Michael Due Larsen

The Impact of the Quality of Colon Preparation on Follow-Up Colonoscopy Recommendations

OBJECTIVES:Published guidelines for timing of follow-up colonoscopy assume that the entire colon mucosa is visualized and provide no guidance in the case of poor preparations. We aimed to determine how preparation quality during screening colonoscopy affects gastroenterologists’ recommendations on the timing of follow-up colonoscopy.METHODS:Gastroenterologists were shown representative images of four colonoscopies with differing colon-preparation quality. For each set of images they were asked to recommend when a hypothetical patient with no polyps or malignancy on screening examination should return for a subsequent colonoscopy. For the same patient, gastroenterologists were asked to give recommendations based on a preparation-quality grading scale.RESULTS:The survey was completed by 239 gastroenterologists. Nearly all recommended 10-year follow-up colonoscopy for the best-appearing preparation. For the three imperfect preparations there was considerable variability in recommendations; follow-up timing ranged from 1–2 days to 10 years for identical preparations. Similar variability was seen in recommendations based on a preparation-quality grading scale. Endoscopists generally recommended progressively shorter-interval follow-up as colon preparation worsened, with median recommended follow-up of 10, 5, 1, and 0.25 years for the four sets of images. No association was seen between personal demographics or practice characteristics and follow-up recommendations.CONCLUSIONS:When colon preparation is imperfect, gastroenterologists provide highly variable recommendations regarding timing of follow-up colonoscopy.

Dynamics of vitamin K antagonist and new oral anticoagulants use in atrial fibrillation: a Danish drug utilization study

Detailed data on real‐life utilization of vitamin K antagonists (VKAs) and new oral anticoagulants (NOACs) in atrial fibrillation are sparse.

A MiniReview of the Use of Hospital-based Databases in Observational Inpatient Studies of Drugs

The majority of pharmacoepidemiological data resources are based on data generated in primary health care. Although inpatient data resources have existed since the 1960s, inpatient pharmacoepidemiological studies are relatively scarce. The objectives of this MiniReview were to describe pharmacoepidemiological studies in hospital settings and the underlying databases to provide an overview of research questions addressed by such databases. The studies were retrieved by chain searching. We included pharmacoepidemiological studies in hospital settings containing data on inpatient drug use. Twelve inpatient databases in Asia, the United States and Europe were found. Most databases were automatically collected from claims data or generated from electronic medical records. The contents of the databases varied as well as the potential for linkage with other data sources such as laboratory and outpatient data. Twenty studies were selected and discussed to illustrate the diversity of inpatient pharmacoepidemiological studies. Hospital-based databases had mainly been used for drug utilization studies and research in adverse drug reactions. Five studies within comparative effectiveness were found. The number of pharmacoepidemiological studies in inpatient settings was low compared with studies from primary healthcare settings. These resources may be under-utilized.

Reassuring results on birth outcomes in children fathered by men treated with azathioprine/6-mercaptopurine within 3 months before conception: a nationwide cohort study

Objective Information on the safety of paternal use of azathioprine (AZA) and 6-mercaptopurine (6-MP) prior to conception is limited. Based on nationwide data from the Danish health registries, we examined the association between paternal use of AZA/6-MP within 3 months before conception and adverse birth outcomes. Design This nationwide cohort study is based on data from all singletons born in Denmark from 1 January 1997 through 2013. Children fathered by men who used AZA/6-MP within 3 months before conception constituted the exposed cohort (N=699), and children fathered by men who did not use AZA/6-MP 3 months prior to conception constituted the unexposed cohort (N=1 012 624). The outcomes were congenital abnormalities (CAs), preterm birth and small for gestational age (SGA). We adjusted for multiple covariates and performed a restricted analysis of men with IBD. Results There were no significantly increased risks of CAs, preterm birth or SGA in exposed versus unexposed cohorts of children. The adjusted ORs were 0.82 (95% CI 0.53 to 1.28) for CAs, 1.17 (95% CI 0.72 to 1.92) for preterm birth and 1.38 (95% CI 0.76 to 2.51) for SGA. Restricting our analysis to fathers with IBD showed similar results with no significantly increased risk of adverse birth outcomes. Conclusions This nationwide study is the largest to date, examining the effect of preconceptual paternal use of AZA/6-MP on birth outcomes in live born singletons. The results of no significantly increased risks of adverse birth outcomes are reassuring and support the continuation of paternal AZA/6-MP treatment during conception.

Live birth and adverse birth outcomes in women with ulcerative colitis and Crohn's disease receiving assisted reproduction: a 20-year nationwide cohort study

Objective To examine the chance of live births and adverse birth outcomes in women with ulcerative colitis (UC) and Crohns disease (CD) compared with women without inflammatory bowel disease (IBD) who have undergone assisted reproductive technology (ART) treatments. Methods This was a nationwide cohort study based on Danish health registries, comprising all women with an embryo transfer during 1 January 1994 through 2013. The cohorts comprised 1360 ART treatments in 432 women with UC, 554 ART treatments in 182 women with CD and 148 540 treatments in 52 489 women without IBD. Our primary outcome was live births per ART treatment cycle. We controlled for multiple covariates in the analyses. Our secondary outcomes were adverse birth outcomes. Results The chance of a live birth for each embryo transfer was significantly reduced in ART treatments in women with UC (OR=0.73, 95% CI 0.58 to 0.92), but not significantly reduced in the full model of ART treatments in women with CD (OR=0.77, 95% CI 0.52 to 1.14). Surgery for CD before ART treatment significantly reduced the chance of live birth for each embryo transfer (OR=0.51, 95% CI 0.29 to 0.91). In children conceived through ART treatment by women with UC, the OR of preterm birth was 5.29 (95% CI 2.41 to 11.63) in analyses including singletons and multiple births; restricted to singletons the OR was 1.80, 95% CI 0.49 to 6.62. Conclusions Our results suggest that women with UC and CD receiving ART treatments cannot expect the same success for each embryo transfer as other infertile women. Women with CD may seek to initiate ART treatment before needing CD surgery. Increased prenatal observation in UC pregnancies after ART should be considered.

Birth Outcomes in Children Fathered by Men Treated with Anti-TNF-α Agents Before Conception.

Objectives:The safety of paternal use of anti-tumor necrosis factor-α (TNF-α) agents immediately prior to conception is practically unknown. On the basis of nationwide data from Danish health registries, we examined the association between paternal use of anti-TNF-α agents within 3 months before conception and adverse birth outcomes.Methods:This nationwide cohort study is based on data from all women who had a live born singleton child in Denmark from 1 January 2007 through 2013. Children fathered by men treated with anti-TNF-α agents within three months before conception constituted the exposed cohort (N=372), and children fathered by men not treated before conception constituted the unexposed cohort (N=399,498). The outcomes were congenital abnormalities (CAs), preterm birth, and small for gestational age (SGA). We adjusted for multiple covariates, and considered paternal underlying disease and concomitant medication.Results:The adjusted risks of CAs and preterm birth were close to unity, and the adjusted odds ratio (OR) for SGA was 1.70 (95% confidence interval (CI): 0.94–3.09). Restricting our analysis to fathers with inflammatory bowel disease, we found no increased risk of CAs or SGA, and the adjusted OR for pretem birth was 1.42 (95% CI: 0.52–3.86). Restricting our analysis to fathers with rheumatologic/dermatological diseases, we found no increased risk of CAs or preterm birth, and the adjusted OR for SGA was 1.70 (95% CI: 0.74–3.89).Conclusions:Our results are overall reassuring regarding the safety of paternal preconceptional use of anti-TNF-α agents. The result regarding SGA should, however, be interpreted with caution as we found an increased risk, although not significantly increased.

Use of Anti-TNFα Agents and Time to First-time Surgery in Paediatric Patients with Ulcerative Colitis and Crohn’s Disease

BACKGROUND AND AIMS It is debated whether the need for surgery has changed following introduction of anti-TNFα agents in the treatment of paediatric ulcerative colitis [UC] and Crohns disease [CD]. We aimed to describe the implementation of anti-TNFα agents in paediatric patients, and the need of first-time surgery before and after introduction of anti-TNFα agents. METHODS In the Danish National Patient Registry, we identified incident paediatric patients diagnosed from 1998. We calculated the proportion of patients receiving anti-TNFα agents within 5 years from diagnosis, and the cumulative 5 year proportion of surgery, according to calendar periods of diagnosis. RESULTS At the end of our study period [2007 and 2008], 29-41% of CD children were treated with anti-TNFα agents within 5 years, and for UC children 17-19%. In 1278 CD patients, the 5 year cumulative proportions of surgery were 14.6-15.6% for children diagnosed in 1998-2008 and 9.7% (95% confidence interval [CI]: 6.7-13.7) for those diagnosed in 2009-2013. In 1468 UC patients, the cumulative proportion of surgery suggested a decline in patients diagnosed after mid 2005, and the hazard ratio of surgery was 0.64 [95% CI: 0.47-0.86] after the introduction of anti-TNFα agents compared with before. For UC patients diagnosed in 2009-2013, the 5 year cumulative proportion of surgery was 7.6% [95% CI: 5.2-11.2]. CONCLUSIONS This nationwide study showed an extensive use of anti-TNFα agents at the end of our study period. For UC children, our data suggest a decline in the proportion of surgery in the period of increasing use of anti-TNFα agents.

The incidence of Crohn’s disease and ulcerative colitis since 1995 in Danish children and adolescents <17 years – based on nationwide registry data

Abstract Objective: Worldwide the incidence of pediatric Crohn’s disease (CD) and ulcerative colitis (UC) is suspected to be increasing. Based on unselected nationwide register data the aim of this study is to examine the change in incidence of CD and UC in children and adolescents in Denmark. Materials and methods: All children and adolescents <17 years with a diagnosis of CD or UC registered in the Danish National Patient Registry from 1 January 1995 to 31 December 2013 were included. Using a Poisson regression model we estimated the incidence rate ratio (IRR) for the annual change in the incidence adjusted for gender and age. The cumulative incidence was described using Kaplan–Meier survival analyses. Results: The IRR for CD was 1.052 (95% CI: 1.039–1.065), and for UC the IRR was 1.022 (95% CI: 1.011–1.033), adjusted for age and gender. The incidence rate of CD increased during the study period to 10.0 (95% CI: 7.5–13.2) per 100,000 person years for girls and 9.4 (95% CI: 7.0–13.2) for boys, in 2013. Similar, the incidence of UC increased to 7.2 (95% CI: 5.0–9.9) per 100,000 person years for girls and 6.2 (95% CI: 4.3–8.7) for boys. Conclusions: In a period of 19 years from 1995 to 2013 we found an increasing incidence for pediatric UC and CD, especially pronounced for CD.

Paternal use of azathioprine/6-mercaptopurine or methotrexate within 3 months before conception and long-term health outcomes in the offspring—A nationwide cohort study

PURPOSE We examined the effect of preconception paternal use of azathioprine (AZA)/6-mercaptopurine (6-MP) or methotrexate (MTX) and the risk of adverse long-term outcomes in the offspring. METHODS This study included all children born in Denmark from 1 January 1997 through 2013. Exposed cohort: children fathered by men who used AZA/6-MP (N=735) or MTX (N=209) within three months before conception; unexposed cohort: children fathered by men who did not use AZA/6-MP/MTX (N=1,056,524). OUTCOMES malignancies, autism spectrum disorders (ASD)/schizophrenia/psychosis, and attention deficit hyperactivity disorder (ADHD). RESULTS Outcomes: of children: AZA/6-MP exposure: one with leukemia (0.14%), one with ASD/schizophrenia (0.14%) and three with ADHD (0.41%); MTX exposure: three with ADHD (1.4%). Unexposed: 1710 with malignancies (0.16%), 2107 with ASD/schizophrenia (0.20%), 2799 with ADHD (0.26%). Median follow up times were 6.7 [IQR:3.6-11.3] and 9.9 [IQR:5.7-14.3] years respectively. CONCLUSIONS There was no negative impact of paternal preconception use of AZA/6-MP/MTX on selected childhood health outcomes.

Danish Urogynaecological Database

The Danish Urogynaecological Database is established in order to ensure high quality of treatment for patients undergoing urogynecological surgery. The database contains details of all women in Denmark undergoing incontinence surgery or pelvic organ prolapse surgery amounting to ~5,200 procedures per year. The variables are collected along the course of treatment of the patient from the referral to a postoperative control. Main variables are prior obstetrical and gynecological history, symptoms, symptom-related quality of life, objective urogynecological findings, type of operation, complications if relevant, implants used if relevant, 3–6-month postoperative recording of symptoms, if any. A set of clinical quality indicators is being maintained by the steering committee for the database and is published in an annual report which also contains extensive descriptive statistics. The database has a completeness of over 90% of all urogynecological surgeries performed in Denmark. Some of the main variables have been validated using medical records as gold standard. The positive predictive value was above 90%. The data are used as a quality monitoring tool by the hospitals and in a number of scientific studies of specific urogynecological topics, broader epidemiological topics, and the use of patient reported outcome measures.