Evaluation of Left Truncation and Censoring When Changing the Use of the International Classification of Diseases Eighth Revision Codes to Tenth Revision Codes in the Danish National Patient Registry.

Purpose: In the Danish National Patient Registry (DNPR), covering all Danish hospitals and widely used in research, diseases have been recorded using International Classification of Diseases (ICD) codes, transitioning from the Eighth to the Tenth revision in 1994. Uncertainty exists regarding whether including ICD-8 codes alongside ICD-10 is needed for complete disease identification. We assessed the extent of left-truncation and left-censoring in the DNPR arising from omitting ICD-8 codes. Patients and Methods: We sampled 500,000 Danes ≥40 years of age in 1995, 2010, and 2018. From the DNPR, we identified cardiovascular, endocrine, gastrointestinal, neurological, pulmonary, rheumatic, and urogenital diseases as well as fractures. We obtained the number of people with a disease recorded with ICD-8 codes only (ie, the ICD-8 record would be left-truncated by not using ICD-8 codes), ICD-8 plus ICD-10 codes (ie, the ICD-8 record would be left-censored by not using ICD-8 codes), and ICD-10 codes only. For each ICD group, we calculated the proportion of people with the disease relative to the total sample (ie, 500,000 people) and the total number of people with the disease across all ICD groups. Results: Overall, the left-truncation issue decreased over the years. Relative to all people with a disease, the left-truncated proportion was for example 59% in 1995 and <2% in 2018 for diabetes mellitus; 93% in 1995, and 54% in 2018 for appendicitis. The left-truncation issue increased with age group for most diseases. The proportion of disease records left-censored by not using ICD-8 codes was generally low but highest for chronic diseases. Conclusion: The left-truncation issue diminished over sample years, particularly for chronic diseases, yet remained rather high for selected surgical diseases. The left-truncation issue increased with age group for most diseases. Left-censoring was overall a minor issue that primarily concerned chronic diseases.

Short-term outcomes following total colectomy for inflammatory bowel disease in Denmark after implementation of laparoscopy: a nationwide population-based study.

AIM: A laparoscopic approach to total colectomy (TC) for inflammatory bowel disease (IBD) is being increasingly used, but data on its comparative benefits over open TC are conflicting. The aim of this study was to examine 90-day outcomes following laparoscopic and open TC for IBD in a nationwide cohort after the introduction of laparoscopy. METHOD: IBD patients undergoing TC in Denmark from 2005 to 2017 were identified from the Danish National Patient Registry. We used Kaplan-Meier methodology to estimate mortality and Cox regression analysis to estimate adjusted mortality rate ratios (aMRRs) and adjusted hazard ratios (aHRs) of reoperation, readmission and intensive care unit (ICU) transfer, comparing patients undergoing laparoscopic versus open TC. RESULTS: We identified 1095 patients undergoing laparoscopic TC and 1523 patients undergoing open TC. Following emergency TC, 90-day mortality was 2.8% (1.6%-4.9%) after laparoscopic TC and 9.1% (7.0%-11.8%) after open TC. Ninety-day mortality was 0.9% (0.3%-2.5%) after laparoscopic TC and 2.6% (1.5%-4.3%) after open elective TC. The aMRRs associated with laparoscopic TC were 0.45 (95% CI 0.25-0.80) in emergency cases and 0.29 (95% CI 0.10-0.86) in elective cases. Risks of readmission were comparable following laparoscopic versus open TC, both in emergency [aHR = 0.93 (95% CI 0.76-1.15)] and elective [aHR = 0.83 (95% CI 0.68-1.02)] cases, while risks of ICU transfer and reoperation were lower following laparoscopic TC, both in emergency cases [aHR = 0.53 (95% CI 0.35-0.82) and aHR = 0.26 (95% CI 0.15-0.47)] and elective [aHR = 0.58 (95% CI 0.35-0.95) and aHR = 0.37 (95% CI 0.21-0.66)] cases. CONCLUSION: The introduction of laparoscopic TC for IBD in Denmark was not associated with increased mortality or morbidity. In fact, laparoscopic TC for IBD may be associated with lower short-term mortality and morbidity compared with open TC.

Non-Traumatic Subdural Hematoma and Cancer: A Cohort Study.

Introduction: Cancer may increase the risk of bleeding. However, whether subdural hematoma is a marker of occult cancer remains unknown. We examined the association between non-traumatic subdural hematoma and cancer risk in a cohort study. Materials and Methods: Using Danish nationwide health registries, we identified 2713 patients with non-traumatic subdural hematoma and no previous cancer diagnosis, who were hospitalized between April 1, 1996 and December 31, 2019. We computed age-, sex-, and calendar year-standardized incidence ratios (SIRs) as the ratio of the observed to expected number of patients with cancer by using national incidence rates as reference as a measure of relative risk. Results: We identified 77 cancer cases within the first year of follow-up and 272 cancer cases thereafter. The one-year risk of cancer was 2.8% (95% confidence interval: 2.2-3.5), and the one-year SIR was 1.7 (95% confidence interval: 1.3-2.1). During the subsequent years, the SIR was 1.0 (95% confidence interval: 0.9-1.1). The relative risk was elevated for some hematological and liver cancers. Conclusion: The risk of a new cancer diagnosis was clearly increased in patients with non-traumatic subdural hematoma compared with the general population during the first year of follow-up. However, the absolute risk was low, thus limiting the clinical relevance of pursuing early cancer detection in these patients.

Root-cause Analysis of 762 Danish Post-colonoscopy Colorectal Cancer Patients.

BACKGROUND & AIMS: The term post-colonoscopy colorectal cancer (PCCRC) refers to colorectal cancer (CRC) diagnosed after a negative colonoscopy. Using the root-cause algorithm proposed by the World Endoscopy Organization, we aimed to investigate plausible explanations for PCCRCs and potential changes in plausible explanations for PCCRCs over time in a Danish Region. METHODS: During 1995 to 2021, we used national health registries and electronic medical records in the Central Denmark Region to identify PCCRC cases, defined as CRCs recorded within 6 to 48 months after a colonoscopy. We then applied the World Endoscopy Organization algorithm to categorize explanations for PCCRC as follows: (A) possible missed lesion, prior examination adequate; (B) possible missed lesion, prior examination inadequate; (C) detected lesion, not resected; or (D) likely incomplete resection of previously identified lesion. PCCRCs were identified before (1995-2013) and after (2014-2021) implementation of nationwide fecal immunochemical test-based CRC screening and quality indicators for colonoscopy. RESULTS: We identified 762 PCCRCs, 53.5% among males and 57% among individuals ≥70 years. Forty-five percent were located in the proximal colon. We identified 616 (80.8%; 95% confidence interval [CI], 74.6%-87.5%) category A PCCRCs; 36 (4.7%; 95% CI, 3.3%-6.5%) category B PCCRCs; 26 (3.4%; 95% CI, 2.2%-4.9%) category C PCCRCs; and 84 (11%; 95% CI, 8.8%-13.6%) category D PCCRCs. Similar patterns were observed during the early (1995-2013) and late (2014-2021) study periods. CONCLUSIONS: Most PCCRCs originate from possible missed lesions and incompletely resected lesions during the complete study period. These findings indicate the importance of quality assurance of colonoscopy procedures and polypectomy techniques.

Health registries as research tools: a review of methodological key issues.

Health registries provide opportunities for conducting large-scale, population-based studies, but attention must be devoted to their specific limitations. Herein, we describe potential limitations that may affect the validity of registry-based research. Our review includes descriptions of 1) populations, 2) variables, 3) medical coding systems for medical information and 4) selected key methodological challenges. Knowledge of such factors and epidemiological study designs in general is likely to increase the quality of registry-based research and reduce potential biases.

Maternal Smoking During Pregnancy and Risk of Appendicitis in the Offspring.

BACKGROUND: Existing evidence on the link between smoking and appendicitis is scarce and ambiguous. We therefore conducted a population-based cohort study in Denmark to investigate whether smoking during pregnancy is associated with an increased risk of appendicitis in offspring. METHODS: We used the Danish Birth Registry to include all singletons born during 1991-2017 and to identify maternal smoking status during pregnancy. We followed the children from birth until date of appendicitis, emigration, death, or administrative end of study (31 December 2018), whichever came first. We calculated crude and adjusted hazard ratios (HRs) of appendicitis with 95% confidence intervals (CIs) comparing children of mothers who smoked during pregnancy to children of nonsmokers. Further, we conducted a bias analysis and sibling analysis. RESULTS: We included 1,659,526 singletons of whom 19% were born to mothers who smoked during pregnancy. After maximum 28 years of follow-up, hazard rates for children of smokers were slightly higher than for children of nonsmokers [adjusted HR: 1.07 (95% CI = 1.04, 1.10)]. Stratification by sex revealed no association for males [adjusted HR: 1.02 (95% CI = 0.99, 1.06)], but a higher HR for females [adjusted HR: 1.13 (95% CI = 1.09, 1.18)]. This association increased with increasing length of follow-up, indicating that the association may be mediated by later-life exposures. The bias analysis indicated that misclassification of maternal smoking could attenuate a true association, while the sibling analysis showed no association. CONCLUSIONS: Maternal smoking during pregnancy and appendicitis in the offspring may be associated.

A Review of Major Danish Biobanks: Advantages and Possibilities of Health Research in Denmark.

Biobank research may lead to an improved understanding of disease etiology and advance personalized medicine. Denmark (population ~5.9 million) provides a unique setting for population-based health research. The country is a rich source of biobanks and the universal, tax-funded healthcare system delivers routinely collected data to numerous registries and databases. By virtue of the civil registration number (assigned uniquely to all Danish citizens), biological specimens stored in biobanks can be combined with clinical and demographic data from these population-based health registries and databases. In this review, we aim to provide an understanding of advantages and possibilities of biobank research in Denmark. As knowledge about the Danish setting is needed to grasp the full potential, we first introduce the Danish healthcare system, the Civil Registration System, the population-based registries, and the interface with biobanks. We then describe the biobank infrastructures, comprising the Danish National Biobank Initiative, the Bio- and Genome Bank Denmark, and the Danish National Genome Center. Further, we briefly provide an overview of fourteen selected biobanks, including: The Danish Newborn Screening Biobank; The Danish National Birth Cohort; The Danish Twin Registry Biobank; Diet, Cancer and Health; Diet, Cancer and Health - Next generations; Danish Centre for Strategic Research in Type 2 Diabetes; Vejle Diabetes Biobank; The Copenhagen Hospital Biobank; The Copenhagen City Heart Study; The Copenhagen General Population Study; The Danish Cancer Biobank; The Danish Rheumatological Biobank; The Danish Blood Donor Study; and The Danish Pathology Databank. Last, we inform on practical aspects, such as data access, and discuss future implications.

Increased Cancer Risk in Patients with Kidney Disease and Venous Thromboembolism: A Population-Based Cohort Study.

BACKGROUND: Venous thromboembolism (VTE) may be a harbinger of cancer in the general population. Patients with kidney disease have an a priori increased VTE risk. However, it remains unknown how a VTE affects subsequent cancer risk in these patients. OBJECTIVES: To examine the cancer risk in patients with kidney disease following a VTE. METHODS: We conducted a nationwide population-based cohort study in Denmark (1996-2017), including all VTE patients with a diagnosis of kidney disease. We calculated absolute risks of cancer (accounting for competing risk of death) and age-, sex-, and calendar-period standardized incidence ratios (SIRs) comparing the observed cancer incidence with national cancer incidence rates and cancer incidence rates of VTE patients without kidney disease. RESULTS: We followed 3,362 VTE patients with kidney disease (45.9% females) for a median follow-up time of 2.4 years (interquartile range: 0.6-5.4). During follow-up, 464 patients were diagnosed with cancer, of whom 169 (36.4%) were diagnosed within the first year. The 1-year absolute risk of any cancer was 5.0% (95% confidence interval [CI]: 4.3-5.8), with a SIR of 2.9 (95% CI: 2.5-3.4) when compared with the general population, and 2.0 (95% CI: 1.8-2.4) when compared with VTE patients without kidney disease. During subsequent years of follow-up, the SIRs declined to 1.5 (95% CI: 1.3-1.6) when compared with the general population, and 1.1 (95% CI: 0.9-1.2) compared with VTE patients without kidney disease. CONCLUSION: Patients with hospital-diagnosed kidney disease have increased cancer risk after VTE, especially within the first year following the VTE diagnosis.

Risk of dementia in patients with inflammatory bowel disease: a Danish population-based study.

BACKGROUND: Inflammatory bowel disease (IBD) may be associated with increased dementia risk, but the literature is conflicting. AIM: To investigate dementia risk in patients with IBD. METHODS: We conducted a nationwide population-based cohort study in Denmark (1977-2018) including all patients with incident IBD matched with up to 10 general population comparators without IBD by sex, year of birth and region of residence. We calculated cumulative incidence proportions (CIPs) of dementia treating death as a competing risk, and adjusted hazard ratios (HRs) comparing IBD patients with matched comparisons. In a nested case-control analysis, we investigated the impact of IBD severity, steroid use, colorectal and small bowel surgery, and healthcare system contacts on dementia risk. RESULTS: Of 88,985 patients with IBD (69.6% with ulcerative colitis [UC], 30.4% with Crohn's disease [CD]) and 884,108 comparisons, 2076 patients (78.1% with UC) and 23,011 comparisons (76.6% UC comparisons) developed dementia. The 40-year CIP of all-cause dementia was 7.2% for UC patients and 5.8% for CD patients. UC patients had a slightly increased HR of all-cause dementia (HR = 1.07 [95% confidence interval (CI): 1.01;1.12]) and Alzheimer's disease (HR = 1.10 [95% CI: 1.01-1.19]). CD patients had an increased HR of all-cause dementia (HR = 1.15 [95% CI: 1.05-1.27]) and frontotemporal dementia (HR = 2.70 [95% CI: 1.44-5.05]). Dementia in IBD patients was associated with frequent healthcare system contacts. CONCLUSIONS: UC and CD are associated with slightly increased all-cause dementia risk, particularly frontotemporal dementia in CD patients. Frequent healthcare system contacts by patients with IBD and detection bias may play a role in the association.

Risk of a post-colonoscopy colorectal cancer in patients with type 2 diabetes: a Danish population-based cohort study.

OBJECTIVE: Prevalent type 2 diabetes (T2D) is associated with an increased risk of colorectal cancer and could impair the quality of bowel preparation for colonoscopy. This may in turn increase the risk of overlooked precancerous polyps and subsequent risk of post-colonoscopy colorectal cancer (PCCRC). We investigated whether patients with T2D are at increased risk of PCCRC compared with patients without T2D. DESIGN: We conducted a population-based cohort study of patients with T2D and without T2D undergoing colonoscopy in Denmark (1995-2015). We investigated the risk of PCCRC by calculating >6 to 36 months cumulative incidence proportions (CIPs) treating death and colectomy as competing risks. Using Cox proportional-hazards regression analyses, we also computed HRs of PCCRC, comparing patients with T2D and non-T2D. According to the World Endoscopy Organization guidelines, we calculated PCCRC 3-year rates to estimate the proportions of T2D and non-T2D CRC patients experiencing PCCRC. RESULTS: We identified 29 031 patients with T2D and 333 232 patients without T2D undergoing colonoscopy. We observed 250 PCCRCs among patients with T2D and 1658 PCCRCs among patients without T2D. The >6 to 36 months CIP after a first-time colonoscopy was 0.64% (95% CI 0.55% to 0.74%) for T2D and 0.36% (95% CI 0.34% to 0.38%) for patients without T2D. The HRs of PCCRC were 1.43 (95% CI 1.21 to 1.72) after a first-time colonoscopy and 1.18 (95% CI 0.75 to 1.85) after a second-time colonoscopy. The PCCRC 3-year rate was 7.9% for patients with T2D and 7.4% for patients without T2D. CONCLUSION: T2D may be associated with an increased HR of PCCRC.

Venous Thromboembolism and Risk of Cancer in Patients with Diverticular Disease: A Danish Population-Based Cohort Study.

PURPOSE: 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 cancer in patients with diverticular disease.

Venous thromboembolism and risk of cancer in users of statins: A Danish population-based cohort study.

BACKGROUND: Venous thromboembolism (VTE) may be the first symptom of cancer. Statins are suggested to prevent VTE, but the risk of cancer in VTE patients using statins remains poorly understood. OBJECTIVES: To examine if VTE is a marker of cancer in users of statins. METHODS: We identified all Danish patients during 1996-2017 with a first-time diagnosis of VTE and a filled prescription for a statin within 90 days prior to the VTE diagnosis. We classified patients as prevalent users if the first filling of a statin occurred more than one year preceding the VTE diagnosis, and as new users if the first filling occurred within the preceding year. We computed cumulative incidences of cancer, with death as a competing risk, and age-, sex-, and calendar-period standardized incidence ratios (SIRs), comparing the observed cancer incidence with the expected based on national cancer statistics. RESULTS: Among 9280 (85%) prevalent users of statin and 1580 (15%) new users, the one-year cumulative incidence of any cancer was 6.6 (95% CI: 6.1-7.2) for prevalent users and 6.4 (95% CI: 5.2-7.6) for new users; the corresponding SIRs were 3.1 (95% CI: 2.9-3.3) and 3.5 (95% CI: 2.9-4.3). In the second and subsequent years, the SIRs diminished and approached unity for both prevalent (1.1 [95% CI: 1.1-1.2]) and new users (1.1 [95% CI: 0.9-1.3]). CONCLUSIONS: VTE patients using statins had a 3-fold increased rate of cancer in the first year after diagnosis. A first VTE serves as an important marker of cancer, regardless of statin use.

Risk of lower gastrointestinal bleeding and colorectal neoplasms following initiation of low-dose aspirin: a Danish population-based cohort study.

OBJECTIVE: Aspirin may increase the risk of lower gastrointestinal bleeding (LGIB) from precursors of colorectal cancer (CRC). We investigated whether use of low-dose aspirin, through initiation of LGIB, may lead patients to undergo colonoscopy and polypectomy before manifest CRC. DESIGN: We conducted a historical cohort study (2005-2013) of all Danish residents who initiated low-dose aspirin treatment (n=412 202) in a setting without screening for CRC. Each new aspirin user was matched with three non-users (n=1 236 560) by age, sex and region of residence on the date of their matched new user's first-time aspirin prescription (index date). We computed absolute risks (ARs), risk differences and relative risks (RRs) of LGIB, lower gastrointestinal endoscopy, colorectal polyps and CRC, comparing aspirin users with non-users. RESULTS: The ARs were higher for new users than non-users for LGIB, lower gastrointestinal endoscopy, colorectal polyps and CRC within 3 months after index. Comparing new users with non-users, the RRs were 2.79 (95% CI 2.40 to 3.24) for LGIB, 1.73 (95% CI 1.63 to 1.84) for lower gastrointestinal endoscopy, 1.56 (95% CI 1.42 to 1.72) for colorectal polyps and 1.73 (95% CI 1.51 to 1.98) for CRC. The RRs remained elevated for more than 12 months after the index date, with the exception of CRC where the RRs were slightly decreased during the 3-5 years (RR 0.90, 95% CI 0.83 to 0.98) and more than 5 years (RR 0.91, 95% CI 0.82 to 1.00) following the index date. CONCLUSION: These findings indicate that aspirin may contribute to reduce CRC risk by causing premalignant polyps to bleed, thereby expediting colonoscopy and polypectomy before CRC development.

Antibiotic Use in Childhood and Adolescence and Risk of Inflammatory Bowel Disease: A Case-Control Study in the UK Clinical Practice Research Datalink.

BACKGROUND: Inflammatory bowel disease (IBD) causes serious morbidity and disability, and the incidence is increasing. The disease etiology is not well understood, though inflammatory reactions after antibiotic exposure may be associated with development of IBD. We investigated the association between IBD and prior antibiotic use. METHODS: We conducted this case-control study among individuals in the United Kingdom Clinical Practice Research Datalink GOLD (CPRD GOLD). Each case of IBD was matched to 4 controls on age, sex, general practice, and registration year in the CPRD GOLD. Antibiotic exposure was classified by ever or never use, number of prescriptions, and class of antibiotic before the index date. Odds ratios were calculated using conditional logistic regression. RESULTS: We identified 461 cases of ulcerative colitis (UC) and 683 cases of Crohn's disease (CD). There was no association between ever use of any antibiotic and UC (odds ratio [OR], 1.02; 95% confidence interval [CI], 0.72-1.44) or CD (OR, 1.01; 95% CI, 0.73-1.39) compared with never use. A slightly increased CD risk was observed among ever users of quinolones (OR, 1.76; 95% CI, 1.00-3.11) and metronidazole (OR, 1.43; 95% CI, 0.87-2.34) compared with never users. CD was associated with antibiotic exposure before age 5 (OR, 2.20; 95% CI, 0.75-6.43) in an analysis restricted to individuals followed from birth. CONCLUSIONS: There was no association between UC or CD and overall prior use of antibiotics, though prior use of metronidazole and quinolones was associated with a slightly increased risk of CD. Antibiotic use in early childhood may increase the risk of CD.

[Fistula construction in a late anastomotic leakage].

Post-operative bowel perforation is often a consequence of an anastomotic leakage. In most cases of major anastomotic leakage with generalised peritonitis a stoma formation at the point of perforation is recommended. In some cases, however, stoma formation is not possible. In this case report an artificial fistula was made. The edge of the defect in the anastomosis was sutured to an incision in the iliac fossa to provide source control in a difficult case of anastomotic leakage. The abdominal cavity was found without faecal contamination on the fourth post-operative day.