Paracetamol overdose in Danish children and adolescents during the Covid-19 restrictions.

INTRODUCTION: To assess the effect of long-term isolation on the mental state of Danish youth. This study aimed to investigate trends in paracetamol overdoses among people under 18 years of age in Denmark during Covid-19 restrictions as an indicator of mental health. METHODS: All patients under the age of 18 years presenting with paracetamol overdose at one of the 18 paediatric departments in Denmark from 2016 to 2021 were included. They were identified in all Danish hospital databases using specific diagnostic codes. RESULTS: From 2016 to 2021, a total of 3,217 people under 18 years of age were admitted for paracetamol overdose. Among these, 86% (n = 2,755) were girls and 14% (n = 462) were boys. During 2020, a slight (7%) decrease in admissions was observed among both boys and girls compared with the preceding four-year mean value. In 2021, the number of overdoses among girls exceeded by 35% the former all-time high from 2016. Furthermore, the number of overdoses among girls exceeded the pre-four-year period mean value by 43%. Among boys, an 8% increase was seen from the highest ever previous value recorded in 2019 and a 23% increase compared with the previous four-year mean value. CONCLUSIONS: During the first year of restrictions, a slight decrease in paracetamol overdoses was observed, possibly associated with limited accessibility. The second year showed a considerable increase in paracetamol overdoses, which may imply an affected mental state among youth during the prolonged lockdown restrictions as seen in previous epidemics. Therefore, further studies are warranted to develop a pandemic preparedness plan to protect general mental health. FUNDING: None. TRIAL REGISTRATION: Not relevant.

Children and Adolescents Diagnosed With Inflammatory Bowel Disease Are at Increased Risk of Developing Diseases With a Possible Autoimmune Pathogenesis.

BACKGROUND: The development of diseases with a possible autoimmune pathogenesis is common in adults with inflammatory bowel disease (IBD). In early onset IBD, it may differ but the evidence is sparse. We aimed to investigate the risk and time span from IBD diagnosis to outcomes with different associated disorders with possible autoimmune pathogenesis. METHODS: A register-based study included all Danish patients with early onset of IBD (≤18 years) between 1980 and 2021 and 50 matched references without IBD for each case. We examined the risk of type 1 and type 2 diabetes, celiac disease, thyroid disease, rheumatoid arthritis, psoriatic arthritis, and spondyloarthritis in Cox regression models. RESULTS: In total, 6822 patients with IBD were identified, and 337 728 matched references. The median age at the time of IBD diagnosis or index date for the matched references was 16 years (25-75 percentile: 13-18 years), and the median age at the time of an outcome or at the end of follow-up was 28.1 years (25-75 percentile: 21.5-37.0 years). According to the cumulative incidence plots psoriatic arthritis, and spondyloarthritis was diagnosed approximately 10 years after the IBD onset, and the remaining outcomes later. The adjusted hazard ratio after full follow-up was 4.72 (95% CI, 3.85-5.80) for psoriatic arthritis, 5.21 (95% CI, 4.17-6.50) for spondyloarthritis, 2.77 (95% CI, 1.92-4.00) for celiac disease, 2.15 (95% CI, 1.54-3.01) for rheumatoid arthritis, 1.69 (95% CI, 1.23-2.32) and 1.64 (95% CI, 1.21-2.21) for type 1 and type 2 diabetes, respectively. For thyroid disease, it was 1.16 (95% CI, 0.97-1.40). CONCLUSIONS: The risk estimates were significantly increased for all outcomes at the end of follow-up, except for thyroid disease, but according to the cumulative incidence plots, only psoriatic arthritis and spondyloarthritis occurred earlier in the IBD cohort than in the matched references.

Children and adolescents diagnosed with inflammatory bowel disease are at increased risk of developing several diseases with possible autoimmune pathogenesis compared with a matched reference group. Cumulative incidence curves showed that psoriatic arthritis and spondyloarthritis debut in young adulthood when compared with a matched reference group without IBD.

Implication of Inflammatory Bowel Disease Diagnosed Before the Age of 18 for Achieving an Upper Secondary Education: A Nationwide Population-Based Cohort Study.

BACKGROUND: Educational achievement may be adversely affected by chronic conditions in childhood and adolescence. This study aimed to examine the effect of being diagnosed with IBD on achievement of an upper secondary education and the influence of disease severity and psychiatric comorbidity. METHODS: This cohort study was based on nationwide Danish administrative registries. We compared a cohort of patients with IBD with a matched population-based cohort. The IBD cohort included patients born between 1970 and 1994 who were diagnosed with IBD (age <18 years). The outcome was achieving an upper secondary education and was analyzed using Cox regression. The impact of disease severity (expressed by surgery or corticosteroid prescriptions) or psychiatric comorbidity within the IBD cohort was assessed using Poisson regression. RESULTS: We identified 3178 patients with IBD (Crohn's disease [CD] n = 1344, ulcerative colitis [UC] n = 1834) and matched them with 28 204 references. The hazard ratio of achieving an upper secondary education was 1.14 (95% confidence interval, 1.07-1.21) for CD and 1.16 (95% confidence interval, 1.10-1.23) for UC. In the IBD cohort, having surgery, a steroid prescription, or a comorbid psychiatric condition was associated with a lower chance of achieving an upper secondary education. CONCLUSION: Being diagnosed with IBD before 18 years of age increased the chance of achieving an upper secondary education. However, patients with more severe disease or psychiatric comorbidity were at higher risk of not achieving an upper secondary education than patients with milder disease.

The IBD-FITT study - moderate-intensity exercise for patients with inflammatory bowel disease with moderate disease activity: an open-label randomized controlled trial.

BACKGROUND: Inflammatory bowel disease (IBD), Crohn's disease, and ulcerative colitis are chronic autoimmune lifelong diseases with fluctuating activity over time. The treatment includes medical therapy and surgery, however, there is no definite cure. Therefore, the quest for new and supplementary treatment options is imperative to improve patients' general health and quality of life. Physical activity and exercise have been suggested to be elements in both the prevention and supplementary treatment of IBD; however, this is based on limited underpowered trials. Thus, the role of exercise as a treatment option still has to be settled. We aim to investigate the effect of a 12-week exercise intervention in adult patients with moderately active IBD on three categories of outcomes (1) disease-specific health-related quality of life (IBDQ); (2) general health status of the patients, i.e., waist circumference, disease activity by clinical scorings systems (Harvey Bradshaw Index, Simple Clinical Colitis Activity Index), blood pressure, blood lipids, and non-disease specific quality of life (EQ5D) scores; and (3) explorative outcomes on biomarkers (C-reactive protein and fecal calprotectin) plus different biomarkers of immunology (cytokine panel). METHODS: We will apply a superiority design in this open-label randomized clinical trial including 150 patients equally allocated to intervention and usual care. The intervention will be based on a 12-week aerobic exercise program and will include two supervised exercise sessions of 60 min per week, combined with one weekly home training session. We have defined a moderate exercise level as 60-80% of patients' maximum heart rate. The patients in the intervention group will also be offered an online video lesson of 15-25 min on lifestyle guidance, and the same online video lesson will be offered in the comparator group. Questionnaires on quality of life will be forwarded electronically both at inclusion and at the end of the study, and the patients will have blood samples, and fecal samples for calprotectin at baseline, weeks 4 and 8, as well as after 12 weeks (study end). DISCUSSION: This will be a clinical trial investigating the effect of exercise on patients with Crohn's disease and ulcerative colitis. This trial will add to the evidence on the possible effect of exercise and might clarify whether exercise can benefit as a supplementary treatment addendum. Thus, the trial may provide a new patient-active disease management approach. TRIAL REGISTRATION: ClinicalTrials.gov NCT04816812. Date of first registration: March 23, 2021.

A population-based nationwide study on total colectomy for ulcerative colitis and risk of ten prevalent inflammatory or autoimmune diseases.

BACKGROUND: There is growing evidence to support a role of the gut microbiome in the development of chronic inflammatory and autoimmune disease (IAD). We used total colectomy (TC) for ulcerative colitis (UC) as a model for a significant disruption in gut microbiome to explore an association with subsequent risk of IAD. METHODS: We identified all patients with UC and no diagnosis of IAD prior to their UC diagnosis in Denmark from 1988 to 2015. Patients were followed from the date of UC to a diagnosis of IAD, death or end of follow-up, whichever occurred first. We used Cox regression to estimate hazard ratios (HRs) of IAD associated with TC, adjusting for age, sex, Charlson Comorbidity Index, and calendar year of UC diagnosis. RESULTS: 30,507 patients with UC (3,155 with TC and 27,352 without) were identified from the Danish National Patient Registry. During 43,266 person-years of follow-up, 2733 patients were diagnosed with an IAD. The risk of any IAD was higher for patients with TC compared to patients without (adjusted HR [aHR] 1.39 (95% CI: 1.24-1.57)). When the analyses were adjusted for exposure to antibiotics, immunomodulatory medicine and biologics (covering 2005-2018), the risk of IAD was still higher for patients with total colectomy (aHR = 1.41 (95% CI: 1.09;1.83)). Disease-specific analyses were weakened by a low number of outcomes. CONCLUSIONS: The risk of IAD was higher for patients who underwent TC for UC compared to patients who did not.KEY MESSAGESWhat is already known?o The gut microbiome plays an important role in host immune homeostasis, and changes in gut bacterial diversity and composition may change the individual's risk of inflammatory and autoimmune disease (IAD).What is new here?o Patients with ulcerative colitis who undergo total colectomy have a higher risk of being diagnosed with IAD, compared to patients with ulcerative colitis who do not undergo total colectomy.How can this study help patient care?o Future research can help uncover the mechanisms responsible for the higher risk of certain IADs after total colectomy. If the microbiome plays a role, modifying the gut microbiome could prove a viable therapeutic strategy to reduce the risk of developing IADs.

In this nationwide Danish cohort study of all Danish UC patients diagnosed in the period from 1988 to 2015, the risk of being diagnosed with inflammatory and autoimmune disease is higher for patients who underwent total colectomy compared to UC patients without total colectomy.

Health-Related Quality of Life, Anxiety, and Self-Image in Young Patients With Crohn's Disease and Ulcerative Colitis.

We examined health-related quality of life, anxiety, and self-image in patients aged 10-20 years with Crohn's disease (CD) and ulcerative colitis (UC) in remission. These areas are key concerns in clinical care. We used the IMPACT-III for health-related quality of life and The Beck Youth Inventory-II for anxiety and self-image. Linear regression models were used to compare CD to UC. We included 67 patients, 44 (66%) with CD and 23 (34%) with UC. The mean score for IMPACT-III, anxiety, and self-image for CD versus UC was 78 (±SD: 13) versus 78 (±SD: 15), 44 (±SD: 9) versus 45 (±SD: 8), and 10 (±SD: 9) versus 9 (±SD: 6), respectively. We found no difference between CD and UC. Despite remission, we found an elevated score of anxiety and a low score of self-image. When evaluating mental health status, a varied approach may be beneficial for researchers.

Use of proton pump inhibitors in scandinavian children and adolescents: An observational study.

Aims: To examine the use of proton pump inhibitors (PPIs) in Scandinavian children with focus on the geographical variation, temporal changes and possible contributing factors to observed changes. Methods: An observational population-based study of children and adolescents (1-17 years) in Norway, Sweden, and Denmark during the period 2007-2020. Information concerning dispensed PPIs was obtained from the national prescription databases of each country and presented as means per 1,000 children for each country and calendar year in four age categories (1-4, 5-9, 10-13 and 14-17 years). Results: In 2007, the PPI use in children was similar across Scandinavian countries. An increased PPI use was observed in all countries during the study period, with gradually increasing differences between the countries. In general, Norway showed both the largest total increase and the largest increase in each age category compared to Sweden and Denmark. In 2020 Norwegian children showed, on average, a 59% higher PPI use compared to Swedish children and a more than double the overall dispensation rate than Denmark. In Denmark there was a 19% reduction in dispensed PPIs from 2015 to 2020. Conclusion: Despite being countries with similar health care systems and without indications of increased incidence of gastroesophageal reflux disease (GERD), we observed considerable geographical variation and temporal changes of PPI use in children. Although this study did not contain data on the indication for PPI use, these large differences across countries and time may indicate a current overtreatment.

Disease Status at Diagnosis in Danish Children with α 1 -antitrypsin Deficiency.

OBJECTIVES: The aim of this cross-sectional study was to assess the state of disease at the time of diagnosis in Danish children with α 1 -antitrypsin deficiency as Denmark has a high prevalence of ZZ-homozygosity. METHODS: Children either heterozygous, compound heterozygous, or homozygous for Z- and S-variants in the SERPINA1 -gene were included. Clinical characteristics, SERPINA1 -genotype, and blood serum (S) concentrations were recorded concurrently with genetic testing. Serum liver marker concentrations were compared using T tests and Wilcoxon-Mann-Whitney tests. Generalized estimating equation (GEE) linear regression models, both univariable and multivariable adjusted for age and sex, were applied to identify correlations with serum α 1 -antitrypsin (S-AAT). The relationship between S-AAT concentration and genotype was assessed using logistic regression with GEE. RESULTS: The study included 183 of 225 children genetically tested for alpha-1-antitrypsin deficiency (AATD). Of these, 36.6% were homozygous for the Z-variant. Of the heterozygotes, 89.7% had a ZM genotype and the remaining had either an MS genotype or were compound heterozygous. At diagnosis, ZZ-homozygous children had higher serum concentrations of liver enzymes and conjugated bilirubin, but lower concentrations of S-AAT compared with heterozygotes. Serum concentrations of conjugated bilirubin and liver enzymes were negatively associated with S-AAT. Children under 6 months of age had higher total S-bilirubin concentrations than children over 6 months of age. CONCLUSIONS: A low S-AAT concentration is a strong indicator of homozygosity, and homozygous children have higher enzymatic and cholestatic parameters compared with heterozygous children at diagnosis. This underlines the importance of measuring the S-AAT concentration in children with prolonged neonatal jaundice.

Proton pump inhibitors for infants in three Scandinavian countries increased from 2007 to 2020 despite international recommendations.

AIM: There is weak evidence that proton pump inhibitors (PPIs) alleviate non-specific complaints often attributed to gastroesophageal reflux in infancy and international guidelines do not recommend their use. We studied PPIs dispensed for infants in three Nordic countries. METHODS: This was an observational population-based study of infants living in Norway, Sweden and Denmark in 2007-2020. We used nationwide pharmaceutical registers to study dispensed PPIs. The data provided a total of 3.3 million observed years on about 240 000 annual births. RESULTS: The overall use of PPIs in infancy showed a marked increase in all three countries from 2007 to 2020. In 2020, PPI dispensing was 46.4, 23.4 and 18.9 per 1000 per year in infants aged 0-11 months in Denmark, Norway and Sweden. These were increases of 357%, 585% and 556% respectively. Although the rate was highest in Denmark, it had decreased by 42% in the last 3 years of the study. CONCLUSION: Despite international recommendations against routine PPI prescribing in infancy, dispensed PPIs increased more than fourfold on average in three Nordic countries from 2007 to 2020. The reason for this notable increase could not be established from the data, but the large variations over time, and between the countries, probably indicated unwarranted use.

Physical activity measured by accelerometry in paediatric and young adult patients with inflammatory bowel disease.

OBJECTIVES: Physical activity in paediatric and young adult patients suffering from inflammatory bowel disease (IBD) may play an important role in the overall health status. However, physical activity in these patients has not been reported using objective methods. We aimed to describe accelerometry-measured physical activity levels in paediatric and young adult IBD patients with either ulcerative colitis (UC) or Crohn's disease (CD). METHODS: We recruited Danish patients with IBD aged 10-20 years in clinical remission and with a faecal calprotectin below 200 µg/mg. Physical activity was assessed using tri-axial wrist accelerometry over seven days and quantified using the activity-related acceleration derived as the conventional Euclidian Norm Minus One (ENMO) metric expressed in milli-gravity units (mg). Time spent in Moderate-to-Vigorous Physical Activity (MVPA) was classified as ENMO > 210 mg in 5 s epoch resolution (unbouted). RESULTS: We included 61 patients with a median age of 17 years [Inter Quartile Range, IQR 14-19]. The total volume of activity expressed as average acceleration (ENMO) per day was 31.5 mg (95% CI 29.1-33.9). Time spent in unbouted MVPA was 32 min per day (95% CI 26-37). There was no significant difference in activity volume between patients with UC to patients with CD, the adjusted linear regression coefficient was - 1.7 mg (95% CI -6.2-2.7). Activity volume was higher for males (36.2 mg, 95% CI 31.9-40.5) than for females (27.8 mg, 95% CI 25.6-30.0), and younger patients were more active than older patients; Activity volume in 10-13 year olds was 37.2 mg (95% CI 28.6-45.7), whereas it was 28.5 mg (95% CI 25.2-31.7) for those aged 18-20 years. CONCLUSIONS: We collected tri-axial accelerometry in young patients with IBD in clinical remission, and described their level of physical activity by the conventional ENMO measure. We found no statistically significant difference in patients with UC compared to patients with CD. The volume of physical activity was higher in males compared to females, and inversely associated with age.

Outcome of COVID-19 in hospitalized patients with chronic inflammatory diseases. A population based national register study in Denmark.

OBJECTIVE: COVID-19 has substantial morbidity and mortality. We studied whether hospitalized patients with COVID-19 and chronic inflammatory diseases experienced worse outcomes compared to patients hospitalized with COVID-19 without chronic inflammatory diseases. METHODS: Danish nationwide registers were used to establish a cohort of hospitalized patients with COVID-19 and inflammatory bowel diseases (IBD), rheumatoid arthritis (RA), spondyloarthropathy (SpA), or psoriatic arthritis (PsA) (exposed), and a control cohort without these diseases (unexposed) between March 1, 2020, and October 31, 2020. We compared median length of hospital stay, used median regression models to estimate crude and adjusted differences. When estimating crude and adjusted odds ratio (OR) for continuous positive airway pressure (CPAP) and mechanical ventilation, in-hospital death, 14-day and 30-day mortality, we used logistic regression models. RESULTS: We identified 132 patients with COVID-19 and IBD, RA, SpA, or PsA, and 2811 unexposed admitted to hospital with COVID-19. There were no differences between exposed and unexposed regarding length of hospital stay (6.8 days vs. 5.5 days), need for mechanical ventilation (7.6% vs. 9.4%), or CPAP (11.4% vs. 8.8%). Adjusted OR for in-hospital death was 0.71 (95% CI 0.42-1.22), death after 14-days 0.70 (95% CI 0.42-1.16), and death after 30-days 0.68 (95% CI 0.41-1.13). CONCLUSION: Hospitalized patients with COVID-19 and chronic inflammatory diseases did not have statistically significant increased length of hospital stay, had same need for mechanical ventilation, and CPAP. Mortality was similar in hospitalized patients with COVID-19 and chronic inflammatory diseases, compared to patients hospitalized with COVID-19 and no chronic inflammatory diseases.

Infliximab, Immunomodulators and Treatment Failures in Paediatric and Adolescent Patients with Crohn's Disease: a Nationwide Cohort Study.

BACKGROUND AND AIMS: In paediatric patients with Crohn's disease, the role of combination therapy, infliximab plus immunomodulators [thiopurine or methotrexate], is debated and data are sparse. We examined whether infliximab plus immunomodulators, compared to infliximab therapy alone, reduces the risk of treatment failure measured by intestinal surgery or switching type of anti-tumour necrosis factor [TNF] α agent within 24 months. DESIGN: Using Danish registries, we identified patients with Crohn's disease, aged ≤ 20 years at the time of the first infliximab treatment, and retrieved data on their co-medications. We used Cox regression models to examine surgery or switching type of anti-TNFα agent from January 1, 2003 to December 31, 2015. RESULTS: We included 581 patients. The 2-year cumulative percentage of surgery was 8.5% among patients receiving combination therapy and 14.5% in those receiving infliximab alone. The adjusted 2-year hazard ratio [HR] of surgeries was 0.53 (95% confidence interval [CI] 0.32-0.88) in patients receiving combination therapy, compared to patients receiving infliximab alone. When examining a switch of anti-TNFα we included 536 patients. Within 2 years, 18.3% experienced a switch among patients receiving combination therapy and 24.8% in patients treated with infliximab alone, corresponding to an adjusted HR of 0.66 [95% CI 0.45-0.97] in patients receiving combination therapy. CONCLUSIONS: The HR of intestinal surgeries and the risk of a switch to another anti-TNFα was reduced in paediatric and adolescent patients receiving combination therapy, compared to patients receiving only infliximab. These results suggest a benefit for infliximab therapy combined with immunomodulators, but these need to be confirmed in data with additional clinical information.

Hospitalization for COVID-19 in patients treated with selected immunosuppressant and immunomodulating agents, compared to the general population: A Danish cohort study.

AIMS: In the Danish population, we examined whether patients treated with thiopurines, methotrexate, systemic corticosteroids, anti-tumour necrosis factor (TNF)-α agents, anti-interleukin therapeutic agents, selective immunosuppressive agents and cyclosporine/tacrolimus had an increased risk of hospitalization for COVID- 19, compared to the background population. METHODS: A nationwide cohort study including all people alive in Denmark on 1 March 2020. Exposed patients constituted those exposed to thiopurines (n = 5484), methotrexate (n = 17 977), systemic corticosteroids (n = 55 868), anti-TNF-α agents (n = 17 857), anti-interleukin therapeutic agents (n = 3744), selective immunosuppressive agents (n = 3026) and cyclosporine/tacrolimus (n = 1143) in a period of 12 months prior to 1 March 2020 (estimated time of outbreak in Denmark). We estimated the adjusted risk of hospitalization for COVID-19 for patients treated with the above-mentioned categories of medications, compared to the rest of the population. RESULTS: The adjusted odds ratios of hospitalization in patients treated with corticosteroids and cyclosporine/tacrolimus were 1.64 (95% confidence interval [CI] 1.35 to 2.00) and 4.75 (95% CI 1.96 to 11.49), respectively. The risks of hospitalization in patients treated with thiopurines, methotrexate, and anti-TNF-α agents, were 1.93 (95% CI 0.91 to 4.08), 0.74 (95% CI 0.43 to 1.28), 1.00 (95% CI 0.52 to 1.94), respectively. The number of outcomes in patients treated with anti-interleukin therapeutic agents and selective immunosuppressive agents was too small for analysis. CONCLUSION: Patients treated with systemic corticosteroids and cyclosporine/tacrolimus had a significantly increased risk of being hospitalized for COVID-19. Our study does not uncover whether the increased risk is related to the drug itself, the underlying condition for which the patient is treated or other factors.

Chronic diseases in the children of women with maternal thyroid dysfunction: a nationwide cohort study.

OBJECTIVE: Maternal thyroid disease (TD) during pregnancy is associated with adverse birth outcomes, but little is known on its long-term outcomes. We aimed to examine if children born to mothers with TD have increased disease risk during childhood and adolescence. PATIENTS AND METHODS: A register-based cohort study was conducted on all live born children in Denmark from 1989 to 2013, including the association between maternal TD during pregnancy and somatic and psychiatric diseases in the children. Cox proportional hazards models were used to compute hazard ratios (HRs) according to the type of maternal TD, Graves' disease, and Hashimoto's thyroiditis. RESULTS: A total of 2,618 children were born to women with Graves' disease, 760 to women with Hashimoto's thyroiditis (exposed), and 1,557,577 to women without any TD (unexposed). The median follow-up time for children born to mothers with Graves' disease was 9.3 years (25/75 percentile 5.4/13.9 years) and with Hashimoto's thyroiditis was 4.8 years (25/75 percentile 2.5/8.2 years). In children exposed to maternal Graves' disease in utero, the adjusted HR of TD was 12.83 (95% CI, 9.74-16.90), Graves' disease was 34.3 (95% CI, 20.23-58.35), and type 1 was diabetes 2.47 (95% CI, 1.46-4.18). In children exposed to maternal Hashimoto's thyroiditis, the adjusted HR of Hashimoto's thyroiditis was 24.04 (95% CI, 5.89-97.94). CONCLUSION: Our data suggest that children born to women with Graves' disease and Hashimoto's thyroiditis have excess long-term morbidities in childhood and adolescence. We particularly found an increased risk of any TD and type 1 diabetes to be diagnosed in children exposed in utero to Graves' disease. These novel findings are relevant for pediatricians, stressing the importance of history of maternal disease when evaluating children with suspected endocrine disorders.

Pediatric Inflammatory Bowel Diseases: Should We Be Looking for Kidney Abnormalities?

Background: Kidney disease has been reported in adults with inflammatory bowel disease (IBD) and is regarded an extraintestinal manifestation or more rarely a side effect of the medical treatment. Methods: In this cross-sectional study we describe the extent of kidney pathology in a cohort of 56 children with IBD. Blood and urine samples were analyzed for markers of kidney disease and ultrasonography was performed to evaluate pole-to-pole kidney length. Results: We found that 25% of the patients had either previously reported kidney disease or ultrasonographic signs of chronic kidney disease. The median kidney size compared with normal children was significantly reduced. In a multivariate linear mixed model, small kidneys significantly correlated with the use of infliximab, whereas the use of enteral nutritional therapy was associated with larger kidneys. Conclusion: Children with IBD are at risk of chronic kidney disease, and the risk seems to be increased with the severity of the disease.

The Danish National Registry for Biological Therapy in Inflammatory Bowel Disease.

AIM: The aims of The Danish National Registry for Biological Therapy in Inflammatory Bowel Disease are to ensure that biological therapy and the clinical management of patients with inflammatory bowel disease (IBD) receiving biological treatment are in accordance with the national clinical guidelines and, second, the database allows register-based clinical epidemiological research. STUDY POPULATION: The study population comprises all Danish patients with IBD (both children and adults) with ulcerative colitis, Crohn's disease, and IBD unclassified who receive biological therapy. Patients will be enrolled consecutively when biological treatment is initiated. MAIN VARIABLES: The variables in the database are: diagnosis, time of diagnosis, disease manifestation, indication for biological therapy, previous biological and nonbiological therapy, date of visit, clinical indices, physician's global assessment, pregnancy and breastfeeding (women), height (children), weight, dosage (current biological agent), adverse events, surgery, endoscopic procedures, and radiology. DESCRIPTIVE DATA: Eleven clinical indicators have been selected to monitor the quality of biological treatment. For each indicator, a standard has been defined based on the available evidence. National results will be published in an annual report and local results on a quarterly basis. The indicators will be reported as department-specific proportions with 95% confidence intervals, and the national average will be provided for comparison. An estimated 1,200-1,300 new biological therapies are initiated each year in Danish patients with IBD. CONCLUSION: The database will be available for research during 2016. Data will be made available by The Danish Clinical Registries (www.rkkp.dk).

Prevalence of maternal chronic diseases during pregnancy - a nationwide population based study from 1989 to 2013.

INTRODUCTION: There is substantial evidence of a negative impact of maternal chronic disease during pregnancy on reproductive outcomes. Knowledge of the prevalence of chronic diseases during pregnancy is limited, but essential for a focused preventive effort regarding optimal disease control during pregnancy. We aimed to analyze the prevalence of chronic diseases during pregnancy. MATERIAL AND METHODS: This register-based cohort study included all women giving birth in Denmark between 1989 and 2013 based on data from Danish health registers. Maternal chronic diseases included 23 disease categories of both physical and mental health conditions recorded within a period of 10 years before childbirth. RESULTS: We included 1 362 200 childbirths during the study period. The overall prevalence of maternal chronic disease increased from 3.71% in 1989 to 15.76% in 2013. The most frequently registered chronic diseases were chronic lung diseases/asthma (1.73%), thyroid disorders (1.50%) and anxiety and personality disorders (1.33%). Taking increasing maternal age at birth into account, the relative risk for women to have a chronic disease from 2009 to 2013 was 4.14 (95% CI 4.05-4.22), compared with mothers giving birth from 1989 to 1993. CONCLUSIONS: We found an increasing prevalence of maternal chronic disease during pregnancy and more than a four-fold increased risk of maternal chronic disease during pregnancy for childbirths in the period 2009 through 2013, compared with 1989 through 1993. The main limitation of our study is related to a potentially greater awareness and hence more careful registration of maternal chronic disease over time and thereby an increased tendency to register diseases.

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

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.

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 Crohn's 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.