 1.84). For individuals with non-chromosomal birth defects, the odds ratio of cancer was 1.54 (1.44 to 1.64); for those with chromosomal anomalies, the odds ratio was 5.53 (4.67 to 6.54). Many structural birth defects were associated with later cancer in the same organ system or anatomical location, such as defects of the eye, nervous system, and urinary organs. The odds ratio of cancer increased with number of defects and decreased with age, for both non-chromosomal and chromosomal anomalies. The odds ratio of cancer in people with any non-chromosomal birth defect was lower in adults (≥20 years: 1.21, 1.09 to 1.33) than in adolescents (15-19 years: 1.58, 1.31 to 1.90) and children (0-14 years: 2.03, 1.85 to 2.23). The relative overall cancer risk among adults with chromosomal anomalies was markedly reduced from 11.3 (9.35 to 13.8) in children to 1.50 (1.01 to 2.24). Among adults, skeletal dysplasia (odds ratio 3.54, 1.54 to 8.15), nervous system defects (1.76, 1.16 to 2.65), chromosomal anomalies (1.50, 1.01 to 2.24), genital organs defects (1.43, 1.14 to 1.78), and congenital heart defects (1.28, 1.02 to 1.59) were associated with overall cancer risk.

Conclusions: The increased risk of cancer in individuals with birth defects persisted into adulthood, both for non-chromosomal and chromosomal anomalies. Further studies on the molecular mechanisms involved are warranted.
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http://dx.doi.org/10.1136/bmj.m4060DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7708828PMC
December 2020

Reply: Survival in Crohn's disease-associated small bowel adenocarcinoma.

Gut 2021 May 1;70(5):998. Epub 2020 Sep 1.

Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.

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http://dx.doi.org/10.1136/gutjnl-2020-322450DOI Listing
May 2021

Paediatric infections in the first 3 years of life after maternal anti-TNF treatment during pregnancy.

Aliment Pharmacol Ther 2020 09 24;52(5):843-854. Epub 2020 Jul 24.

Stockholm, Sweden.

Background: Most anti-tumour necrosis factor (anti-TNF) agents are transferred across the placenta and may increase paediatric susceptibility to infections.

Aims: To assess the risk of paediatric infections after maternal anti-TNF treatment.

Methods: Population-based cohort study in Denmark, Finland and Sweden 2006-2013 in which 1027 children born to women with rheumatoid arthritis, psoriasis, psoriatic arthritis, ankylosing spondylitis or inflammatory bowel disease, treated with anti-TNF, and 9346 children to women with non-biologic systemic treatment, were compared to 1 617 886 children of the general population. Children were followed for 3 years.

Results: Adjusted by maternal age, parity, smoking, body mass index, country and calendar year, the incidence rate ratios with 95% confidence interval (CI) for hospital admissions for infection in the first year were 1.43 (1.23-1.67) for anti-TNF and 1.14 (1.07-1.21) for non-biologic systemic treatment, and 1.29 (1.11-1.50) and 1.09 (1.02-1.15), respectively, when additionally adjusting for adverse birth outcomes. There was a slight increase in antibiotic prescriptions in the second year for anti-TNF, 1.19 (1.11-1.29), and for non-biologic systemic treatment, 1.10 (1.07-1.13). There was no difference among anti-TNF agents, treatment in the third trimester, or between mono/combination therapy with non-biologic systemic treatment.

Conclusions: Both anti-TNF and non-biologic systemic treatment were associated with an increased risk of paediatric infections. However, reassuringly, the increased risks were present regardless of treatment in the third trimester, or with combination treatment, and were not persistent during the first 3 years of life. Our findings may indicate a true risk, but could also be due to unadjusted confounding by disease severity and healthcare-seeking behaviour. This may in turn shift the risk-benefit equation towards continuation of treatment even in the third trimester.
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http://dx.doi.org/10.1111/apt.15971DOI Listing
September 2020

Postcolonoscopy Colorectal Cancer in Sweden From 2003 to 2012: Survival, Tumor Characteristics, and Risk Factors.

Clin Gastroenterol Hepatol 2020 11 15;18(12):2724-2733.e3. Epub 2020 Jun 15.

Department of Medicine, Karolinska Institutet, Solna (MedS), Stockholm, Sweden.

Background & Aims: The rate of postcolonoscopy colorectal cancer (PCCRC) is a measure of colonoscopy quality, but there are conflicting results from studies of survival times of patients with PCCRC. We assessed survival times of patients with PCCRC and characterized the microscopic and macroscopic features of postcolonoscopy colorectal tumors.

Methods: We performed a population-based cohort study using data from a database in Sweden, on 458,937 colonoscopies (54.0% women) performed from 2003 through 2012. Rates of colorectal cancer within 3 years of a colonoscopy were calculated based on the World Endoscopy Organization guidelines. Risk factors were evaluated using Poisson regression analysis. We used Cox regression models and Kaplan-Meier analyses, stratified by sex, to assess conditional survival. Logistic regression models were used to evaluate features of postcolonoscopy colorectal tumors, including stage location (right, left, or rectum) differentiation grade (high or low), synchronous tumors, perineural growth, resection margins, and mucinous and vessel characteristics.

Results: Within 36 months after a colonoscopy, there were 19,184 individuals who had received a diagnosis of CRC; 1384 of these were PCCRCs (7.2%). The proportion of individuals with PCCRC decreased from 9.4% in 2003 to 6.1% in 2012. The largest risk factors for PCCRC were a prior diagnosis of CRC (relative risk [RR], 3.31; 95% CI, 2.71-4.04), ulcerative colitis (RR, 5.44; 95% CI, 4.75-6.23), Crohn's disease (RR, 3.81; 95% CI, 2.98-4.87), and prior polypectomy (RR, 2.32; 95% CI, 1.97-2.72). Individuals with PCCRCs had shorter survival times than individuals with CRCs detected during the index colonoscopy. Multivariate hazard ratios for PCCRC were 2.75 for men (95% CI, 2.21-3.42) and 2.00 for women (95% CI, 1.59-2.52), respectively. Individuals with left-side PCCRC had shorter survival times than patients with CRC detected during the index colonoscopy. Postcolonoscopy colorectal tumors had increased odds of low differentiation grade (odds ratio, 1.27; 95% CI, 1.09-1.49) compared with colorectal tumors detected during the index colonoscopy.

Conclusions: In an analysis of colonoscopies in Sweden, the rate of PCCRCs decreased from 9.4% in 2003 to 6.1% in 2012. Diseases that require surveillance (such as prior colorectal neoplasms and inflammatory bowel diseases) are the largest risk factors for PCCRC. Patients with PCCRC have shorter survival times than patients with CRC detected during their initial colonoscopy-especially women and patients with left-side tumors.
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http://dx.doi.org/10.1016/j.cgh.2020.06.010DOI Listing
November 2020

Inflammatory bowel disease and risk of small bowel cancer: a binational population-based cohort study from Denmark and Sweden.

Gut 2021 02 30;70(2):297-308. Epub 2020 May 30.

Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.

Objective: 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).

Design: 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).

Results: 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).

Conclusion: SBC and death from SBC were more common in patients with IBD, particularly among patients with CD, although absolute risks were low.
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http://dx.doi.org/10.1136/gutjnl-2020-320945DOI Listing
February 2021

Beta-adrenergic receptor blockers and liver cancer mortality in a national cohort of hepatocellular carcinoma patients.

Scand J Gastroenterol 2020 May 15;55(5):597-605. Epub 2020 May 15.

Clinical Epidemiology and Biostatistics, School of Medical Sciences, Örebro University, Örebro, Sweden.

β-adrenergic signaling has been implicated in the pathology of hepatocellular carcinoma (HCC), but the evidence from clinical studies is limited. In this national population-based cohort study, we investigated the possible association of β-adrenergic receptor blockers and cancer-specific mortality among patients with primary HCC diagnosed in Sweden between 2006 and 2014. Patients were identified from the Swedish Cancer Register ( = 2104) and followed until 31 December 2015. We used Cox regression to evaluate the association of β-blockers dispensed within 90 days prior to cancer diagnosis, ascertained from the national Prescribed Drug Register, with liver cancer mortality identified from the Cause of Death Register, while controlling for socio-demographic factors, tumor characteristics, comorbidity, other medications and treatment procedures. Over a median follow-up of 9.9 months, 1601 patients died (of whom 1309 from liver cancer). Compared with non-use, β-blocker use at cancer diagnosis [ = 714 (predominantly prevalent use, 93%)] was associated with lower liver cancer mortality [0.82 (0.72-0.94); = .005]. Statistically significant associations were observed for non-selective [0.71 (0.55-0.91); = .006], β1-receptor selective [0.86 [0.75-1.00); = .049] and lipophilic [0.78 (0.67-0.90); = .001] β-blockers. No association was observed for hydrophilic β-blockers [1.01 (0.80-1.28); = .906] or other antihypertensive medications. Further analysis suggested that the observed lower liver cancer mortality rate was limited to patients with localized disease at diagnosis [0.82 (0.67-1.01); = .062]. β-blocker use was associated with lower liver cancer mortality rate in this national cohort of patients with HCC. A higher-magnitude inverse association was observed in relation to non-selective β-blocker use.
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http://dx.doi.org/10.1080/00365521.2020.1762919DOI Listing
May 2020

Inflammatory bowel disease and pancreatic cancer: a Scandinavian register-based cohort study 1969-2017.

Aliment Pharmacol Ther 2020 07 15;52(1):143-154. Epub 2020 May 15.

Stockholm, Sweden.

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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http://dx.doi.org/10.1111/apt.15785DOI Listing
July 2020

Pregnancy-related risk factors for sex cord-stromal tumours and germ cell tumours in parous women: a registry-based study.

Br J Cancer 2020 07 27;123(1):161-166. Epub 2020 Apr 27.

Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden.

Background: Non-epithelial ovarian cancers are divided into sex cord-stromal tumours (SCSTs) and germ cell tumours (GCTs). Whereas parity and other pregnancy-related factors are protective for epithelial ovarian cancer, their associations with SCSTs and GCTs remains unclear.

Methods: Using data from the medical birth registries from Denmark, Finland, Norway and Sweden, we compared all parous women with a diagnosis of SCSTs (n = 420) or GCTs (n = 345) 1970-2013 with up to 10 parous controls (SCSTs n = 4041; GCTs n = 2942) matched on the cases' birth year and country. We used conditional logistic regression to estimate odds ratios (ORs) with 95% confidence intervals (CIs) of associations between pregnancy-related factors and SCSTs and GCTs.

Results: The risk of SCSTs, but not GCTs, decreased with higher age at last birth [≥40 versus <25 years: OR 0.48 (95% CI 0.23-0.98)]. The risk of SCSTs (but not GCTs) also decreased with shorter time since last birth. Number of births, preterm birth, preeclampsia, and offspring size were not associated with risk of SCSTs or GCTs.

Conclusions: We found a decreased risk of SCSTs with higher age at last birth and shorter time since last birth. The risk of SCSTs (but not GCTs) may be influenced by the woman's reproductive history.
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http://dx.doi.org/10.1038/s41416-020-0849-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7340776PMC
July 2020

Vagotomy and subsequent risk of inflammatory bowel disease: a nationwide register-based matched cohort study.

Aliment Pharmacol Ther 2020 06 22;51(11):1022-1030. Epub 2020 Apr 22.

Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.

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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http://dx.doi.org/10.1111/apt.15715DOI Listing
June 2020

Incidence of pulmonary and venous thromboembolism in pregnancies after in vitro fertilization with fresh respectively frozen-thawed embryo transfer: Nationwide cohort study.

J Thromb Haemost 2020 08 11;18(8):1965-1973. Epub 2020 May 11.

Department of Clinical Sciences, Danderyd Hospital, Karolinska Institutet, Stockholm, Sweden.

Background: The assisted reproductive technique in vitro fertilization (IVF) is associated with an increased risk of venous thromboembolism (VTE) and pulmonary embolism (PE) during the first trimester.

Objectives: To compare the incidence of VTE and PE during the first trimester of IVF pregnancies using fresh or frozen-thawed embryo transfer to that during natural pregnancies.

Patient/methods: Nationwide Swedish registry-based cohort study of women who gave birth (n = 902 891) at the age of 15-50 years to their first child from the 1st of January 1992 until the 31st of December 2012. Exposure groups were IVF with fresh respectively frozen-thawed embryo transfer. Incidences of VTE and PE were calculated, and time-varying hazard ratios estimated for all trimesters after fresh respectively frozen-thawed embryo transfer IVF and compared to natural conception.

Results And Conclusion: Women giving birth after fresh embryo transfer IVF had a more than eightfold increased incidence of venous thromboembolism (hazard ratio [HR] 8.96, 95% CI 6.33 to 12.67) and pulmonary embolism during the first trimester, (HR 8.69, 95% CI 3.83 to 19.71) compared to women giving birth after natural conception. The incidence of VTE in women giving birth after frozen-thawed embryo transfer was not increased during the first trimester. To conclude, fresh embryo transfer IVF was associated with a significantly increased incidence of VTE and PE during the first trimester. These results suggest that frozen-thawed embryo transfer could be a preferred method of IVF with a minimised maternal risk.
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http://dx.doi.org/10.1111/jth.14840DOI Listing
August 2020

Rising incidence of acute pancreatitis in Sweden: National estimates and trends between 1990 and 2013.

United European Gastroenterol J 2020 05 13;8(4):472-480. Epub 2020 Mar 13.

Clinical Epidemiology Division, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden.

Background: Recent reports from western countries have indicated an increased incidence and a decreased mortality in acute pancreatitis. However, the incidence assessment has often been hampered by the inclusion of both first-time and recurrent episodes of acute pancreatitis.

Methods: In this retrospective cohort study, all Swedish residents hospitalized with a first-time episode of acute pancreatitis between 1990 and 2013 were identified using national registers. Sex- and age-standardized incidence rates per 100,000 individuals and year were calculated, as were annual percent changes (APC) from joinpoint regression models.

Results: Overall, between 1990 and 2013, 66,131 individuals had a first-time episode of acute pancreatitis in Sweden. Comparing the first five years (1990-1994) to the last four years (2010-2013) of the study period, the overall incidence of acute pancreatitis increased from 25.2 (95% confidence interval (CI): 24.1, 26.3) to 38.3 (95% CI: 37.0, 39.5) cases per 100,000 individuals and year. An increase in incidence was observed irrespective of the subtypes of acute pancreatitis as well as the sex and age of the patients. Although the incidence of complicated acute pancreatitis declined in both men and women between 1990 and 2004, it started to increase in both sexes (APC 3.0; 95% CI: 0.5, 5.5 in men; APC 5.4; 95% CI: 2.6, 8.2 in women) from 2005 onwards.

Conclusion: Based on nationwide data, the incidence of first-time acute pancreatitis has increased in Sweden over a period of 24 years. The incidence of disease-related complications has also been on the rise during the past few years, after declining for more than 15 years before that.
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http://dx.doi.org/10.1177/2050640620913737DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7226686PMC
May 2020

Birthweight and all-cause mortality after childhood and adolescent leukemia: a cohort of children with leukemia from Denmark, Norway, Sweden, and Washington State.

Acta Oncol 2020 Aug 14;59(8):949-958. Epub 2020 Mar 14.

Department of Clinical Epidemiology, Aarhus University Hospital, Aarhus, Denmark.

High birthweight may predispose children to acute lymphoid leukemia, whereas low birthweight is associated with childhood morbidity and mortality. Low and high birthweight have been inconsistently associated with mortality in children with leukemia. In a cohort of childhood and adolescent leukemia (0-19 years) patients from registries in Denmark, Norway, Sweden, and Washington State in the United States (1967-2015), five-year all-cause mortality was assessed by birthweight and other measures of fetal growth using the cumulative incidence function and Cox regression with adjustment for sex, diagnosis year, country, the presence of Down's syndrome or other malformations, and type of leukemia. Among 7148 children and adolescents with leukemia (55% male), 4.6% were low (<2500 g) and 19% were high (≥4000 g) birthweight. Compared with average weight, hazard ratios (HRs) of death associated with low birthweight varied by age at leukemia diagnosis: 1.5 (95% confidence interval (CI): 0.7, 3.2) for patients 0-1 year old, 1.6 (95% CI: 1.0, 2.6) for >1-2 years old; 1.0 (95% CI: 0.6, 1.5) for 3-8 years old; 1.0 (95% CI: 0.6, 1.8) for 9-13 years old; and 1.2 (95% CI: 0.7, 2.1) for 14-19 years old, and were similar for size for gestational age and Ponderal index. In analyses restricted to children born full term (37-41 weeks of gestation), results were only slightly attenuated but risk was markedly increased for infants aged ≤1 year (HR for low birthweight = 3.2, 95% CI: 1.2, 8.8). This cohort study does not suggest that low birthweight or SGA is associated with increased five-year all-cause mortality risk among children with any type of childhood leukemia or acute lymphoblastic leukemia, specifically, beyond infancy.
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http://dx.doi.org/10.1080/0284186X.2020.1738546DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7392817PMC
August 2020

Adult height in patients with childhood-onset inflammatory bowel disease: a nationwide population-based cohort study.

Aliment Pharmacol Ther 2020 04 4;51(8):789-800. Epub 2020 Mar 4.

Division of Clinical Epidemiology, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden.

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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http://dx.doi.org/10.1111/apt.15667DOI Listing
April 2020

Colorectal cancer in Crohn's disease: a Scandinavian population-based cohort study.

Lancet Gastroenterol Hepatol 2020 05 14;5(5):475-484. Epub 2020 Feb 14.

Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden; Department of Pediatrics, Faculty of Medicine and Health, Örebro University, Örebro, Sweden; Division of Epidemiology and Public Health, School of Medicine, University of Nottingham, Nottingham, UK; Department of Medicine, Columbia University College of Physicians and Surgeons, New York, NY, USA.

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.

Funding: Swedish Medical Society, Karolinska Institutet, Regional Agreement on Medical Training and Clinical Research between Stockholm County Council and Karolinska Institutet (ALF), Forte Foundation, Swedish Cancer Foundation, and Independent Research Fund Denmark.
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http://dx.doi.org/10.1016/S2468-1253(20)30005-4DOI Listing
May 2020

Anti-TNF treatment during pregnancy and birth outcomes: A population-based study from Denmark, Finland, and Sweden.

Pharmacoepidemiol Drug Saf 2020 03 4;29(3):316-327. Epub 2020 Feb 4.

Clinical Epidemiology Division, Department of Medicine Solna, Karolinska institutet, Stockholm, Sweden.

Purpose: To study the risk of preterm birth, caesarean section, and small for gestational age after anti-tumor necrosis factor agent treatment (anti-TNF) in pregnancy.

Methods: Population-based study including women with inflammatory bowel disease, rheumatoid arthritis, ankylosing spondylitis, psoriatic arthritis, and psoriasis, and their infants born 2006 to 2013 from the national health registers in Denmark, Finland, and Sweden. Women treated with anti-TNF were compared with women with nonbiologic systemic treatment. Adalimumab, etanercept, and infliximab were compared pairwise. Continuation of treatment in early pregnancy was compared with discontinuation. Odds ratios with 95% confidence intervals were calculated in logistic regression models adjusted for country and maternal characteristics.

Results: Among 1 633 909 births, 1027 infants were to women treated with anti-TNF and 9399 to women with nonbiologic systemic treatment. Compared with non-biologic systemic treatment, women with anti-TNF treatment had a higher risk of preterm birth, odds ratio 1.61 (1.29-2.02) and caesarean section, 1.57 (1.35-1.82). The odds ratio for small for gestational age was 1.36 (0.96-1.92). In pairwise comparisons, infliximab was associated with a higher risk of severely small for gestational age for inflammatory joint and skin diseases but not for inflammatory bowel disease. Discontinuation of anti-TNF had opposite effects on preterm birth for inflammatory bowel disease and inflammatory joint and skin diseases.

Conclusions: Anti-TNF agents were associated with increased risks of preterm birth, caesarean section, and small for gestational age. However, the diverse findings across disease groups may indicate an association related to the underlying disease activity, rather than to agent-specific effects.
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http://dx.doi.org/10.1002/pds.4930DOI Listing
March 2020

Colorectal cancer in ulcerative colitis: a Scandinavian population-based cohort study.

Lancet 2020 01;395(10218):123-131

Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden; Department of Pediatrics, Orebro University Hospital, Orebro, Sweden; Division of Epidemiology and Public Health, School of Medicine, University of Nottingham, Nottingham, UK; Department of Medicine, Columbia University College of Physicians and Surgeons, New York, NY, USA.

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.

Funding: The Swedish Medical Society, Karolinska Institutet, Stockholm County Council, Swedish Research Council, Swedish Foundation for Strategic Research, Independent Research Fund Denmark, Forte Foundation, Swedish Cancer Foundation.
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http://dx.doi.org/10.1016/S0140-6736(19)32545-0DOI Listing
January 2020

Beta-Blocker Use and Lung Cancer Mortality in a Nationwide Cohort Study of Patients with Primary Non-Small Cell Lung Cancer.

Cancer Epidemiol Biomarkers Prev 2020 01 22;29(1):119-126. Epub 2019 Oct 22.

Clinical Epidemiology and Biostatistics, School of Medical Sciences, Örebro University, Örebro, Sweden.

Background: β-Adrenergic receptor blockers have been associated with improved survival among patients with different types of malignancies, but available data for patients with non-small cell lung cancer (NSCLC) are contradictory and limited to small hospital-based studies. We therefore aimed to investigate whether β-blocker use at the time of cancer diagnosis is associated with lung cancer mortality in the largest general population-based cohort of patients with NSCLC to date.

Methods: For this retrospectively defined nationwide cohort study, we used prospectively collected data from Swedish population and health registers. Through the Swedish Cancer Register, we identified 18,429 patients diagnosed with a primary NSCLC between 2006 and 2014 with follow-up to 2015. Cox regression was used to estimate the association between β-blocker use at time of cancer diagnosis ascertained from the Prescribed Drug Register and cancer-specific mortality identified from the Cause of Death Register.

Results: Over a median follow-up of 10.2 months, 14,994 patients died (including 13,398 from lung cancer). Compared with nonuse, β-blocker use (predominantly prevalent use, 93%) was not associated with lung cancer mortality [HR (95% confidence interval): 1.01 (0.97-1.06)]. However, the possibility that diverging associations for specific β-blockers and some histopathologic subtypes exist cannot be excluded.

Conclusions: In this nationwide cohort of patients with NSCLC, β-blocker use was not associated with lung cancer mortality when assessed in aggregate in the total cohort, but evidence for some β-blockers is less conclusive.

Impact: Our results do not indicate that β-blocker use at lung cancer diagnosis reduces the cancer-specific mortality rate in patients with NSCLC.
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http://dx.doi.org/10.1158/1055-9965.EPI-19-0710DOI Listing
January 2020

Associations of pregnancy-related factors and birth characteristics with risk of endometrial cancer: A Nordic population-based case-control study.

Int J Cancer 2020 03 20;146(6):1523-1531. Epub 2019 Jun 20.

Cancer Registry of Norway, Oslo, Norway.

Many pregnancy-related factors are associated with reduced endometrial cancer risk. However, it remains unclear whether pregnancy-related complications (e.g., hypertensive conditions) are associated with risk and whether these associations vary by endometrial cancer subtype. Thus, we evaluated the risk of endometrial cancer, overall and by subtype, in relation to pregnancy-related factors, pregnancy complications and birth characteristics. Utilizing population-based register data from four Nordic countries, we conducted a nested case-control analysis of endometrial cancer risk. We included 10,924 endometrial cancer cases and up to 10 matched controls per case. Odds ratios (ORs) with 95% confidence intervals (CIs) were derived from unconditional logistic regression models. We further evaluated associations by individual histology (i.e., endometrioid, serous, etc.) or, for rare exposures (e.g., pregnancy complications), by dualistic type (Type I [n = 10,343] and Type II [n = 581]). Preexisting and pregnancy-related hypertensive conditions were associated with increased endometrial cancer risk (OR [95% CI]: preexisting hypertension 1.88 [1.39-2.55]; gestational hypertension 1.47 [1.33-1.63]; preeclampsia 1.43 [1.30-1.58]), with consistent associations across dualistic type. Increasing number of pregnancies (≥4 vs. 1 birth: 0.64 [0.59-0.69]) and shorter time since last birth (<10 vs. ≥30 years: 0.34 [0.29-0.40]) were associated with reduced endometrial cancer risk, with consistent associations across most subtypes. Our findings support the role for both hormonal exposures and cell clearance as well as immunologic/inflammatory etiologies for endometrial cancer. This research supports studying endometrial hyperplasia, a precursor condition of endometrial cancer, in the context of pregnancy-related exposures, as this may provide insight into the mechanisms by which pregnancy affects subsequent cancer risk.
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http://dx.doi.org/10.1002/ijc.32494DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6898733PMC
March 2020

Mortality in adult-onset and elderly-onset IBD: a nationwide register-based cohort study 1964-2014.

Gut 2020 03 15;69(3):453-461. Epub 2019 May 15.

Department of Pediatrics, Örebro University Hospital, Örebro, Sweden.

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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http://dx.doi.org/10.1136/gutjnl-2018-317572DOI Listing
March 2020

Survival among solid organ transplant recipients diagnosed with cancer compared to nontransplanted cancer patients-A nationwide study.

Int J Cancer 2020 02 11;146(3):682-691. Epub 2019 Apr 11.

Division of Clinical Epidemiology, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden.

Solid organ transplant recipients (OTRs) have an increased cancer risk but their survival once diagnosed with cancer has seldom been assessed. We therefore investigated cancer-specific survival among OTRs with a wide range of cancer forms nationally in Sweden. The study included 2,143 OTRs with cancer, and 946,089 nontransplanted cancer patients diagnosed 1992-2013. Hazard ratios (HR) and 95% confidence intervals (CI) were estimated using Cox regression models adjusted for age, sex and calendar year. Median follow-up was 3.1 (range 0-22) years. Overall, OTRs diagnosed with any cancer had a 35% higher rate of cancer death compared to nontransplanted cancer patients (HR: 1.35, 95% CI: 1.24-1.47). Specifically, higher rates of cancer-specific death were observed among OTRs diagnosed with Hodgkin lymphoma (HR: 15.0, 95% CI: 5.56-40.6), high-grade non-Hodgkin lymphoma (HR: 2.68, 95% CI: 1.90-3.77), malignant melanoma (HR: 2.80, 95% CI: 1.74-4.52) and urothelial (HR: 2.56, 95% CI: 1.65-3.97), breast (HR: 2.12, 95% CI: 1.38-3.25), head/neck (HR: 1.55, 95% CI: 1.02-2.36) and colorectal (HR: 1.42, 95% CI: 1.07-1.88) cancer. The worse outcomes were not explained by differences in distribution of cancer stage or histologic subtypes. For other common cancer forms such as prostate, lung and kidney cancer, the prognosis was similar to that in nontransplanted cancer patients. In conclusion, several but not all types of posttransplantation cancer diagnoses are associated with worse outcomes than in the general population. Reasons for this should be further explored to optimize posttransplantation cancer management.
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http://dx.doi.org/10.1002/ijc.32299DOI Listing
February 2020

Effects of Childhood-onset Inflammatory Bowel Disease on School Performance: A Nationwide Population-based Cohort Study Using Swedish Health and Educational Registers.

Inflamm Bowel Dis 2019 09;25(10):1663-1673

Sachs' Children and Youth Hospital, South General Hospital, Stockholm, Sweden.

Background: Childhood-onset inflammatory bowel disease (IBD) might negatively impact academic school performance. We conducted a nationwide study to examine the association between childhood-onset IBD and school results.

Methods: Our study population was selected from Swedish health registers. In the National Patient Register (1990 to 2013), we identified 2827 children with IBD: Crohn's disease (CD), n = 1207, and ulcerative colitis (UC), n = 1370. Patients were matched with 10 reference individuals by age, sex, birth year, and place of residence (n = 28,235). Final compulsory school grades (0 to 320 grade points) and qualification for high school (yes or no) were obtained through the National School Register. Regression models controlling for socioeconomic factors were used to analyze the association of IBD with school performance.

Results: Children with IBD had a lower final grade point average (adjusted mean grade difference [AMGD] -4.9, 95% confidence interval [CI] -7.1 to -2.6) but not a significantly higher risk to not qualify for high school (odds ratio [OR] 1.14, CI 0.99-1.31). The results were similar in children with UC (AMGD -5.5, CI -8.7 to -2.3) and CD (AMGD -4.7, CI -8.2 to -1.2). Underperformance was more common in subsets of IBD children characterized by markers associated with long-standing active disease (eg, >30 inpatient days [AMGD-18.1, CI -25.8 to -10.4]).

Conclusion: Most children with IBD achieve comparable results in the final year of compulsory school as their healthy peers. Care should be improved for the subgroup of children for which IBD has a stronger negative impact on school performance.
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http://dx.doi.org/10.1093/ibd/izz040DOI Listing
September 2019

Comorbidity and long-term outcome in patients with congenital heart block and their siblings exposed to Ro/SSA autoantibodies in utero.

Ann Rheum Dis 2019 05 26;78(5):696-703. Epub 2019 Feb 26.

Department of Medicine, Karolinska Institutet, Stockholm, Sweden

Objective: Congenital heart block (CHB) may develop in fetuses of Ro/SSA autoantibody-positive women. Given the rarity of CHB, information on comorbidity and complications later in life is difficult to systematically collect for large groups of patients. We therefore used nation-wide healthcare registers to investigate comorbidity and outcomes in patients with CHB and their siblings.

Methods: Data from patients with CHB (n= 119) and their siblings (n= 128), all born to anti-Ro/SSA-positive mothers, and from matched healthy controls (n= 1,190) and their siblings (n= 1,071), were retrieved from the Swedish National Patient Register. Analyses were performed by Cox proportional hazard modelling.

Results: Individuals with CHB had a significantly increased risk of cardiovascular comorbidity, with cardiomyopathy and/or heart failure observed in 20 (16.8%) patients versus 3 (0.3%) controls, yielding a HR of 70.0 (95% CI 20.8 to 235.4), and with a HR for cerebral infarction of 39.9 (95% CI 4.5 to 357.3). Patients with CHB also had a higher risk of infections. Pacemaker treatment was associated with a decreased risk of cerebral infarction but increased risks of cardiomyopathy/heart failure and infection. The risk of systemic connective tissue disorder was also increased in patients with CHB (HR 11.8, 95% CI 4.0 to 11.8), and both patients with CHB and their siblings had an increased risk to develop any of 15 common autoimmune conditions (HR 5.7, 95% CI 2.83 to 11.69 and 3.6, 95% CI 1.7 to 8.0, respectively).

Conclusions: The data indicate an increased risk of several cardiovascular, infectious and autoimmune diseases in patients with CHB, with the latter risk shared by their siblings.
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http://dx.doi.org/10.1136/annrheumdis-2018-214406DOI Listing
May 2019

Perforations and bleeding in a population-based cohort of all registered colonoscopies in Sweden from 2001 to 2013.

United European Gastroenterol J 2019 02 23;7(1):130-137. Epub 2018 Oct 23.

Department of Medicine, Solna, Karolinska Institutet, Stockholm, Sweden.

Background: The rates of perforation and bleeding are important quality measures of colonoscopy performance.

Objective: The objective of this article is to assess the frequency of colonoscopy-related bleeding and perforation in Swedish counties and to relate these findings to patient characteristics.

Method: Data on 593,308 colonoscopies performed on adults from 2001 to 2013 were retrieved from Swedish inpatient and outpatient registers. Covariates were assessed in a multivariate Poisson regression model. The correlation between perforation and bleeding was calculated with Pearson's bivariate correlation formula.

Results: The relative frequency of bleeding and perforation vary across counties (bleeding: 0.02%-0.27%; perforation: 0.02%-0.27%). There were significant positive correlations between the relative frequency of bleeding and perforation at the county level, both including ( = 0.792,  < 0.001) and excluding polypectomies  = 0.814 ( < 0.001). The relative risks of these conditions in the counties ranged from 0.12,  < 0.001, to 1.53,  = 0.05 (bleeding) and from 0.17,  = 0.002, to 2.42,  < 0.001 (perforation).

Conclusions: There are substantial differences in colonoscopy performance in Sweden. These differences do not seem to be explained by patient characteristics.
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http://dx.doi.org/10.1177/2050640618809782DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6374845PMC
February 2019

Fracture Risk in Patients With Inflammatory Bowel Disease: A Nationwide Population-Based Cohort Study From 1964 to 2014.

Am J Gastroenterol 2019 02;114(2):291-304

Patient Area Gastroenterology, Dermatovenerology and Rheumatology, Inflammation and Infection Theme Karolinska University Hospital, Stockholm, Sweden.

Introduction: Most studies on fractures in inflammatory bowel disease (IBD) are based on patients from tertiary centers or patients followed up before the introduction of immunomodulators or biologics. In addition, the role of corticosteroids in fracture risk has rarely been examined.

Methods: We conducted a nationwide population-based cohort study of 83,435 patients with incident IBD (ulcerative colitis [UC]: n = 50,162, Crohn's disease [CD]: n = 26,763, and IBD unclassified: 6,510) and 825,817 reference individuals from 1964 to 2014. Using multivariable Cox regression, we estimated hazard ratios (HRs) for hip fracture and any fracture and the association with cumulative corticosteroid exposure.

Results: During 1,225,415 person-years of follow-up in patients with IBD, there were 2,491 first-time hip fractures (203/100,000 person-years) compared with 20,583 hip fractures during 12,405,642 person-years in reference individuals (159/100,000 person-years). This corresponded to an HR of 1.42 (95% confidence interval [CI] = 1.36-1.48). The risk for hip fracture was higher in CD compared with UC (P < 0.001). Inflammatory bowel disease was also associated with any fracture (IBD: HR = 1.18; 95% CI = 1.15-1.20). Hazard ratios for hip fracture had not changed since the introduction of immunomodulators or biologics. Increasing exposure to corticosteroids was associated with hip fracture in both IBD and non-IBD individuals (P < 0.001), but only in elderly (>60 years) patients with IBD. The association between IBD and hip fracture was nonsignificant among individuals without corticosteroids (HR = 1.11; 95% CI = 0.86-1.44).

Conclusions: Inflammatory bowel disease (CD and UC) is associated with an increased risk of hip fracture and any fracture, but not in individuals without a history of corticosteroid treatment. The association between corticosteroids and hip fracture was restricted to elderly patients with IBD.
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http://dx.doi.org/10.14309/ajg.0000000000000062DOI Listing
February 2019

Changes in inflammatory bowel disease subtype during follow-up and over time in 44,302 patients.

Scand J Gastroenterol 2019 Jan 31;54(1):55-63. Epub 2019 Jan 31.

a Department of Clinical Science and Education , Södersjukhuset, Karolinska Institutet , Stockholm , Sweden.

Aim: To investigate inflammatory bowel disease (IBD) register-based subtype classifications over a patient's disease course and over time.

Methods: We examined International Classification of Diseases coding in patients with ≥2 IBD diagnostic listings in the National Patient Register 2002-2014 (n = 44,302).

Results: 18% of the patients changed diagnosis (17% of adults, 29% of children) during a median follow-up of 3.8 years. Of visits with diagnoses of Crohn's disease (CD) or ulcerative colitis (UC), 97% were followed by the same diagnosis, whereas 67% of visits with diagnosis IBD-unclassified (IBD-U) were followed by another IBD-U diagnosis. Patients with any diagnostic change changed mostly once (47%) or twice (31%), 39% from UC to CD, 33% from CD to UC and 30% to or from IBD-U. Using a classification algorithm based on the first two diagnoses ('incident classification'), suited for prospective cohort studies, the proportion adult patients with CD, UC, and IBD-U 2002-2014 were 29%, 62%, and 10% (43%, 45%, and 12% in children). A classification model incorporating additional information from surgeries and giving weight to the last 5 years of visits ('prevalent classification'), suited for description of a study population at end of follow-up, classified 31% of adult cases as CD, 58% as UC and 11% as IBD-U (44%, 38%, and 18% in children).

Conclusions: IBD subtype changed in 18% during follow-up. The proportion with CD increased and UC decreased from definition at start to end of follow-up. IBD-U was more common in children.
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http://dx.doi.org/10.1080/00365521.2018.1564361DOI Listing
January 2019

Rates and characteristics of postcolonoscopy colorectal cancer in the Swedish IBD population: what are the differences from a non-IBD population?

Gut 2019 09 15;68(9):1588-1596. Epub 2018 Dec 15.

Department of Medicine, Solna (MedS), Karolinska Institutet, Stockholm, Sweden.

Objective: The rate of postcolonoscopy colorectal cancer (PCCRC) is considered a key quality indicator of colonoscopy; little is known about PCCRC in IBD.

Design: A population-based cohort study of colonoscopies in Sweden from 2001 to 2010 was conducted. Individuals with a colorectal cancer (CRC) detected within 36 months after a colonoscopy were identified and stratified on UC, Crohn's disease (CD) or non-IBD. The CRCs were classified as detected CRCs (dCRC) (0-6 months) or as PCCRCs (6-36 months). PCCRC rates were calculated by the number of false negative/(the number of true positive+the number of false negative) colonoscopies. Poisson regression analysis was employed to examine the association between PCCRC and IBD (CD and UC) diagnosis, age, gender, location, time period and comorbidities.

Results: We identified 348 232 colonoscopies in 270 918 individuals. Of these, 27 123 were performed on 14 597 individuals with CD, and 51 572 were performed on 26 513 individuals with UC. There were 13 317 CRCs in the non-IBD group, 133 in the CD group and 281 in the UC group. The PCCRC rate in the CD group was 28.3% and 41.0% in the UC group. The RR for a PCCRC was 3.82 (95% CI 2.94 to 4.96) in CD and 5.89 (95% CI 5.10 to 6.80) in UC, compared with non-IBD. The highest risk was observed among rectal cancer location in CD and in younger individuals with UC.

Conclusion: The high rates of PCCRC in young patients with UC and for rectal cancer location in CD might affect future performance of IBD surveillance.
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http://dx.doi.org/10.1136/gutjnl-2018-316651DOI Listing
September 2019

Male reproductive health statement (XIIIth international symposium on Spermatology, may 9th-12th 2018, Stockholm, Sweden.

Basic Clin Androl 2018 29;28:13. Epub 2018 Oct 29.

22GReD Laboratory INSERM U1103 - CNRS UMR6293, Faculty de Medicine, CRBC, Université Clermont Auvergne (UCA), 63000 Clermont-Ferrand, France.

On the occasion of the held from 9 to 13 May 2018 in Stockholm (Sweden), participants (guest speakers and audience) collectively felt the need to make a public statement on the general issue of male reproductive health. Our intention is to raise awareness of what we believe is a neglected area of research despite alarming situations around the world. The disclosure strategy desired by the co-authors is to bring it to the attention of the greatest number partly by considering co-publication in the various periodicals dealing with Reproductive Biology and Andrology. BaCA's editorial office accepted this mission and found it natural that our periodical, the official journal of the French Andrology Society (SALF), should carry this message.
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http://dx.doi.org/10.1186/s12610-018-0077-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6205799PMC
October 2018
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