The impact of iron deficiency on patients under evaluation for colorectal cancer, a prospective cross-sectional study.

BACKGROUND AND OBJECTIVE: Iron deficiency affects more than 60% of colorectal cancer patients at the time of diagnosis. Iron deficiency ultimately leads to anemia, but additionally, iron deficiency might impact other domains of colorectal cancer patients' health and well-being. The aim of this study was to evaluate the impact of iron deficiency on fatigue, quality of life, cognition, and physical ability in patients undergoing evaluation for colorectal cancer. METHODS: Multicenter, prospective, observational cross-sectional study (2021-2023). Fatigue was the primary outcome, measured using the Focused Assessment of Cancer Treatment-Anemia questionnaire (FACT-An). Quality of Life, Cognition, Aerobe capacity, mobility, and peripheral muscle strength were tested as secondary outcomes. Multivariate analysis was performed to estimate the impact of iron deficiency on all outcomes. RESULTS: Two hundred and one patients were analyzed, 57% being iron deficient. In multivariate regression analysis, iron deficiency was not associated with fatigue: FACT-An (r = -1.17, p = 0.57, 25% CI: -5.27 to 2.92). Results on quality of life, cognition, and mobility were non-significant and with small regression coefficients. Iron deficiency showed a nearly significant association with reduced hand-grip-strength (r = -3.47 kg, p = 0.06, 25%CI -7.03 to 0.08) and reduced 6 min walking distance (r = -40.36 m, p = 0.07, 25%CI: -84.73 to 4.00). CONCLUSION: Iron deficiency in patients undergoing evaluation for colorectal cancer was not associated with fatigue, quality of life, or cognition, but might affect aerobic endurance and peripheral muscle strength to a degree that is clinically relevant.

New surgery and hospital-diagnosed infections in elderly patients with inflammatory bowel disease undergoing surgery - a nationwide cohort study.

BACKGROUND: Elderly patients with inflammatory bowel disease (IBD) are fragile in many aspects. Therefore, in these patients, we studied post-operative complications (new abdominal surgery and serious infections after the first IBD surgery). METHODS: This is a nationwide cohort study based on Danish health registries and included patients with IBD undergoing surgery. The study population was split into ulcerative colitis (UC) and Crohn's disease (CD). The exposed cohort (elderly) constituted those at an age of ≥ 60 years at first IBD surgery, and the unexposed (adults) those with surgery at the age of 18-59 years. We estimated adjusted Hazard Ratios (aHR) of a) new abdominal surgery within 2 years, and b) serious (hospital-diagnosed) infections within 6 and 12 months. We adjusted for several confounders including type of index surgery (laparoscopic or open). RESULTS: The aHR for a new surgery among elderly with UC and CD were 0.69 (95% CI 0.58-0.83) and 0.98 (95% CI 0.83-1.15), respectively. In elderly with UC, the aHRs of infections within 6 and 12 months after surgery were 1.07 (95% CI 0.81- 1.40) and 0.85 (95% CI 0.67-1.08), respectively. In the elderly with CD, the aHRs of infections within 6 and 12 months were 1.45 (95% CI 1.12-1.88) and 1.26 (95% CI 1.00-1.59), respectively. CONCLUSION: The elderly with IBD did not have an increased risk of new abdominal surgery within two years of the first surgery. Elderly with CD, but not UC, had an increased risk of serious infections within 6 months of surgery.

Does Surgery Before Pregnancy in Women With Inflammatory Bowel Disease Increase the Risk of Adverse Maternal and Fetal Outcomes? A Danish National Cohort Study.

INTRODUCTION: Up to 15% of women with Crohn's disease (CD) or ulcerative colitis (UC) undergo bowel surgery before pregnancy, and there is little data on pregnancy outcomes in this population. We aimed to assess maternal/fetal outcomes in women with CD or UC who underwent surgeries before pregnancy. METHODS: In this nationwide study, we included all pregnancies in women with CD or UC from 1997 to 2022 and examined 6 categories of CD and UC surgeries before pregnancy. We used multilevel logistic regression to compute crude and adjusted odds ratios (aOR) with 95% confidence intervals (95% CI) for the risk of pregnancy and offspring complications in women who did, vs did not, undergo surgery before pregnancy. RESULTS: There were 833 UC and 3,150 CD pregnancies with prior surgery and 12,883 UC and CD 6,972 pregnancies without surgery. For UC, prior surgery was associated with Cesarian section (C-section) (ileoanal pouch: aOR: 20.03 [95% CI 10.33-38.83]; functional ileostomy: aOR:8.55 [6.10-11.98]; diverting ileostomy: aOR: 38.96 [17.05-89.01]) and preterm birth (aOR: 2.25 [1.48-3.75]; 3.25 [2.31-4.59]; and 2.17 [1.17-4.00]) respectively. For CD and prior intestinal surgery, the risks of C-section (aOR: 1.94 [1.66-2.27]), preterm birth (aOR: 1.30 [1.04-1.61]), and low 5-minute Apgar (aOR: 1.95 [95% CI 1.07-3.54]) increased and premature rupture of membranes (aOR: 0.68 [0.52-0.89]) decreased. For CD with only prior perianal surgery, the risk of C-section (aOR: 3.02 [2.31-3.95]) increased and risk of gestational hypertension/preeclampsia/eclampsia (aOR: 0.52 [0.30-0.89]) decreased. DISCUSSION: Providers should be aware there is an increased likelihood of C-section and certain perinatal complications in patients with CD or UC surgery before pregnancy.

Adverse birth outcomes and early-life infections after in utero exposure to corticosteroids for inflammatory bowel disease: a Danish nationwide cohort study.

BACKGROUND: Systemic corticosteroids are often used to treat inflammatory bowel disease (IBD) flares during pregnancy as maintenance of disease remission is crucial to optimize pregnancy outcomes. However, there is little data regarding the effect of in utero exposure to corticosteroids on the risk of adverse birth outcomes and early-life infections in the offspring. METHODS: We used the Danish national registries to establish a nationwide cohort of all singleton live births in women with IBD from 1995 to 2015. Outcomes in children exposed in utero to corticosteroids were compared to those who were not exposed. In logistic and Cox proportional hazard regression models, we adjusted the outcomes (major congenital malformation, preterm birth, small for gestational age, low 5-min Apgar score, and infections) for confounders such as body mass index, smoking, comorbidity, and additional medical IBD treatment. RESULTS: After in utero exposure to corticosteroids at any time between 30 days prior to conception through the first trimester (n = 707), the adjusted hazard ratio of major congenital malformation was 1.28 (95% CI: 0.82-2.00) compared to children born to women with IBD, but not exposed to corticosteroids in utero (n = 9371). After in utero exposure to corticosteroids at any time during pregnancy (n = 1336), the adjusted odds ratios for preterm birth, small for gestational age, and low 5-min Apgar score were 2.45 (95% CI: 1.91-3.13), 1.21 (95% CI: 0.76-1.90), and 0.91 (95% CI: 0.33-2.52), respectively. Finally, the adjusted hazard ratio of overall infections in the first year of life was 1.14 (95% CI: 0.94-1.39). CONCLUSIONS: This nationwide cohort study suggests that children of women with IBD exposed to corticosteroids in utero had an almost 2.5-fold increased risk of preterm birth. Use of corticosteroids is closely related to disease activity and we cannot adjust for the independent role of disease activity. It is however reassuring that the other examined birth and early-life outcomes were not statistically significantly increased.

Patients with elderly onset inflammatory bowel disease have a decreased chance of initiation of all types of medications and increased risk of surgeries-A nationwide cohort study.

OBJECTIVE: In patients with elderly (≥60 years) onset inflammatory bowel disease (IBD), we studied initiation of medications, drug persistency and surgeries. DESIGN: A nationwide cohort study based on Danish registries, comprising incident IBD patients ≥18 years from 1995 to 2020 (N = 69,039). Patients were divided into elderly (N = 19,187) and adult onset (N = 49,852). Outcomes were initiation of thiopurines, 5-ASA, biologics and corticosteroids within 1 and 5 years after diagnosis, and for those who initiated medications, we estimated drug persistency. Surgeries were examined within 1 and 5 years. We used regression models controlling for covariates. RESULTS: In elderly patients, the adjusted hazard ratios (aHR) for initiating thiopurines, 5-ASA and biologics within 1 year were 0.44 (95% CI 0.42-0.47), 0.77 (95% CI 0.75-0.79) and 0.29 (95% CI 0.26-0.31) respectively. The results were similar within 5 years. In elderly patients, drug persistency for thiopurines, 5-ASA and biologics was not impaired within 5 years. The aHR of stopping steroids within 1 and 5 years were 0.80 (95% CI 0.76-0.84) and 0.77 (95% CI 0.74-0.80) respectively. The risk of surgeries was increased in the elderly patients (in ulcerative colitis, within 5 years, aHR 1.39 [95% CI 1.27-1.52], and in Crohn's disease 1.13 [95% CI 1.04-1.23]). CONCLUSION: We found significantly low chance of initiation of IBD medications in elderly patients, the reason may not be due to mild disease course. In elderly patients, drug persistency was comparable to adults. Clinicians should carefully consider whether they underuse IBD-specific medications in elderly patients, and special attention should be applied to timely discontinuation of corticosteroids.

COVID-19 Does Not Lead to an Increase in Corticosteroid Prescriptions in IBD Patients: A Nationwide Cohort Study.

BACKGROUND: It is not known whether coronavirus 2019 (COVID-19) is a trigger for disease activity in patients with inflammatory bowel diseases (IBD). In patients with IBD, we aimed to examine the association between COVID-19 infection and prescriptions of systemic and local corticosteroids (used as proxy for disease activity). METHODS: This nationwide cohort study was based on Danish health registries and included all patients in Denmark with ulcerative colitis (UC) or Crohn's disease (CD) by the start of the pandemic (March 1, 2020) and who had a positive COVID-19 polymerase chain reaction (PCR) test from March 1, 2020, to July 31, 2022. We calculated rates of corticosteroid prescriptions 6 months before and 6 months after a positive COVID-19 PCR test, and we calculated adjusted incidence rate ratios (aIRR). RESULTS: We included 30,102 patients with IBD and a positive COVID-19 test (11,159 with CD, 18,493 with UC). The aIRR for having corticosteroid prescriptions after a COVID-19 positive test was 0.85 (95% confidence interval [CI], 0.79-0.91). When we stratified for underlying disease, the aIRR for having corticosteroid after a COVID-19 positive test in UC was 0.82 (95% CI, 0.75-0.90), and in CD 0.91 (95% CI, 0.81-1.02). Stratifications according to calendar periods and age groups showed consistent results. CONCLUSIONS: An infection with COVID-19 did not result in a higher rate of filled corticosteroid prescriptions. Using corticosteroids as a proxy for disease activity, COVID-19 did not seem to trigger disease activity, which is a reassuring result for patients with IBD.

An infection with COVID-19 did not result in a higher rate of filled corticosteroid prescriptions. Using corticosteroids as a proxy for disease activity, COVID-19 did not seem to trigger disease activity, which is a reassuring result for patients with IBD.

The safety of paternal and maternal use of 5-aminosalicylic acid during conception and pregnancy: a nationwide cohort study.

BACKGROUND: Data on the safety of paternal use of 5-aminosalicylic acid (5-ASA) prior to conception are lacking, and the safety of maternal use of 5-ASA during pregnancy has not been examined in nationwide data. AIMS: To examine offspring outcomes after paternal pre-conception use of 5-ASA, and after maternal use during pregnancy METHODS: This nationwide cohort study was based on Danish health registries. The study population included live born singletons of patients with ulcerative colitis (UC) or Crohn's disease (CD). Paternal exposure included 2168 children fathered by men treated with 5-ASA, and 7732 unexposed. Maternal exposure included 3618 children exposed in utero to 5-ASA, and 7128 unexposed. The outcomes were pre-term birth, small for gestational age (SGA), low Apgar score and major congenital abnormalities (CAs) according to EUROCAT guidelines. RESULTS: The vast majority of fathers and mothers used mesalazine. In children fathered by men with UC using 5-ASA, we found no increased risk of pre-term birth, SGA or low Apgar score. The hazard ratio (HR) of CAs was 1.30 (95% CI 0.92-1.85). In children of fathers with CD, the odds ratio (OR) of SGA was 1.52 (95% CI 0.65-3.55). After maternal 5-ASA exposure, the OR of SGA in children of women with UC was 1.46 (95% CI: 0.93-2.30); for CAs in children of women with CD, HR was 1.44 (95% CI 0.84-2.47). CONCLUSIONS: Paternal and maternal use of 5-ASA was safe across offspring outcomes; none of the findings reached statistical significance. The safety of 5-ASA formulations that are used infrequently cannot be settled here.

Paternal use of medications for inflammatory bowel disease and the risk of hospital-diagnosed infections in the offspring: a nationwide cohort study.

BACKGROUND: Information regarding the impact of paternal inflammatory bowel disease (IBD) medications on child outcomes is scarce. AIM: To examine the risk of childhood infections associated with fathers' use of anti-inflammatory/immunosuppressive medications taken before conception. METHODS: This is a nationwide cohort study based on Danish health registries, comprising all live-born singleton children born between January 1997 and February 2019 who were fathered by men with IBD. Exposed cohorts included children fathered by men treated with 5-aminosalicylates (5-ASAs), thiopurines, corticosteroids or anti-tumour necrosis factor-α (anti-TNF-α) agents within 3 months before conception. The unexposed cohort included children not exposed to paternal IBD medications. Outcomes were the first infection, diagnosed in the hospital setting in the first year of life, and from the age of 1 to 3 years. RESULTS: In all, 2178 children were fathered by men exposed to 5-ASAs, 843 to thiopurines, 417 to systemic corticosteroids and 436 to anti-TNF-α agents; 6799 children were unexposed. The adjusted hazard ratio (aHR) for infections within the first year of life for 5-ASAs was 0.78 (95% CI, 0.66-0.91), thiopurines 0.89 (95% CI, 0.73-1.09), systemic corticosteroids 0.95 (95% CI, 0.70-1.29), and anti-TNF-α agents 1.17 (95% CI, 0.94-1.46). The aHR for infections from 1 to 3 years for 5-ASAs was 0.97 (95% CI, 0.83-1.13), thiopurines 0.87 (95% CI, 0.71-1.07), systemic corticosteroids 1.25 (95% CI, 0.94-1.65), and anti-TNF-α agents 0.79 (95% CI, 0.60-1.03). CONCLUSION: Fathers' use of anti-inflammatory/immunosuppressive medications before conception was not significantly associated with childhood infections. These results fill an important research gap regarding paternal medication safety.

Infliximab Is Not Associated With a General Long-Term Weight Gain in Patients With Inflammatory Bowel Disease: A Nationwide Study.

INTRODUCTION: Patients with Crohn's disease (CD) and ulcerative colitis (UC) may lose weight during periods of active disease and may gain weight when inflammation heals. Studies have hypothesized an association between antitumor necrosis factor-alpha (anti-TNF-α) and unintended weight gain during maintenance therapy, and this association has not been previously clarified. METHODS: In a nationwide observational study based on Danish national health registries, we included patients who initiated therapy with infliximab and followed changes in weight during induction therapy (0-90 days) and maintenance therapy (91-270 days). The association between the use of infliximab and weight gain was analyzed by a multilevel mixed-effects linear regression model. RESULTS: Among 851 patients with CD and UC who initiated infliximab therapy, long-term weight gain was not observed during maintenance therapy in most of the patients. Women with CD who were underweight at the initiation of therapy had an average weight gain of 7.5 kg. Men and women with CD and UC with normal or increased body mass index had an average weight gain of <2 kg during maintenance therapy. Underweight men with CD and UC gained 2.9 kg (95% confidence interval 2.1-3.6) and 2.9 kg (95% confidence interval 1.9-3.9), respectively, in the first 90 days, although neither group had statistically significant weight gain in the maintenance period. Less than 3% of the patients had weight gain greater than 10% of their baseline body weight during the study period. DISCUSSION: Weight gain among patients treated with anti-TNF-α therapies is unlikely to be due to an effect from anti-TNF-α therapy.

Postpartum Surgical Complications in Women with Inflammatory Bowel Disease After Caesarian Section: A Danish Nationwide Cohort Study.

BACKGROUND AND AIMS: Our aim is to determine the 30-day postpartum surgical complications in women with inflammatory bowel disease [IBD] who undergo a caesarian section rather than a vaginal delivery. METHODS: Using the Danish national registries, we established a study population of liveborn singleton births from January 1, 1997, through December 2015. We examined all mothers with IBD who had a caesarian section or a vaginal delivery. We examined 30-day maternal postpartum abdominal and perineal surgical outcomes and adjusted for multiple confounders. We examined acute versus elective caesarian sections and the effect of immunosuppressive therapies on outcomes. RESULTS: In women with IBD, 2.1% undergoing caesarian section [n = 3255] versus 0.3% undergoing vaginal delivery [n = 6425] had a surgical complication. Women with IBD who had a caesarian section were more likely to have small bowel and colon surgery (adjusted odds ratio [aOR] 5.00, 95% confidence interval [CI] 2.00-12.51). Similar results were found regardless of acute [aOR 4.51, 95% CI 1.48-13.76] or elective [aOR 6.52, 95% CI 2.45-17.33] caesarian section. The risk of surgery after caesarian section was increased regardless of immunosuppressive use [aOR with immunosuppressives 8.79, 95% CI 2.86-27.05; and aOR without immunosuppressives 4.49, 95% CI 1.74-11.58]. CONCLUSIONS: The risk of a surgical complication after caesarian section as compared with a vaginal delivery is increased in women with IBD, regardless of whether the caesarian is performed for acute or elective reasons and/or of immunosuppressive use before delivery. Due to this increased risk, physicians should perform a caesarian delivery as the exception rather than the rule.

Mesalazine in Inflammatory Bowel Disease and COVID-19: Hospitalization and Adverse In-Hospital Outcomes Based on Nationwide Data.

BACKGROUND: We assessed whether 5-aminosalicylic acid (5-ASA), as treatment for inflammatory bowel disease (IBD), was associated with an increase in hospitalization for coronavirus disease 2019 and adverse in-hospital outcomes. METHODS: This was a Danish nationwide register study. The study population consisted of all patients with an IBD diagnosis between March 1, 2010, and March 1, 2020, and living in Denmark on March 1, 2020. Patients with IBD treated with 5-ASA (exposed) were compared with patients not receiving 5-ASA (unexposed). RESULTS: We identified 60 242 patients with IBD; 15 635 (40.5%) with ulcerative colitis (UC) and 964 (4.5%) with Crohn's disease (CD) were exposed to 5-ASA. For patients with UC who were 5-ASA exposed, the hazard ratio of hospitalization was 1.18 (95% confidence interval, 0.79-1.78). In-hospital outcomes were not statistical significant from those not exposed to 5-ASA (median length of hospital stay 5.6 days vs 7.2 days), mechanical ventilation (0% vs 14%), continuous positive airway pressure (7.9% vs 9.4%), and in-hospital mortality (21.1% vs 17.2%). For patients with CD, the hazard ratio of hospitalization was 2.25 (95% confidence interval, 1.02-4.97). We found no statistically significant difference in length of hospital stay (7.1 days vs 3.9 days), mechanical ventilation (0% vs 1.8%), use of continuous positive airway pressure (0% vs 1.8%), or in-hospital mortality (0% vs 9%) between exposed and unexposed patients. CONCLUSIONS: Patients with UC, treated with 5-ASA, had no increased risk of hospitalization for coronavirus disease 2019 or more adverse in-hospital outcomes. In patients with CD, 5-ASA may be associated with an increased risk of hospitalization but not with more adverse in-hospital outcomes.

In this national register study, 5-aminosalicylic acid (5-ASA)­treated ulcerative colitis patients had no increased risk of hospitalization for coronavirus disease 2019 (COVID-19) or more adverse in-hospital outcomes compared with patients not treated with 5-ASA. Also, 5-ASA­treated patients with Crohn's disease did not have more adverse in-hospital outcomes.

Post COVID-19 hospitalizations in patients with chronic inflammatory diseases - A nationwide cohort study.

OBJECTIVE: To study long term consequences of hospitalization for COVID-19 in patients with chronic inflammatory diseases. We studied the risk of subsequent hospitalizations in patients with chronic inflammatory diseases, who survived a hospitalization for COVID-19, compared to other patients who had been hospitalized for COVID-19. DESIGN AND SETTING: Population based cohort study based on Danish nationwide health registers. The study population included all adult patients in Denmark who had been discharged alive after a hospitalization with COVID-19 from March 1, 2020 to July 31, 2021. POPULATION: From the study population, the exposed cohort constituted patients who had inflammatory bowel diseases (IBD), rheumatoid arthritis (RA), spondyloarthropathy (SpA), or psoriatic arthritis (PsA) prior to hospitalization for COVID-19, and the unexposed cohort constituted those without these diseases. MAIN OUTCOME MEASURES: We estimated the adjusted Hazard Rate (aHR) for the following outcomes: overall risk of hospitalization, cardiovascular diseases, respiratory diseases, blood and blood-forming organs, nervous system diseases, infections, sequelae of COVID-19, and death. RESULTS: A total of 417 patients with IBD/RA/SpA/PsA were discharged alive after COVID-19, and 9,248 patients without these diseases. Across the different outcomes examined, the median length of follow up was 6.50 months in the exposed cohort (25-75% percentiles: 4.38-8.12), and among the unexposed the median time of follow up was 6.59 months (25-75% percentiles: 4.17-8.49). Across different analyses, we consistently found a significantly increased risk of hospitalizations due to respiratory diseases (aHR 1.27 (95% CI 1.02-1.58)) and infections (aHR 1.55 (95% CI 1.26-1.92)). In sensitivity analyses, the overall risk of hospitalization was aHR 1.15 (95% CI 0.96-1.38) and the risk of hospitalization due to cardiovascular diagnoses was aHR 1.14 (95% CI 0.91-1.42). During the time of follow up, the risk of nervous system diagnoses or death was not increased in patients with IBD/RA/SpA/PsA. CONCLUSIONS: After hospitalization with COVID-19, patients with IBD/RA/SpA/PsA had an increased risk of subsequent hospitalizations for a number of categories of diseases, compared to other patients who have been hospitalized with COVID-19. These results are disturbing and need to be examined further. The implication of our results is that clinicians should be particularly alert for post COVID-19 symptoms from several organ systems in patients with IBD/RA/SpA/PsA.

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.

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.

In utero exposure to thiopurines/anti-TNF agents and long-term health outcomes during childhood and adolescence in Denmark.

BACKGROUND: Data on long-term health outcomes of children exposed in utero to thiopurines and anti-TNF medications are lacking. AIMS: To examine the association between in utero exposure to thiopurines and anti-TNF medications and child health outcomes of site-specific groups of infections, using a composite endpoint including psychiatric diagnoses/autism spectrum disorder (ASD)/attention deficit hyperactivity disorder (ADHD), and malignancies during childhood/adolescence. METHODS: A nationwide cohort study based on Danish health registries included 1 311 009 live born children during 1995 through 2015. Outcomes were based on hospital diagnoses (in-patients/out-patients/emergency department contacts). RESULTS: In total, 1048 children were exposed in utero to thiopurines and 1 309 961 were unexposed. The adjusted hazard ratios (HRs) for site-specific groups of infections in the first 3 years of life were close to unity. The adjusted HR of psychiatric diagnoses/ASD/ADHD was 1.11 (95% CI 0.81-1.52). The HR of malignancies was not calculated (only two events among the exposed). In total, 493 children were exposed in utero to anti-TNF medications and 728 055 were unexposed. Within the first year of life, the adjusted HR of respiratory, urological/gynaecological infections and other infections were 1.34 (95% CI 1.03-1.74), 2.36 (95% CI 1.15-4.81) and 1.61 (95% CI 1.21-2.13), respectively. We found no increased risk of other adverse outcomes. CONCLUSIONS: After in utero exposure to thiopurines, we found no increased risk of infections, psychiatric diagnoses/ASD/ADHD, or malignancies during childhood/adolescence. After in utero exposure to anti-TNF medications, the risk of respiratory, urological/gynaecological infections and other infections was increased during the first year of life.

Sexual Health in Women with Inflammatory Bowel Disease in the Danish National Birth Cohort.

BACKGROUND AND AIMS: Previous studies indicate an increased risk of sexual dysfunction in women with inflammatory bowel disease [IBD] but none have examined sexual function in a large population-based cohort. METHODS: To investigate the risk of sexual dysfunction in women with IBD, we used data from the Danish National Birth Cohort, a nationwide study of 92 274 pregnant women recruited during 1996-2002. We performed a cross-sectional study based on mothers who participated in the Maternal Follow-up in 2013-14. The outcome was self-reported sexual health. Information regarding demographics and IBD characteristics was retrieved from the Danish National Patient Register. Using regression models and adjusting for important confounders, we compared sexual function in women with and without IBD. RESULTS: The study population consisted of 38 011 women including 196 [0.5%] with Crohn's disease [CD] and 409 [1.1%] with ulcerative colitis [UC]. Median age was 44 years. Compared to women without IBD, women with UC did not have significantly decreased sexual function, while women with CD had more difficulty achieving orgasm (adjusted odds ratio [aOR] 1.53; 95% confidence interval [CI] 1.02-2.30], increased dyspareunia [aOR 1.71; 95% CI 1.11-2.63] and deep dyspareunia [aOR 2.00; 95% CI 1.24-3.22]. The risk for difficulty achieving orgasm and deep dyspareunia was further increased within 2 years of an IBD-related contact/visit [aOR 1.81; 95% CI 1.11-2.95; and aOR 2.37; 95% CI 1.34-4.19]. CONCLUSIONS: Women with CD have significantly increased difficulty achieving orgasm and increased dyspareunia. Physicians should be cognizant of and screen for sexual dysfunction in this group of patients.

Comparison of Time to Pregnancy in Women With and Without Inflammatory Bowel Diseases.

BACKGROUND & AIMS: Patients are often diagnosed with inflammatory bowel diseases (IBD) during their peak reproductive years. We investigated how IBD affects fertility in a population study of women in Denmark. METHODS: We collected data from the Danish National Birth Cohort, a nationwide study of 92,274 pregnant women recruited from 1996 through 2002. Women who had been actively trying to conceive reported their time to pregnancy through a computer-assisted telephone interview at approximately 16 weeks of gestation. Information regarding IBD was retrieved from the Danish National Patient Register. Using regression models and adjusting for important confounders, we compared time to pregnancy in women with and without IBD. RESULTS: We calculated time to pregnancy for 74,471 pregnancies in women without IBD, 340 pregnancies in women with ulcerative colitis (UC), and 206 pregnancies in women with Crohn's disease (CD). Compared to non-IBD pregnancies, the adjusted relative risk ratios for time to pregnancy of more than 12 months in women with IBD, UC, and CD were 1.28 (95% CI, 0.99-1.65), 1.10 (95% CI, 0.80-1.51), and 1.54 (95% CI, 1.03-2.30), respectively. The adjusted relative risk ratio was 2.54 (95% CI, 1.39-4.65) for a time to pregnancy of more than 12 months in women who had CD surgery prior to conception vs non-IBD pregnancies. There were too few patients with UC with surgery prior to conception to perform meaningful analyses of this group. CONCLUSIONS: In a study of women with IBD not confounded by voluntary childlessness, we found that women with CD, especially those who have undergone surgery, have a significant increase in time to pregnancy compared to women without IBD. This indicates reduced fertility in subgroups of women with IBD.

Exploratory analyses of the Danish Palliative Care Trial (DanPaCT): a randomized trial of early specialized palliative care plus standard care versus standard care in advanced cancer patients.

BACKGROUND: Early and integrated specialized palliative care is often recommended but has still only been investigated in relatively few randomized clinical trials. OBJECTIVE: To investigate the effect of early specialized palliative care plus standard care versus standard care on the explorative outcomes in the Danish Palliative Care Trial (DanPaCT). METHODS: We conducted a randomized multicentre, parallel-group clinical trial. Consecutive patients with metastatic cancer were included if they had symptoms or problems that exceeded a predefined threshold according to the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30). Outcomes were estimated as the differences between the intervention and the control groups in the change from baseline to the weighted mean of the 3- and 8-week follow-ups measured as areas under the curve. RESULTS: In total, 145 patients were randomized to early specialized palliative care plus standard care versus 152 to standard care only. Early specialized palliative care had no significant effect on any of the symptoms or problems. Of the 21 items addressing satisfaction, specialized palliative care improved the item 'overall satisfaction with the help received from the health care system' with 9 points (95% confidence interval 3.8 to 14.2, p = 0.0006) and three other items (all p < 0.05). CONCLUSION: In line with the analyses of the primary and secondary outcomes in DanPaCT, we did not find that specialized palliative care, as provided in DanPaCT, affected symptoms and problems. However, patients in the intervention group seemed more satisfied with the health care received than those in the standard care group. TRIAL REGISTRATION: NCT01348048.

Increased risk of developing Crohn's disease or ulcerative colitis in 17 018 patients while under treatment with anti-TNFα agents, particularly etanercept, for autoimmune diseases other than inflammatory bowel disease.

BACKGROUND: Anti-TNFα agents have revolutionised management of chronic inflammatory diseases. Paradoxically, these agents might provoke development of de novo autoimmune diseases. AIM: To examine whether there is an increased risk of developing Crohn's disease (CD) and ulcerative colitis (UC) while under treatment with anti-TNFα agents for diseases other than inflammatory bowel disease (IBD) METHODS: A nationwide cohort study, based on Danish health registries, of all patients who utilised anti-TNFα agents for non-IBD indications. Included were patients, who had diseases for which anti-TNFα agent is indicated (rheumatoid arthritis, psoriasis/psoriatic arthritis, ankylosing spondylitis, others). The observation period for development of de novo IBD started from 2004. Exposed patients had received at least one dose of anti-TNFα. RESULTS: In total 17 018 individuals with autoimmune diseases were exposed to anti-TNFα (the vast majority had infliximab, etanercept and adalimumab), and 63 308 individuals were not. Patients treated with etanercept had an increased risk of being diagnosed with CD and UC while under treatment, adjusted hazard ratio 2.0 [95% CI: 1.4-2.8] and 2.0 [95% CI: 1.5-2.8], respectively. The corresponding hazards ratios for infliximab were 1.3 [95% CI: 0.8-2.2] and 1.0 [95% CI:0.6-1.6], and for adalimumab 1.2 [95% CI: 0.8-1.8] and 0.6 [95% CI: 0.3-1.0]. CONCLUSIONS: Patients treated for autoimmune diseases with anti-TNFα had an increased risk of being diagnosed with CD or UC while under treatment with etanercept. The nature of this association is uncertain. This finding has relevance to clinical care and insights into common mechanisms of the pathophysiology of these diseases.