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BACKGROUND & AIMS: Earlier studies have provided varying risk estimates for lymphoma in patients with inflam-matory bowel disease (IBD), but often have been limited by detection biases (especially during the first year of follow-up evaluation), misclassification, and small sample size; and rarely reflect modern-day management of IBD.METHODS: We performed a binational register-based cohort study (Sweden and Denmark) from 1969 to 2019. We compared 164,716 patients with IBD with 1,639,027 matched general population reference individuals. Cox regression estimated hazard ratios (HRs) for incident lymphoma by lymphoma subtype, excluding the first year of follow-up evaluation.RESULTS: From 1969 to 2019, 258 patients with Crohn's disease (CD), 479 patients with ulcerative colitis (UC), and 6675 matched reference individuals developed lymphoma. This corresponded to incidence rates of 35 (CD) and 34 (UC) per 100,000 person-years in IBD patients, compared with 28 and 33 per 100,000 person-years in their matched reference individuals. Although both CD (HR, 1.32; 95% CI, 1.16-1.50) and UC (HR, 1.09; 95% CI, 1.00-1.20) were associated with an increase in lymphoma, the 10-year cumulative incidence difference was low even in CD patients (0.08%; 95% CI, 0.02-0.13). HRs have increased in the past 2 decades, corresponding to increasing use of immunomodulators and biologics during the same time period. HRs were increased for aggressive B-cell non-Hodgkin lymphoma in CD and UC patients, and for T-cell non-Hodgkin lymphoma in CD patients. Although the highest HRs were observed in patients exposed to combination therapy (immunomodulators and biologics) or second-line biologics, we also found increased HRs in patients naive to such drugs.CONCLUSIONS: During the past 20 years, the risk of lymphomas have increased in CD, but not in UC, and were driven mainly by T-cell lymphomas and aggressive B-cell lymphomas., Funding Agencies|Swedish Medical Society grant [SLS-789611]; Strategiskt Forskningsomrade Young Scholar Award at Karolinska Institutet, Avtal om Laekarutbildning och Forskning (ALF) [20170720, 20190638]; Swedish Research Council [2020-02002]; Swedish Cancer Society; Stockholm County Council (ALF); Swedish Foundation for Strategic Research; Independent Research Fund Denmark; Forskningsradet for halsa, arbetsliv och valfard Foundation; Swedish Cancer Foundation

BACKGROUND & AIMS: Earlier studies have provided varying risk estimates for lymphoma in patients with inflam-matory bowel disease (IBD), but often have been limited by detection biases (especially during the first year of follow-up evaluation), misclassification, and small sample size; and rarely reflect modern-day management of IBD.METHODS: We performed a binational register-based cohort study (Sweden and Denmark) from 1969 to 2019. We compared 164,716 patients with IBD with 1,639,027 matched general population reference individuals. Cox regression estimated hazard ratios (HRs) for incident lymphoma by lymphoma subtype, excluding the first year of follow-up evaluation.RESULTS: From 1969 to 2019, 258 patients with Crohn's disease (CD), 479 patients with ulcerative colitis (UC), and 6675 matched reference individuals developed lymphoma. This corresponded to incidence rates of 35 (CD) and 34 (UC) per 100,000 person-years in IBD patients, compared with 28 and 33 per 100,000 person-years in their matched reference individuals. Although both CD (HR, 1.32; 95% CI, 1.16-1.50) and UC (HR, 1.09; 95% CI, 1.00-1.20) were associated with an increase in lymphoma, the 10-year cumulative incidence difference was low even in CD patients (0.08%; 95% CI, 0.02-0.13). HRs have increased in the past 2 decades, corresponding to increasing use of immunomodulators and biologics during the same time period. HRs were increased for aggressive B-cell non-Hodgkin lymphoma in CD and UC patients, and for T-cell non-Hodgkin lymphoma in CD patients. Although the highest HRs were observed in patients exposed to combination therapy (immunomodulators and biologics) or second-line biologics, we also found increased HRs in patients naive to such drugs.CONCLUSIONS: During the past 20 years, the risk of lymphomas have increased in CD, but not in UC, and were driven mainly by T-cell lymphomas and aggressive B-cell lymphomas., Funding Agencies|Swedish Medical Society grant [SLS-789611]; Strategiskt Forskningsomrade Young Scholar Award at Karolinska Institutet, Avtal om Laekarutbildning och Forskning (ALF) [20170720, 20190638]; Swedish Research Council [2020-02002]; Swedish Cancer Society; Stockholm County Council (ALF); Swedish Foundation for Strategic Research; Independent Research Fund Denmark; Forskningsradet for halsa, arbetsliv och valfard Foundation; Swedish Cancer Foundation

BACKGROUND & AIMS: Earlier studies have provided varying risk estimates for lymphoma in patients with inflam-matory bowel disease (IBD), but often have been limited by detection biases (especially during the first year of follow-up evaluation), misclassification, and small sample size; and rarely reflect modern-day management of IBD.METHODS: We performed a binational register-based cohort study (Sweden and Denmark) from 1969 to 2019. We compared 164,716 patients with IBD with 1,639,027 matched general population reference individuals. Cox regression estimated hazard ratios (HRs) for incident lymphoma by lymphoma subtype, excluding the first year of follow-up evaluation.RESULTS: From 1969 to 2019, 258 patients with Crohn's disease (CD), 479 patients with ulcerative colitis (UC), and 6675 matched reference individuals developed lymphoma. This corresponded to incidence rates of 35 (CD) and 34 (UC) per 100,000 person-years in IBD patients, compared with 28 and 33 per 100,000 person-years in their matched reference individuals. Although both CD (HR, 1.32; 95% CI, 1.16-1.50) and UC (HR, 1.09; 95% CI, 1.00-1.20) were associated with an increase in lymphoma, the 10-year cumulative incidence difference was low even in CD patients (0.08%; 95% CI, 0.02-0.13). HRs have increased in the past 2 decades, corresponding to increasing use of immunomodulators and biologics during the same time period. HRs were increased for aggressive B-cell non-Hodgkin lymphoma in CD and UC patients, and for T-cell non-Hodgkin lymphoma in CD patients. Although the highest HRs were observed in patients exposed to combination therapy (immunomodulators and biologics) or second-line biologics, we also found increased HRs in patients naive to such drugs.CONCLUSIONS: During the past 20 years, the risk of lymphomas have increased in CD, but not in UC, and were driven mainly by T-cell lymphomas and aggressive B-cell lymphomas., Funding Agencies|Swedish Medical Society grant [SLS-789611]; Strategiskt Forskningsomrade Young Scholar Award at Karolinska Institutet, Avtal om Laekarutbildning och Forskning (ALF) [20170720, 20190638]; Swedish Research Council [2020-02002]; Swedish Cancer Society; Stockholm County Council (ALF); Swedish Foundation for Strategic Research; Independent Research Fund Denmark; Forskningsradet for halsa, arbetsliv och valfard Foundation; Swedish Cancer Foundation

Jesper Nors,1,2,* Trine Block Mattesen,1,* Deirdre Cronin-Fenton,3 Aurélie Mailhac,3 Jesper Bertram Bramsen,1,2 Kåre Andersson Gotschalck,2,4 Rune Erichsen,2,3,5 Claus Lindbjerg Andersen1,2 1Department of Molecular Medicine, Aarhus University Hospital, Aarhus, Denmark; 2Department of Clinical Medicine, Aarhus University Hospital, Aarhus, Denmark; 3Department of Clinical Epidemiology, Aarhus University Hospital, Aarhus, Denmark; 4Department of Surgery, Horsens Regional Hospital, Horsens, Denmark; 5Department of Surgery, Randers Regional Hospital, Horsens, Denmark*These authors contributed equally to this workCorrespondence: Claus Lindbjerg Andersen, Department of Molecular Medicine, Aarhus University Hospital, Palle Juul-Jensens Boulevard 99, Aarhus N, DK-8200, Denmark, Tel +45 78455319, Email cla@clin.au.dkPurpose: Colorectal cancer (CRC) recurrence is not routinely recorded in Danish health data registries. Here, we aimed to revalidate a registry-based algorithm to identify recurrences in a contemporary cohort and to investigate the accuracy of estimating the time to recurrence (TTR).Patients and Methods: We ascertained data on 1129 patients operated for UICC TNM stage I–III CRC during 2012– 2017 registered in the CRC biobank at the Department of Molecular Medicine, Aarhus University Hospital, Denmark. Individual-level data were linked with data from the Danish Colorectal Cancer Group database, Danish Cancer Registry, Danish National Registry of Patients, and Danish Pathology Registry. The algorithm identified recurrence based on diagnosis codes of local recurrence or metastases, the receipt of chemotherapy, or a pathological tissue assessment code of recurrence more than 180 days after CRC surgery. A subgroup was selected for validation of the algorithm using medical record reviews as a reference standard.Results: We found a 3-year cumulative recurrence rate of 20% (95% CI: 17– 22%). Manual medical record review identified 80 recurr

Background The aim of this study was to examine the association between appendectomy and advanced colorectal neoplasia (aCRN) in patients with inflammatory bowel disease (IBD). Methods Inflammatory bowel disease patients diagnosed in Denmark in the period 1977 to 2017 were identified from the Danish National Patient Registry. Inflammatory bowel disease patients who underwent appendectomy were matched with up to 10 IBD patients without appendectomy and followed until aCRN, death, or emigration. Absolute risks of aCRN were calculated, treating death and bowel resections as competing risks. Stratified Cox regression was used to calculate adjusted hazard ratios (aHRs) of aCRN, comparing IBD patients with appendectomy to IBD patients without appendectomy. Results We identified 3789 IBD patients with appendectomy and 37 676 IBD patients without appendectomy. A total of 573 patients (1.4%) developed aCRN, with an absolute risk of aCRN at 20 years of 4.9% (95% confidence interval [CI], 2.9%-7.7%) for ulcerative colitis (UC) patients with appendectomy after UC diagnosis compared with 2.8% (95% CI, 2.3%-3.3%) for UC patients without appendectomy. Appendectomy after UC was associated with an increased rate of aCRN 5 to 10 years (aHR, 2.5; 95% CI, 1.1-5.5) and 10 to 20 years after appendectomy (aHR, 2.3; 95% CI, 1.0-5.5). Appendectomy prior to UC diagnosis was not associated with an increased rate of aCRN, and Crohns disease was not associated with the rate of aCRN, regardless of timing or histological diagnosis of the appendix specimen. Conclusions Although appendectomy may have a positive effect on the clinical course of UC, our study suggests that this may come at the expense of a higher risk of aCRN., Funding Agencies|Novo Nordisk Foundation [NNF19OC0058609]

Background and objective: We aimed to validate the diagnostic accuracy of appendicitis, its severity, its description, and the surgical approach, including open or laparoscopic appendectomy and diagnostic laparoscopy, in the Danish National Patient Registry (DNPR) against information from the electronic medical records. Methods: A random sample of 1046 patients of all ages and sexes recorded in the DNPR from the Capital Region of Denmark during 2010–2015 was investigated. Patients’ admission had to include a discharge code for appendicitis (K35−K379) according to the International Classification of Disease version 10 (ICD-10) alone or in combination with a surgical code for appendectomy or the surgical code for a diagnostic laparoscopy. We calculated the positive predictive values (PPVs) with 95% confidence intervals. Results: Data from a total of 1018 patients were available for data analysis. The ICD-10 codes for appendicitis resulted in a good PPV of >95% when combined with a surgical code. ICD-10 codes combined with the surgical codes could discriminate between uncomplicated and complicated appendicitis with some caution as the PPVs ranged from 68% to 93%. Only the surgical code for laparoscopic appendectomy yielded a good PPV (99%) for the actual surgical approach. The surgical code for a diagnostic laparoscopy alone did not cover a normal diagnostic laparoscopy. Conclusions: The diagnostic accuracy of appendicitis and appendectomy in routinely collected administrative health data is good for ICD-10 codes for appendicitis in combination with a surgical code and especially for laparoscopic appendectomy. Uncomplicated and complicated appendicitis can be distinguished with some caution.

BACKGROUND & AIMS: Earlier studies have provided varying risk estimates for lymphoma in patients with inflammatory bowel disease (IBD) but have often been limited by detection biases, (especially during the first year of follow-up), misclassification, and small sample size; and rarely reflect modern-day management of IBD. METHODS: Binational register-based cohort study (Sweden and Denmark) during 1969-2019. We compared 164,716 patients with IBD to 1,639,027 matched general population reference individuals. Cox regression estimated hazard ratios (HRs) for incident lymphoma by lymphoma subtype, excluding the first year of follow-up. RESULTS: During 1969-2019, 258 patients with Crohn's Disease (CD), 479 patients with ulcerative colitis (UC), and 6675 matched reference individuals developed lymphoma. This corresponded to incidence rates of 35(CD) and 34(UC)/100,000 person-years [PY] in IBD patients, compared to 28 and 33/100,000 PY in their matched reference individuals. While both CD (HR=1.32; 95%CI=1.16-1.50) and UC (HR=1.09; 95%CI=1.00-1.20) were associated with an increase in lymphoma, the 10-year cumulative incidence difference was low even in CD patients (0.08%; 95%CI=0.02 to 0.13])). HRs increased the past two decades, corresponding to increasing use of immunomodulators and biologics during the same time-period. HRs were increased for aggressive B-cell NHL in CD and UC patients, and for T-cell NHL in CD patients. Although the highest HRs were observed in patients exposed to combination therapy (immunomodulators and biologics) or second line biologics, we also found increased HRs in patients naïve to such drugs. CONCLUSIONS: During the past 20 years, HRs for lymphomas have increased in CD, but not in UC, and were driven mainly by T-cell lymphomas and aggressive B-cell lymphomas., Supported by Swedish Medical Society grant Dnr SLS-789611, the Strategiskt Forskningsomrade Young Scholar Award at Karolinska Institutet, Avtal om Läkarutbildning och Forskning (ALF) grants Dnr 20170720 and 20190638, and the Swedish Research Council grant Dnr 2020-02002 (O.O.) ; by the Swedish Cancer Society, the Stockholm County Council (ALF) , the Swedish Research Council, and the Swedish Foundation for Strategic Research during the conduct of the study (J.A.) ; by a grant from the Independent Research Fund Denmark (H.T.S.) ; and by the Forskningsrådet for hälsa, arbetsliv och välfärd Foundation and the Swedish Cancer Foundation (J.F.L.) .

Background & Aims: Earlier studies have provided varying risk estimates for lymphoma in patients with inflammatory bowel disease (IBD), but often have been limited by detection biases (especially during the first year of follow-up evaluation), misclassification, and small sample size; and rarely reflect modern-day management of IBD. Methods: We performed a binational register-based cohort study (Sweden and Denmark) from 1969 to 2019. We compared 164,716 patients with IBD with 1,639,027 matched general population reference individuals. Cox regression estimated hazard ratios (HRs) for incident lymphoma by lymphoma subtype, excluding the first year of follow-up evaluation. Results: From 1969 to 2019, 258 patients with Crohn's disease (CD), 479 patients with ulcerative colitis (UC), and 6675 matched reference individuals developed lymphoma. This corresponded to incidence rates of 35 (CD) and 34 (UC) per 100,000 person-years in IBD patients, compared with 28 and 33 per 100,000 person-years in their matched reference individuals. Although both CD (HR, 1.32; 95% CI, 1.16–1.50) and UC (HR, 1.09; 95% CI, 1.00–1.20) were associated with an increase in lymphoma, the 10-year cumulative incidence difference was low even in CD patients (0.08%; 95% CI, 0.02–0.13). HRs have increased in the past 2 decades, corresponding to increasing use of immunomodulators and biologics during the same time period. HRs were increased for aggressive B-cell non-Hodgkin lymphoma in CD and UC patients, and for T-cell non-Hodgkin lymphoma in CD patients. Although the highest HRs were observed in patients exposed to combination therapy (immunomodulators and biologics) or second-line biologics, we also found increased HRs in patients naïve to such drugs. Conclusions: During the past 20 years, the risk of lymphomas have increased in CD, but not in UC, and were driven mainly by T-cell lymphomas and aggressive B-cell lymphomas.

BACKGROUND & AIMS: Earlier studies have provided varying risk estimates for lymphoma in patients with inflam-matory bowel disease (IBD), but often have been limited by detection biases (especially during the first year of follow-up evaluation), misclassification, and small sample size; and rarely reflect modern-day management of IBD.METHODS: We performed a binational register-based cohort study (Sweden and Denmark) from 1969 to 2019. We compared 164,716 patients with IBD with 1,639,027 matched general population reference individuals. Cox regression estimated hazard ratios (HRs) for incident lymphoma by lymphoma subtype, excluding the first year of follow-up evaluation.RESULTS: From 1969 to 2019, 258 patients with Crohn's disease (CD), 479 patients with ulcerative colitis (UC), and 6675 matched reference individuals developed lymphoma. This corresponded to incidence rates of 35 (CD) and 34 (UC) per 100,000 person-years in IBD patients, compared with 28 and 33 per 100,000 person-years in their matched reference individuals. Although both CD (HR, 1.32; 95% CI, 1.16-1.50) and UC (HR, 1.09; 95% CI, 1.00-1.20) were associated with an increase in lymphoma, the 10-year cumulative incidence difference was low even in CD patients (0.08%; 95% CI, 0.02-0.13). HRs have increased in the past 2 decades, corresponding to increasing use of immunomodulators and biologics during the same time period. HRs were increased for aggressive B-cell non-Hodgkin lymphoma in CD and UC patients, and for T-cell non-Hodgkin lymphoma in CD patients. Although the highest HRs were observed in patients exposed to combination therapy (immunomodulators and biologics) or second-line biologics, we also found increased HRs in patients naive to such drugs.CONCLUSIONS: During the past 20 years, the risk of lymphomas have increased in CD, but not in UC, and were driven mainly by T-cell lymphomas and aggressive B-cell lymphomas., Funding Agencies|Swedish Medical Society grant [SLS-789611]; Strategiskt Forskningsomrade Young Scholar Award at Karolinska Institutet, Avtal om Laekarutbildning och Forskning (ALF) [20170720, 20190638]; Swedish Research Council [2020-02002]; Swedish Cancer Society; Stockholm County Council (ALF); Swedish Foundation for Strategic Research; Independent Research Fund Denmark; Forskningsradet for halsa, arbetsliv och valfard Foundation; Swedish Cancer Foundation

BACKGROUND & AIMS: Earlier studies have provided varying risk estimates for lymphoma in patients with inflam-matory bowel disease (IBD), but often have been limited by detection biases (especially during the first year of follow-up evaluation), misclassification, and small sample size; and rarely reflect modern-day management of IBD.METHODS: We performed a binational register-based cohort study (Sweden and Denmark) from 1969 to 2019. We compared 164,716 patients with IBD with 1,639,027 matched general population reference individuals. Cox regression estimated hazard ratios (HRs) for incident lymphoma by lymphoma subtype, excluding the first year of follow-up evaluation.RESULTS: From 1969 to 2019, 258 patients with Crohn's disease (CD), 479 patients with ulcerative colitis (UC), and 6675 matched reference individuals developed lymphoma. This corresponded to incidence rates of 35 (CD) and 34 (UC) per 100,000 person-years in IBD patients, compared with 28 and 33 per 100,000 person-years in their matched reference individuals. Although both CD (HR, 1.32; 95% CI, 1.16-1.50) and UC (HR, 1.09; 95% CI, 1.00-1.20) were associated with an increase in lymphoma, the 10-year cumulative incidence difference was low even in CD patients (0.08%; 95% CI, 0.02-0.13). HRs have increased in the past 2 decades, corresponding to increasing use of immunomodulators and biologics during the same time period. HRs were increased for aggressive B-cell non-Hodgkin lymphoma in CD and UC patients, and for T-cell non-Hodgkin lymphoma in CD patients. Although the highest HRs were observed in patients exposed to combination therapy (immunomodulators and biologics) or second-line biologics, we also found increased HRs in patients naive to such drugs.CONCLUSIONS: During the past 20 years, the risk of lymphomas have increased in CD, but not in UC, and were driven mainly by T-cell lymphomas and aggressive B-cell lymphomas., Funding Agencies|Swedish Medical Society grant [SLS-789611]; Strategiskt Forskningsomrade Young Scholar Award at Karolinska Institutet, Avtal om Laekarutbildning och Forskning (ALF) [20170720, 20190638]; Swedish Research Council [2020-02002]; Swedish Cancer Society; Stockholm County Council (ALF); Swedish Foundation for Strategic Research; Independent Research Fund Denmark; Forskningsradet for halsa, arbetsliv och valfard Foundation; Swedish Cancer Foundation

Background and objective: We aimed to validate the diagnostic accuracy of appendicitis, its severity, its description, and the surgical approach, including open or laparoscopic appendectomy and diagnostic laparoscopy, in the Danish National Patient Registry (DNPR) against information from the electronic medical records. Methods: A random sample of 1046 patients of all ages and sexes recorded in the DNPR from the Capital Region of Denmark during 2010–2015 was investigated. Patients’ admission had to include a discharge code for appendicitis (K35−K379) according to the International Classification of Disease version 10 (ICD-10) alone or in combination with a surgical code for appendectomy or the surgical code for a diagnostic laparoscopy. We calculated the positive predictive values (PPVs) with 95% confidence intervals. Results: Data from a total of 1018 patients were available for data analysis. The ICD-10 codes for appendicitis resulted in a good PPV of >95% when combined with a surgical code. ICD-10 codes combined with the surgical codes could discriminate between uncomplicated and complicated appendicitis with some caution as the PPVs ranged from 68% to 93%. Only the surgical code for laparoscopic appendectomy yielded a good PPV (99%) for the actual surgical approach. The surgical code for a diagnostic laparoscopy alone did not cover a normal diagnostic laparoscopy. Conclusions: The diagnostic accuracy of appendicitis and appendectomy in routinely collected administrative health data is good for ICD-10 codes for appendicitis in combination with a surgical code and especially for laparoscopic appendectomy. Uncomplicated and complicated appendicitis can be distinguished with some caution.

Aim Patients with inflammatory bowel disease (IBD) may undergo several abdominal surgeries with a risk of incisional hernia repair (IHR). The objectives of this study were to establish the risk of IHR and to analyse predictors of IHR after a first-time abdominal surgery for IBD. Method This Danish nationwide register-based cohort study (1996–2018) followed IBD patients from index operation until the date of IHR. The absolute risk was calculated as the cumulative incidence proportion treating death as a competing risk. Cox proportional hazard regression was used to compare the risk of IHR among different subtypes of IBD and to explore predictors of IHR. IBD subtypes were classified as ulcerative colitis (UC), Crohn's disease (CD) or unclassified IBD (IBD-U). Results In total, 10 130 patients with IBD (UC 3911 [39%]; CD 4210 [41%]; IBD-U 2009 [20%]) underwent either an open or a laparoscopic index operation. The 10-year cumulative incidence of IHR varied between 5.0% and 6.3%, with a significantly higher risk in patients with UC and IBD-U. Patients with UC (75.9%) and IBD-U (91.9%) had more (two or more) abdominal surgeries in the follow-up period compared with CD (51.9%). The risk of IHR increased dramatically with the number of surgeries, although not as markedly if a laparoscopic approach was used. Male sex, age, comorbidity, fascial dehiscence, wound infection and presence of stoma were predictors of IHR for patients with IBD. Conclusion The long-term risk of IHR was roughly 5%–6%, with a higher risk in patients with UC and IBD-U. Open surgical approach and number of previous surgeries were, among other things, important predictors of IHR., Aim: Patients with inflammatory bowel disease (IBD) may undergo several abdominal surgeries with a risk of incisional hernia repair (IHR). The objectives of this study were to establish the risk of IHR and to analyse predictors of IHR after a first-time abdominal surgery for IBD. Method: This Danish nationwide register-based cohort study (1996–2018) followed IBD patients from index operation until the date of IHR. The absolute risk was calculated as the cumulative incidence proportion treating death as a competing risk. Cox proportional hazard regression was used to compare the risk of IHR among different subtypes of IBD and to explore predictors of IHR. IBD subtypes were classified as ulcerative colitis (UC), Crohn's disease (CD) or unclassified IBD (IBD-U). Results: In total, 10 130 patients with IBD (UC 3911 [39%]; CD 4210 [41%]; IBD-U 2009 [20%]) underwent either an open or a laparoscopic index operation. The 10-year cumulative incidence of IHR varied between 5.0% and 6.3%, with a significantly higher risk in patients with UC and IBD-U. Patients with UC (75.9%) and IBD-U (91.9%) had more (two or more) abdominal surgeries in the follow-up period compared with CD (51.9%). The risk of IHR increased dramatically with the number of surgeries, although not as markedly if a laparoscopic approach was used. Male sex, age, comorbidity, fascial dehiscence, wound infection and presence of stoma were predictors of IHR for patients with IBD. Conclusion: The long-term risk of IHR was roughly 5%–6%, with a higher risk in patients with UC and IBD-U. Open surgical approach and number of previous surgeries were, among other things, important predictors of IHR.

Aim Patients with inflammatory bowel disease (IBD) may undergo several abdominal surgeries with a risk of incisional hernia repair (IHR). The objectives of this study were to establish the risk of IHR and to analyse predictors of IHR after a first-time abdominal surgery for IBD. Method This Danish nationwide register-based cohort study (1996–2018) followed IBD patients from index operation until the date of IHR. The absolute risk was calculated as the cumulative incidence proportion treating death as a competing risk. Cox proportional hazard regression was used to compare the risk of IHR among different subtypes of IBD and to explore predictors of IHR. IBD subtypes were classified as ulcerative colitis (UC), Crohn's disease (CD) or unclassified IBD (IBD-U). Results In total, 10 130 patients with IBD (UC 3911 [39%]; CD 4210 [41%]; IBD-U 2009 [20%]) underwent either an open or a laparoscopic index operation. The 10-year cumulative incidence of IHR varied between 5.0% and 6.3%, with a significantly higher risk in patients with UC and IBD-U. Patients with UC (75.9%) and IBD-U (91.9%) had more (two or more) abdominal surgeries in the follow-up period compared with CD (51.9%). The risk of IHR increased dramatically with the number of surgeries, although not as markedly if a laparoscopic approach was used. Male sex, age, comorbidity, fascial dehiscence, wound infection and presence of stoma were predictors of IHR for patients with IBD. Conclusion The long-term risk of IHR was roughly 5%–6%, with a higher risk in patients with UC and IBD-U. Open surgical approach and number of previous surgeries were, among other things, important predictors of IHR., Aim: Patients with inflammatory bowel disease (IBD) may undergo several abdominal surgeries with a risk of incisional hernia repair (IHR). The objectives of this study were to establish the risk of IHR and to analyse predictors of IHR after a first-time abdominal surgery for IBD. Method: This Danish nationwide register-based cohort study (1996–2018) followed IBD patients from index operation until the date of IHR. The absolute risk was calculated as the cumulative incidence proportion treating death as a competing risk. Cox proportional hazard regression was used to compare the risk of IHR among different subtypes of IBD and to explore predictors of IHR. IBD subtypes were classified as ulcerative colitis (UC), Crohn's disease (CD) or unclassified IBD (IBD-U). Results: In total, 10 130 patients with IBD (UC 3911 [39%]; CD 4210 [41%]; IBD-U 2009 [20%]) underwent either an open or a laparoscopic index operation. The 10-year cumulative incidence of IHR varied between 5.0% and 6.3%, with a significantly higher risk in patients with UC and IBD-U. Patients with UC (75.9%) and IBD-U (91.9%) had more (two or more) abdominal surgeries in the follow-up period compared with CD (51.9%). The risk of IHR increased dramatically with the number of surgeries, although not as markedly if a laparoscopic approach was used. Male sex, age, comorbidity, fascial dehiscence, wound infection and presence of stoma were predictors of IHR for patients with IBD. Conclusion: The long-term risk of IHR was roughly 5%–6%, with a higher risk in patients with UC and IBD-U. Open surgical approach and number of previous surgeries were, among other things, important predictors of IHR.

BACKGROUND: Previous research indicates that the increased relative risk of colorectal cancer (CRC) in inflammatory bowel disease (IBD) is limited to young-onset IBD. AIM: To estimate risks of incident CRC and death from CRC in elderly-onset IBD METHODS: Patients diagnosed with IBD at age ≥ 60 years between 1969 and 2017 were identified using Danish and Swedish National Patient Registers and histopathology data. We linked data to Cancer and Causes of Death Registers and used Cox regression to estimate hazard ratios (HRs) for CRC diagnosis and death compared to matched (by sex, age, and region) IBD-free individuals. RESULTS: Among 7869 patients with Crohn's disease followed for 54,220 person-years, and 21,224 patients with ulcerative colitis (UC) followed for 142,635 person-years, 2.10% and 1.90% were diagnosed with CRC, compared to 2.26% and 2.34% of reference individuals (median follow-up 6 and 7 years). The incidence of CRC was elevated during the first year after IBD diagnosis: 4.36 (95% CI = 3.33-5.71) in Crohn's disease and 2.48 (95% CI = 2.03-3.02) in UC, but decreased after the first year of follow-up: 0.69 (95% CI = 0.56-0.86) and 0.78 (95% CI = 0.69-0.88). Once diagnosed with CRC, the risk of CRC death was similar for IBD patients and the general population. CONCLUSION: The excess risk of CRC in elderly-onset IBD was probably due to bias and not observed beyond the first year. From 2010, the HR for CRC diagnosis more than 1 year after initial IBD diagnosis was lower than in the largely unscreened reference population, supporting the benefit of endoscopic screening and surveillance in patients with IBD., Funding agencies:Bengt Ihres FoundationDanish Cancer Association Independent Research Fund Denmark

Through linkage of data from Danish and Swedish national registers we identified 6937 patients with childhood (<18 years)-onset Crohn disease (CD), 8514 patients with childhood-onset ulcerative colitis (UC) and up to 10 times as many matched (sex, age, residence) reference individuals 1969-2017. During follow-up to a median age of 27 (interquartile range = 21-39) years, 25 (0.36%) CD patients were diagnosed with colorectal cancer (CRC) versus 43 (0.06%) reference individuals, and 113 (1.33%) UC patients versus 45 (0.05%) reference individuals. The hazard ratio (HR) for CRC was 6.46 (95% CI = 3.95-10.6) in CD and 32.5 (95% CI = 23.0-45.9) in UC and increased with decreasing age at diagnosis. The HR for CRC was increased for all phenotypes, but with higher estimates for colonic CD [17.9 (95% CI = 7.43-43.3)] and UC with extensive/pancolitis [36.3 (95% CI = 22.8-57.8)]. The relative risk of CRC was increased for all phenotypes of childhood-onset inflammatory bowel disease. Age at onset may be considered an additional risk factor when implementing surveillance programs., Funding agencies:Bengt Ihre Research Foundation Bengt Ihre Research FellowshipYoung Scholar Award from the Strategic Research Area Epidemiology Program at Karolinska InstitutetIndependent Research Fund Denmark Danish Cancer AssociationRegional Agreement on Medical Training and Clinical Research between Stockholm County Council

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., Funding Agencies:NYU School of Medicine Swedish Medical Society (Fund for Research in Gastroenterology and Ihre Foundation) Mag-tarmfonden Strategic Research Area Epidemiology Program at Karolinska Institutet Danish Cancer Association Nordic Research Council Independent Research Fund Denmark

Louise Thomsen,* Frederikke Schønfeldt Troelsen,* David Nagy, Nils Skajaa, Dóra Körmendiné Farkas, Rune Erichsen Department of Clinical Epidemiology, Aarhus University Hospital, Aarhus N, 8200, Denmark*These authors contributed equally to this workCorrespondence: Louise ThomsenDepartment of Clinical Epidemiology, Aarhus University Hospital, Olof Palmes Allé 43-45, Aarhus N, 8200, DenmarkTel +45 20477642Email louisethomsen3@gmail.comPurpose: Venous thromboembolism may be a harbinger of cancer. Patients with diverticular disease are suggested to have an increased risk of developing venous thromboembolism compared with the general population, but it remains unclear whether venous thromboembolism is also a marker of occult cancer in these patients. We investigated the risk of cancer after venous thromboembolism among patients with diverticular disease.Patients and Methods: We used Danish health registries to conduct a nationwide, population-based cohort study during 1996– 2017. We identified all venous thromboembolism patients with a diagnosis of diverticular disease and calculated absolute risks of cancer and standardized incidence ratios (SIRs) by comparing observed and expected cancer incidence based on national cancer incidence in the Danish population.Results: We followed 3406 patients with venous thromboembolism and diverticular disease for a median of 3.0 years (interquartile range: 1.0– 6.0). During the first year of follow-up, we observed 212 cancer cases. The corresponding one-year risk of cancer was 6.2% (95% confidence interval [CI]: 5.5– 7.1) with a SIR of 2.9 (95% CI: 2.5– 3.3). The SIRs were particularly elevated for cancers of the stomach, pancreas, ovary, and kidney. During the second and subsequent years of follow-up, 337 cancers were diagnosed with a SIR of 1.1 (95% CI: 1.0– 1.3).Conclusion: Venous thromboembolism is a harbinger of occult ca

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., Funding Agencies:NYU School of Medicine Swedish Medical Society (Fund for Research in Gastroenterology and Ihre Foundation) Mag-tarmfonden Strategic Research Area Epidemiology Program at Karolinska Institutet Danish Cancer Association Nordic Research Council Independent Research Fund 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 (n = 28), ICC (n = 28), and ECC (n = 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., Funding agencies:Independent Research Fund Denmark 8020-00153B Young Scholar Award from the Strategic Research Area Epidemiology Program at Karolinska Institutet

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, Funding Agencies:Swedish Medical Society (Fund for Research in Gastroenterology) Swedish Medical Society (Ihre Foundation) Mag-tarmfonden Young Scholar Award from the Strategic Research Area Epidemiology programme at Karolinska Institutet Independent Research Fund Denmark

Lindsay J Collin,1,2 Anders H Riis,2 Richard F MacLehose,3 Thomas P Ahern,4 Rune Erichsen,2,5 Ole Thorlacius-Ussing,6 Timothy L Lash1 1Department of Epidemiology, Emory University, Atlanta, GA, USA; 2Department of Clinical Epidemiology, Aarhus University Hospital, Aarhus, Denmark; 3Division of Epidemiology and Community Health, University of Minnesota, Minneapolis, MN, USA; 4Department of Surgery, The Robert Larner, M.D. College of Medicine at the University of Vermont, Burlington, VT, USA; 5Department of Surgery, Randers Regional Hospital, Randers, Denmark; 6Department of Gastrointestinal Surgery, Aalborg University Hospital, Aalborg, DenmarkCorrespondence: Lindsay J CollinDepartment of Epidemiology, Emory University, 1518 Clifton RoadNE, Atlanta, GA 30322, USATel +1 530-386-3341Email lindsay.jane.collin@emory.eduBackground: Among men and women diagnosed with colorectal cancer (CRC), 20– 50% will develop a cancer recurrence. Cancer recurrences are not routinely captured by most population-based registries; however, linkage across Danish registries allows for the development of predictive models to detect recurrence. Successful application of such models in population-based settings requires validation against a gold standard to ensure the accuracy of recurrence identification.Objective: We apply a recently developed validation study design for prospectively collected validation data to validate predicted CRC recurrences against gold standard diagnoses from medical records in an actively followed cohort of CRC patients in Denmark.Methods: We use a Bayesian monitoring framework, traditionally used in clinical trials, to iteratively update classification parameters (positive and negative predictive values, and sensitivity and specificity) in an adaptive validation substudy design. This design allows determination of the sample size necessary to estimate the corresponding parameters and to identify when validation efforts can cease based on predefined criteri

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, Funding Agencies:Swedish Medical Society (Fund for Research in Gastroenterology) Swedish Medical Society (Ihre Foundation) Mag-tarmfonden Young Scholar Award from the Strategic Research Area Epidemiology programme at Karolinska Institutet Independent Research Fund Denmark

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., Funding Agencies:Bengt Ihre Research Foundation, Bengt Ihre Research FellowshipStrategic Research Area Epidemiology program at Karolinska InstitutetIndependent Research Fund Denmark Danish Cancer Association

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 i, Funding Agency:Independent Research Fund Denmark

Tue Højslev Avlund,1 Rune Erichsen,1,2 Lene Hjerrild Iversen1,2 1Department of Surgery, Aarhus University Hospital, Aarhus, Denmark; 2Department of Clinical Epidemiology, Aarhus University Hospital, Aarhus, Denmark Background: Randomized controlled trials have not provided clear evidence for the use of self-expanding metal stents (SEMS) for colonic cancer obstruction. Existing observational research mainly originates from highly specialized single-center settings with limited generalizability. The conduct of population-based nationwide studies is possible by using Danish medical databases. However, the quality of the coding of SEMS procedures in these databases is unclear. Methods: From March 1, 2010 through December 31, 2013, we compared the registration of SEMS procedures among obstructive colorectal cancer patients in the Danish National Patient Register (DNPR) and the Danish Colorectal Cancer Group (DCCG) database to the registration in a prospective SEMS database (the reference standard). Results: Ninety-three patients were included in the reference standard for the evaluation of DNPR data. In the DNPR, only two patients were incorrectly registered (positive predictive value [PPV]=98%, 95% CI: 92%–100%) whereas six patients were not captured by the DNPR (sensitivity =94%, 95% CI: 87%–98%). For the evaluation of the DCCG database, the reference standard included 54 patients. Only two patients in the DCCG database were incorrectly recorded (PPV =95%, 95% CI: 82%–99%), whereas 19 patients were not captured by the DCCG database (sensitivity =65%, 95% CI: 51%–77%). Conclusion: We found high PPV and sensitivity of SEMS coding in the DNPR, supporting the use of these data in future research. The PPV of SEMS data in the DCCG database was high, but the sensitivity was low, suggesting that data on SEMS treatment from this database should be used with caution. Keywords: validation study

Jonathan Montomoli, Rune Erichsen, Henrik Gammelager, Alma B Pedersen Department of Clinical Epidemiology, Aarhus University Hospital, Aarhus N, Denmark Purpose: The aim of this study was to examine the prognostic impact of liver disease on mortality following hip fracture (HF). Patients and methods: This nationwide cohort study, based on prospectively collected data retrieved from Danish registries, included all patients diagnosed with incident HF in Denmark during 1996–2013. Patients were classified based on the coexisting liver disease at the time of HF, ie, no liver disease, noncirrhotic liver disease, and liver cirrhosis. We computed 30-day and 31–365-day mortality risks. To compare patients with and without liver disease, we computed mortality adjusted hazard ratios (HRs) and corresponding 95% confidence intervals (CIs) using Cox regression controlled for potential confounders. Results: Among 152,180 HF patients, 2,552 (1.7%) patients had noncirrhotic liver disease and 1,866 (1.2%) patients had liver cirrhosis. Thirty-day mortality was 9.4% among patients with noncirrhotic liver disease, 12.6% among patients with liver cirrhosis patients, and 9.7% among patients without liver disease. Compared to patients without liver disease, crude and adjusted HRs within 30 days following HF were, respectively, 0.96 (95% CI: 0.85–1.10) and 1.24 (95% CI: 1.09–1.41) for patients with noncirrhotic liver disease and 1.30 (95% CI: 1.14–1.48) and 2.25 (95% CI: 1.96–2.59) for those with liver cirrhosis. Among patients who survived 30 days post-HF, the 31–365-day mortality was 18.5% among patients with noncirrhotic liver disease, 26.4% among patients with liver cirrhosis, and 19.4% among patients without liver disease. Corresponding crude and adjusted HRs were, respectively, 0.95 (95% CI: 0.86–1.04) and 1.08 (95% CI: 0.99–1.20) for patients with noncirrhotic liver disease and

Michael D Kappelman,1 Aksel Lange,2 Rachel L Randell,3 Patricia V Basta,4 Robert S Sandler,5 Kristina Laugesen,2 Anna Byrjalsen,2 Tina Christensen,2 Trine Frøslev,2 Rune Erichsen2,6 1Department of Pediatrics, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA; 2Department of Clinical Epidemiology,Aarhus University Hospital, Aarhus, Denmark; 3Department of Pediatrics, Duke University School of Medicine, Duke University, Durham, NC, USA; 4Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA; 5Department of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA; 6Surgical Department, Horsens Regional Hospital, Horsens, Denmark Background: Epidemiologic studies combining exposure and outcome data with the collection of biosamples are needed to study gene–environment interactions that might contribute to the etiology of complex diseases such as pediatric Crohn’s disease (CD). Nationwide registries, including those in Denmark and other Scandinavian countries, provide efficient and reliable sources of data for epidemiological studies evaluating the environmental determinants of disease. We performed a pilot study to test the feasibility of collecting salivary DNA to augment registry data in established cases of pediatric CD and randomly selected, population-based controls.Subjects and methods: Cases of CD born after 1995 and residing in the central region of Denmark were identified through the Danish National Patient Registry and confirmed by using standard diagnostic criteria. Age- and gender-matched controls were selected at random through the civil registration system. Cases and controls were contacted by mail and telephone and invited to submit a saliva sample. DNA was extracted and genotyped for six CD-associated single-nucleotide polymorphisms (SNPs).Results: A total of 53 cases of pediatric CD were invited, and 40 contributed a saliva sample (75% response rate

Background: The overall risk of cancer following ileal pouch-anal anastomosis [IPAA] is unknown, and pouch cancer surveillance is controversial. We evaluated long-term risk of cancer in a national cohort of patients with ulcerative colitis and IPAA, with emphasis on pouch cancer.Methods: Data on incident cancers were extracted from the national Danish Cancer Registry. Incidence rates for all site-specific cancers were compared between patients with IPAA and a gender- and age-matched comparison cohort from the background population to obtain incidence rate ratios [IRRs].Results: A total of 1723 patients with IPAA, operated for ulcerative colitis in the period 1980-2010, were matched to 8615 individuals from the background population. During a median follow-up of 12.9 years (interquartile range [IQR] 7.7-19.6 years), two pouch cancers [0.12%] were found after 16 and 27 years, respectively. In the population comparison cohort, 38 intestinal cancers [0.45%] were found, of which 35 were colorectal. The risk of hepatobiliary cancer was higher for patients with IPAA {IRR = 13.0 (95% confidence interval [CI]: 3.1-76.1)}, and half of the affected patients had coexisting primary sclerosing cholangitis. The risk of cancer overall following IPAA was identical to that of the comparison cohort: IRR = 1.05 [0.84-1.31].Conclusions: Pouch cancer following IPAA is very rare, questioning the need for general, rather than selective, surveillance. The overall cancer risk is comparable to that of the background population, and the increased risk of hepatobiliary cancer is likely an effect of coexisting liver disease and not causally related to IPAA.

PURPOSE: We aimed to investigate the prevalence and prognostic impact of tumor mesenchymal epithelial transition factor (MET) expression in stage IV gastric cancers in a real-world clinical setting because existing evidence is sparse.METHODS: The study included archived cancer specimens from 103 stage IV gastric cancer patients (2003-2010). We analyzed MET-protein expression by immunohistochemistry (MET-positive if ≥25% of tumor cells showed MET expression). We calculated overall survival using the Kaplan-Meier method and hazard ratios comparing mortality among MET-positive and MET-negative patients using Cox regression adjusted for age, gender, and comorbidity.RESULTS: We found that 62.1% (95% confidence interval, 52.0-71.5) of patients had MET-positive tumors. Median survival was lower among patients with MET-positive tumors (3.5 months) than among patients with MET-negative tumors (9.6 months), corresponding to an adjusted hazard ratio of 2.2 (95% confidence interval, 1.3-3.7).CONCLUSIONS: Tumor MET expression is prevalent and has substantial prognostic impact in stage IV gastric cancer patients.

BACKGROUND: The impact of surgical approach on the incidence of small bowel obstruction (SBO) is unclear. The aim of the current study was to analyze the long-term risk of surgery for SBO after open and laparoscopic surgery and to assess how subsequent SBO surgery impacts on mortality after colonic cancer resection.METHODS: This was a nationwide cohort study of patients undergoing elective colonic cancer resection with primary anastomosis in Denmark between 2001 and 2008. All included patients were operated with curative intent. Patients were identified in the Danish Colorectal Cancer Group database and followed through May 2014 in the Danish National Patient Register. The primary endpoint was surgery for SBO. Secondarily, mortality among patients who subsequently underwent SBO surgery and those who did not was compared.RESULTS: Among the 8583 included patients, 251 (2.9 %) underwent surgery for SBO during follow-up (median 8.8 years). The 3-year cumulative incidence of SBO surgery was 1.5 %; 1.2 % after laparoscopic and 1.6 % after open surgery. Laparoscopic surgery was associated with a decreased risk of SBO (hazard ratio [HR] 0.61 (CI 0.37 to 0.99, P = 0.048) compared with open surgery. The HR for mortality after colonic resection was 2.54 (CI 1.91 to 3.38, P < 0.001) for patients who underwent subsequent SBO surgery as compared to those who did not.CONCLUSIONS: Laparoscopic surgery for colonic cancer was associated with a decreased risk of subsequent SBO surgery compared with open surgery. Further, subsequent SBO surgery was associated with increased mortality after colonic cancer resection.

Ane Birgitte Telén Andersen,1 Rune Erichsen,1 Michael David Kappelman,2 Trine Frøslev,1 Vera Ehrenstein1 1Department of Clinical Epidemiology, Aarhus University Hospital, Aarhus, Denmark; 2Department of Pediatrics, Division of Pediatric Gastroenterology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA Objective: The incidences of celiac disease (CD) and asthma are increasing and the two conditions are associated in individuals. Risk of asthma may be passed on to the next generation through shared risk factors. We examined whether parental CD is associated with risk of asthma in offspring. Methods: We conducted a population-based Danish nationwide cohort study, using medical databases, covering the period 1 January 1979 to 31 December 2009. For each child with a parental history of CD, we randomly sampled 100 children without this history from the children born in the same calendar year. We used Cox proportional-hazards regression to estimate incidence rate ratios for asthma, adjusting for measured covariates. Results: We identified 1,107 children with a parental history of CD and 110,700 children without this parental history. During up to 32 years of follow-up, 6,125 children received a hospital diagnosis of asthma. The adjusted incidence rate ratio for asthma associated with a parental history of CD was 1.09 (95% confidence interval: 0.86–1.39) and was similar for maternal and paternal CD. Inclusion of asthma-medication in the definition of asthma did not substantially change the results. Conclusion: There was no convincing evidence of an increased risk of asthma among offspring of parents with CD. Keywords: asthma, celiac disease, children, cohort study, parents

AIMS: Inflammation is considered to play a role in the development of atrial fibrillation (AF). Hence inflammatory bowel disease (IBD) may be associated with AF. We therefore examined the incidence of AF and stroke in patients with IBD.METHODS AND RESULTS: From Danish nationwide registries 1996-2011, we identified 24 499 patients with new-onset IBD and 236 275 age- and sex-matched controls. Poisson regression analyses with continuously updated covariates were used to estimate incidence rate ratios (IRRs) of AF and stroke. Disease activity stages of flare (new disease activity), persistent activity, and remission were defined by corticosteroid prescriptions, IBD hospital admissions, and biological treatment. Inflammatory bowel disease patients had a mean age of 43.9 years, 53.9% were women, and mean follow-up was 6.8 years. Among IBD patients, 685 had AF and 549 had a stroke, corresponding to incidence rates per 1000 person-years of 4.16 vs. 2.70 for AF and 3.33 vs. 2.44 for stroke, compared with matched controls. Overall IBD-associated risk of AF corresponded to IRR 1.26 (1.16-1.36), but was driven by increased AF incidence during IBD flares [IRR 2.63 (2.26-3.06)] and persistent activity [IRR 2.06 (1.67-2.55)], whereas no increased AF risk was observed in remission periods [IRR 0.97 (0.88-1.08)]. Likewise increased stroke risk was exclusively found during active IBD [IRRs: 1.57 (1.27-1.93), 1.71 (1.32-2.21), and 1.04 (0.93-1.15) for flares, persistent activity, and remission, respectively].CONCLUSION: Active IBD is associated with increased risk of AF and stroke. These findings may be relevant to clinical practice.

BACKGROUND: Inflammatory bowel disease (IBD) has been linked to adverse cardiovascular events, but a relation to heart failure (HF) is uncertain. We investigated the IBD-associated risk of HF in a nationwide setting.METHODS AND RESULTS: A total of 5 436 647 Danish citizens, with no history of IBD or HF, were included on January 1, 1997, and followed up until first hospitalization for HF, death, or December 31, 2011. Of these subjects, 23 681 developed IBD for which disease activity was determined continuously throughout the study. The risk of hospitalization for HF was estimated with a Poisson regression model adjusting for comorbidity and cardiovascular pharmacotherapy as time-dependent covariates. During a mean follow-up of 11.8 years in the reference population and 6.4 years in the IBD group, hospitalization for HF occurred in 553 subjects with IBD and 171 405 in the reference population. Patients with IBD had a 37% increased risk of hospitalization for HF (incidence rate ratio, 1.37; 95% confidence interval, 1.26-1.49) compared with the reference population. IBD activity-specific analyses showed markedly increased risk of HF hospitalization during flares (incidence rate ratio, 2.54; 95% confidence interval, 2.13-3.04) and persistent activity (incidence rate ratio, 2.73; 95% confidence interval, 2.25-3.33) but not in IBD remission (incidence rate ratio, 1.04; 95% confidence interval, 0.94-1.16).CONCLUSIONS: In a nationwide cohort, IBD was associated with an increased risk of hospitalization for HF, and this risk was strongly correlated to periods of active disease. The mechanisms underlying this finding warrant further studies.

BACKGROUND: Inflammatory bowel disease (IBD) is associated with increased cardiovascular risk. We examined the effect of active IBD on major adverse cardiovascular outcomes after myocardial infarction (MI).METHODS AND RESULTS: In nationwide registries, we identified 86 790 patients with first-time MI from the period 2002 to 2011. A total of 1030 patients had IBD, and we categorized their disease activity stages into either flare (120 days), persistent (>120 days) activity, or remission. Short-term mortality was estimated in a logistic regression-model, whereas risk of recurrent MI, all-cause mortality, and a composite of recurrent MI, cardiovascular death, and stroke were estimated by Cox regression-models. Odds ratio of death during hospitalization or within 30 days of discharge (n=13 339) corresponded to 3.29 (95% confidence interval [CI], 1.98-5.45) for patients in IBD flares, 1.62 (95% CI, 0.95-2.77) for persistent activity, and 0.97 (95% CI, 0.78-1.19) for remission when compared with the non-IBD group. Among 73 451 patients, including 863 with IBD, alive 30 days after discharge, IBD was associated with hazard ratios of 1.21 (95% CI, 0.99-1.49) for recurrent MI, 1.14 (95% CI, 1.01-1.28) for all-cause mortality, and 1.17 (95% CI, 1.03-1.34) for the composite end point. When compared with the non-IBD group, IBD flares, in particular, were associated with increased risks of recurrent MI (hazard ratio, 3.09; 95% CI, 1.79-5.32), all-cause mortality (hazard ratio, 2.25; 95% CI, 1.61-3.15), and the composite end point (hazard ratio, 2.04; 95% CI, 1.35-3.06), whereas no increased risk was identified in remission.CONCLUSIONS: Active inflammatory bowel disease worsens prognosis after MI, in particular, in relation with flares.

AIMS: Inflammation is considered to play a role in the development of atrial fibrillation (AF). Hence inflammatory bowel disease (IBD) may be associated with AF. We therefore examined the incidence of AF and stroke in patients with IBD.METHODS AND RESULTS: From Danish nationwide registries 1996-2011, we identified 24 499 patients with new-onset IBD and 236 275 age- and sex-matched controls. Poisson regression analyses with continuously updated covariates were used to estimate incidence rate ratios (IRRs) of AF and stroke. Disease activity stages of flare (new disease activity), persistent activity, and remission were defined by corticosteroid prescriptions, IBD hospital admissions, and biological treatment. Inflammatory bowel disease patients had a mean age of 43.9 years, 53.9% were women, and mean follow-up was 6.8 years. Among IBD patients, 685 had AF and 549 had a stroke, corresponding to incidence rates per 1000 person-years of 4.16 vs. 2.70 for AF and 3.33 vs. 2.44 for stroke, compared with matched controls. Overall IBD-associated risk of AF corresponded to IRR 1.26 (1.16-1.36), but was driven by increased AF incidence during IBD flares [IRR 2.63 (2.26-3.06)] and persistent activity [IRR 2.06 (1.67-2.55)], whereas no increased AF risk was observed in remission periods [IRR 0.97 (0.88-1.08)]. Likewise increased stroke risk was exclusively found during active IBD [IRRs: 1.57 (1.27-1.93), 1.71 (1.32-2.21), and 1.04 (0.93-1.15) for flares, persistent activity, and remission, respectively].CONCLUSION: Active IBD is associated with increased risk of AF and stroke. These findings may be relevant to clinical practice.

BACKGROUND: Inflammatory bowel disease (IBD) has been linked to adverse cardiovascular events, but a relation to heart failure (HF) is uncertain. We investigated the IBD-associated risk of HF in a nationwide setting.METHODS AND RESULTS: A total of 5 436 647 Danish citizens, with no history of IBD or HF, were included on January 1, 1997, and followed up until first hospitalization for HF, death, or December 31, 2011. Of these subjects, 23 681 developed IBD for which disease activity was determined continuously throughout the study. The risk of hospitalization for HF was estimated with a Poisson regression model adjusting for comorbidity and cardiovascular pharmacotherapy as time-dependent covariates. During a mean follow-up of 11.8 years in the reference population and 6.4 years in the IBD group, hospitalization for HF occurred in 553 subjects with IBD and 171 405 in the reference population. Patients with IBD had a 37% increased risk of hospitalization for HF (incidence rate ratio, 1.37; 95% confidence interval, 1.26-1.49) compared with the reference population. IBD activity-specific analyses showed markedly increased risk of HF hospitalization during flares (incidence rate ratio, 2.54; 95% confidence interval, 2.13-3.04) and persistent activity (incidence rate ratio, 2.73; 95% confidence interval, 2.25-3.33) but not in IBD remission (incidence rate ratio, 1.04; 95% confidence interval, 0.94-1.16).CONCLUSIONS: In a nationwide cohort, IBD was associated with an increased risk of hospitalization for HF, and this risk was strongly correlated to periods of active disease. The mechanisms underlying this finding warrant further studies.

BACKGROUND: Inflammatory bowel disease (IBD) is associated with increased cardiovascular risk. We examined the effect of active IBD on major adverse cardiovascular outcomes after myocardial infarction (MI).METHODS AND RESULTS: In nationwide registries, we identified 86 790 patients with first-time MI from the period 2002 to 2011. A total of 1030 patients had IBD, and we categorized their disease activity stages into either flare (120 days), persistent (>120 days) activity, or remission. Short-term mortality was estimated in a logistic regression-model, whereas risk of recurrent MI, all-cause mortality, and a composite of recurrent MI, cardiovascular death, and stroke were estimated by Cox regression-models. Odds ratio of death during hospitalization or within 30 days of discharge (n=13 339) corresponded to 3.29 (95% confidence interval [CI], 1.98-5.45) for patients in IBD flares, 1.62 (95% CI, 0.95-2.77) for persistent activity, and 0.97 (95% CI, 0.78-1.19) for remission when compared with the non-IBD group. Among 73 451 patients, including 863 with IBD, alive 30 days after discharge, IBD was associated with hazard ratios of 1.21 (95% CI, 0.99-1.49) for recurrent MI, 1.14 (95% CI, 1.01-1.28) for all-cause mortality, and 1.17 (95% CI, 1.03-1.34) for the composite end point. When compared with the non-IBD group, IBD flares, in particular, were associated with increased risks of recurrent MI (hazard ratio, 3.09; 95% CI, 1.79-5.32), all-cause mortality (hazard ratio, 2.25; 95% CI, 1.61-3.15), and the composite end point (hazard ratio, 2.04; 95% CI, 1.35-3.06), whereas no increased risk was identified in remission.CONCLUSIONS: Active inflammatory bowel disease worsens prognosis after MI, in particular, in relation with flares.

Ane Birgitte Telén Andersen, Vera Ehrenstein, Rune Erichsen, Trine Frøslev, Henrik Toft Sørensen Department of Clinical Epidemiology, Aarhus University Hospital, Aarhus, Denmark Purpose: Inflammatory bowel disease (IBD) and autism spectrum disorders (ASD) may share genetic and environmental risk factors. We examined whether parental IBD is associated with an increased risk of ASD in offspring. Methods: We conducted a registry-based nationwide cohort study including children born alive in Denmark from January 1, 1994 to December 31, 2009, with follow-up throughout 2010. IBD in parents and ASD in offspring were identified using inpatient and outpatient hospital diagnoses. We computed risk of ASD and crude and adjusted incidence rate ratios (aIRRs) with 95% confidence intervals (CI) using Cox proportional-hazards regression. We evaluated the risk of ASD according to maternal and paternal IBD, and separately for maternal and paternal Crohn's disease (CD) and ulcerative colitis (UC). Children with parents free of IBD were the comparison cohort. Results: We identified 1,005,330 children during the study period. Among them, 11,888 (1.2%) had a parent with IBD and 8,087 (0.8%) had a diagnosis of ASD during up to 17 years of follow-up. The 10-year risks of ASD were 0.7% among children of parents with IBD and 0.9% among children of parents without IBD. The aIRR for ASD among children with parental IBD was 0.8 (95% CI: 0.6–1.0), and results were similar regardless of parent of IBD origin or whether a parent had CD or UC. The estimates were similar for different ASD subtypes. Conclusion: We found no evidence of an increased risk of ASD among children born to parents with IBD. Keywords: autistic disorder, children, cohort study, epidemiology, inflammatory bowel disease, parents

Jennifer L Lund,1 Trine Frøslev,1 Thomas Deleuran,1,2 Rune Erichsen,1 Tove Nilsson,1 Annette Nørkær Pedersen,3 Morten Høyer4 1Department of Clinical Epidemiology, 2Department of Medicine V (Hepatology and Gastroenterology), 3Hospital Pharmacy, 4Department of Oncology, Aarhus University Hospital, Aarhus, Denmark Background: The Danish National Registry of Patients (DNRP) is a potentially valuable resource for monitoring national trends in the use of chemotherapy and evaluating the benefits and harms of alternative treatments among colorectal cancer (CRC) patients in Denmark. However, the validity of chemotherapy reporting in the DNRP is unknown. In this study, we evaluated the validity of the DNRP for identifying the receipt of chemotherapy and specific treatments, and the timing and number of treatments among CRC patients, using medical records and pharmacy data as the reference standard. Methods: We selected a random sample of CRC patients with lymph node involvement who were diagnosed at Aarhus University Hospital (n = 25) or Aalborg University Hospital (n = 25) from 2009 to 2010. Administration dates, specific treatments, and number of treatment courses were abstracted for the 180 days post diagnosis from the DNRP, medical records, and pharmacy production databases. The prevalence of chemotherapy, timing of first administration, and number of courses were described. DNRP data were compared with the reference standard for each hospital, and the kappa, sensitivity, specificity, positive and negative predictive values, and 95% confidence intervals were calculated for the receipt of any chemotherapy and specific treatments. Results: The prevalence of chemotherapy was 72% and 68% among CRC patients treated in Aarhus and Aalborg, respectively, with >90% of patients without distant metastasis receiving treatment within 90 days from diagnosis. Patients received on average 4.6 and 4.7 treatment courses in Aarhus and Aalbor

Chronic inflammatory diseases have been linked to increased risk of atherothrombotic events, but the risk associated with inflammatory bowel disease (IBD) is unclear. We therefore examined the risk of myocardial infarction (MI), stroke, and cardiovascular death in patients with IBD.

Chronic inflammatory diseases have been linked to increased risk of atherothrombotic events, but the risk associated with inflammatory bowel disease (IBD) is unclear. We therefore examined the risk of myocardial infarction (MI), stroke, and cardiovascular death in patients with IBD.

Inès Ben Ghezala, Johan Frederik Berg Arendt, Rune Erichsen, Jihen Zalfani, Henrik Gammelager, Trine Frøslev, Morten OlsenDepartment of Clinical Epidemiology, Aarhus University Hospital, Aarhus, DenmarkPurpose: The aim of this validation study was to assess the positive predictive value (PPV) of the International Classification of Diseases, 10th revision (ICD-10) diagnosis of vitamin B12 (cobalamin [Cbl]) deficiency anemia in the Danish National Patient Register (DNPR).Patients and methods: We identified all patients above 18 years of age recorded in the DNPR with a diagnosis of Cbl deficiency anemia (ICD-10 code: D51) admitted to two Danish university hospitals and one Danish regional hospital from 2000 through 2009. We assessed the PPV using biochemical parameters on Cbl deficiency with or without anemia as reference standards. These data were obtained from the Laboratory Information Systems Database. Data on prescriptions with Cbl supplementation drugs were obtained from the Aarhus University Prescription Database.Results: We identified 1089 patients coded with a Cbl deficiency anemia diagnosis in the DNPR. The PPV was 31.5% (95% confidence interval [CI]: 28.8%–34.3%) and 36.8% (95% CI: 34.0%–39.7%) depending on definitions of Cbl deficiency with anemia. When using Cbl deficiency without anemia as a reference standard, the PPV was 51.3% (95% CI: 48.4%–54.3%). The PPV for Cbl supplemented patients was 22.2% (95% CI: 18.0%–26.9%) and for non-Cbl supplemented patients 63.9% (95% CI: 60.5%–67.3%).Conclusion: The PPVs of the ICD-10 diagnosis coding for Cbl deficiency anemia were generally low in the DNPR. Therefore, this register should be used with caution to study patients with Cbl deficiency anemia.Keywords: vitamin B12 deficiency anemia, Danish National Patient Register, Laboratory Information Systems Database, International Classification of Diseases, positive predictive value, validation stu

Jihen Zalfani, Trine Frøslev, Morten Olsen, Inès Ben Ghezala, Henrik Gammelager, Johan FB Arendt, Rune ErichsenDepartment of Clinical Epidemiology, Aarhus University Hospital, Aarhus, DenmarkObjective: Valid data on anemia caused by bleeding are needed for epidemiological research and monitoring health care. The Danish National Registry of Patients (DNRP) is a nationwide medical database with information on all Danish residents' hospital history. We aimed to assess the positive predictive value (PPV) of the diagnostic coding of anemia caused by bleeding in the DNRP.Methods: In the DNRP, we identified all patients with International Classification of Disease, 10th edition codes for anemia caused by bleeding (acute: D50.0; chronic: D62.6) at three Danish hospitals from 2000 through 2009. For these patients we computed the PPV using hemoglobin level data, from Aarhus University laboratory database, as reference standard. Anemia was defined by a hemoglobin level less than 7.0 mmol/L for women and less than 8.0 mmol/L for men.Results: We identified 3391 patients in the DNRP with a diagnosis of anemia caused by bleeding. The overall PPV was 95.4% (95% confidence interval [CI]: 94.6%–96.0%). The PPV was 97.6% (95% CI: 96.6%–98.3%) for men and 94.0% (95% CI: 92.9%–94.9%) for women, and the PPV increased with age at diagnosis. The PPV varied according to type of discharging departments, from 89.2% (95% CI: 83.4%–93.4%) in gynecology to 96.8% (95% CI: 94.9%–98.2%) in surgery, and was lower for outpatients compared with inpatients.Conclusion: We found a high PPV of the coding for anemia caused by bleeding in the DNRP. The registry is a valid source of data on anemia caused by bleeding for various purposes including research and monitoring health care.Keywords: anemia, Danish National Registry of Patients, International Classification of Diseases, predictive value, laboratory database, validation

Malene Schou Nielsson,1 Rune Erichsen,1 Trine Frøslev,1 Aliki Taylor,2 John Acquavella,2 Vera Ehrenstein11Department of Clinical Epidemiology, Aarhus University Hospital, Aarhus, Denmark; 2Center for Observational Research International, Amgen Ltd Thousand Oaks, CA, USA Background: The purpose of this study was to estimate the positive predictive value (PPV) of the coding for bisphosphonate treatment in selected cancer patients from the Danish National Patient Registry (DNPR).Methods: Through the DNPR, we identified all patients with recorded cancer of the breast, prostate, lung, kidney, and with multiple myeloma. We restricted the study sample to patients with bisphosphonate treatment recorded during an admission to Aalborg Hospital, Denmark, from 2005 through 2009. We retrieved and reviewed medical records of these patients from the initial cancer diagnosis onwards to confirm or rule out bisphosphonate therapy. We calculated the PPV of the treatment coding as the proportion of patients with confirmed bisphosphonate treatment.Results: We retrieved and reviewed the medical records of 60 cancer patients with treatment codes corresponding to bisphosphonate therapy. Recorded code corresponded to treatment administered intravenously for 59 of 60 patients, corresponding to a PPV of 98.3% (95% confidence interval 92.5–99.8). In the remaining patient, bisphosphonate treatment was also confirmed but was an orally administered bisphosphonate; thus, the treatment for any bisphosphonate regardless of administration was confirmed for all 60 patients (PPV of 100%, 95% confidence interval 95.9–100.0).Conclusion: The PPV of bisphosphonate treatment coding among cancer patients in the DNPR is very high and the recorded treatment nearly always corresponds to intravenous administration.Keywords: bisphosphonate, neoplasm metastases, predictive value of tests, validation studies

Ane Birgitte Telén Andersen, Dóra Körmendiné Farkas, Frank Mehnert, Vera Ehrenstein, Rune ErichsenDepartment of Clinical Epidemiology, Aarhus University Hospital, DenmarkPurpose: Use of paracetamol during pregnancy may increase the risk of asthma in offspring. The association between prenatal exposure to maternal use of paracetamol and risk of asthma was investigated.Methods: A cohort study of 197,060 singletons born in northern Denmark in 1996–2008 was conducted, with follow-up until the end of 2009. Maternal paracetamol use during pregnancy was defined as a redeemed prescription. Asthma in offspring was defined as at least two prescriptions of both a β-agonist and an inhaled glucocorticoid and/or a hospital diagnosis of asthma during follow-up. Absolute risk of asthma in offspring was estimated using the Kaplan–Meier method and incidence rate ratios adjusted for known risk factors were estimated using Cox proportional-hazards regression.Results: Overall, 976 (0.5%) children were exposed prenatally to maternal use of prescription paracetamol. During follow-up, 24,506 (12.4%) children developed asthma. Absolute risk of asthma was 7.5% after 2 years and 14.4% after 10 years among the unexposed children. Corresponding risks were 12.7% and 21.6% among the exposed children. The adjusted incidence rate ratio was 1.35 (95% confidence interval: 1.17–1.57) for exposure in any trimester of pregnancy. A similar association was present for paracetamol exposure in each of the trimesters and for maternal use of prescription nonsteroidal anti-inflammatory drugs. Furthermore, maternal prescription use in the year following the relevant delivery also showed similar associations.Conclusion: A robust association was found between prenatal exposure to maternal use of prescription paracetamol and the risk of asthma; however, noncausal explanations could not be ruled out for such association.Keywords: aceta

Jonathan Montomoli,1 Stephen Jacques Hamilton-Dutoit,2 Trine Frøslev,1 Aliki Taylor,3 Rune Erichsen11Department of Clinical Epidemiology, Aarhus University Hospital, Aarhus, Denmark; 2Institute of Pathology, Aarhus University Hospital, Aarhus, Denmark; 3Centre for Observational Research, Amgen, Uxbridge, UKBackground: The occurrence of KRAS mutations and their association with prognosis in metastatic colorectal cancer patients is not well documented in population-based studies.Objectives: To examine the feasibility of identifying archived colorectal cancer specimens, and through linkage with nationwide Danish population-based databases to investigate the prevalence of KRAS mutations and their association with colorectal cancer survival.Methods: We used the Danish Pathology Database to identify the physical location of primary (or in some cases secondary) tumor specimens from selected metastatic colorectal cancer patients referred to our hospital for palliative chemotherapy between November 1, 2008 and September 30, 2009. Routinely stored paraffin tissue blocks were obtained from the pathology archives of the originating hospital. KRAS mutation tumor status was assessed for each patient using the commercialized TheraScreen KRAS Mutation Kit. Using the unique identifier number, we linked the patients to the Danish National Registry of Patients and the Danish Civil Registration System to obtain data on date of first colorectal cancer diagnosis and follow-up status. We estimated prevalence of KRAS mutations and the 1-, 2-, and 5-year survival after colorectal cancer diagnosis using the Kaplan–Meier technique.Results: We identified 106 metastatic colorectal cancer patients (64% males). All were successfully linked to the registries, and archived tumor-tissue samples were obtained and analyzed in each case. The overall prevalence of KRAS mutations was 55%, and 1-, 2-, and 5-year overall survival after colorectal cancer diagnosis was 91%, 68%, and 25%