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.

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.

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.

Inflammatory Bowel Disease in Adults and Elderly: The Use of Selected Non-IBD Medication Examined in a Nationwide Cohort Study.

BACKGROUND: Real-world data on medications used for conditions other than inflammatory bowel disease (IBD) are sparse. We examined how the onset of IBD affects the prescription pattern of selected non-IBD medication and the risk of becoming an incident user. METHODS: This nationwide cohort study utilized data from Danish health registers. We included incident patients with young adult-onset IBD (18-39 years of age), adult-onset IBD (40-59 years of age), and elderly-onset IBD (60+ years of age), from 1998 to 2018 and followed all for 3 years. We examined redeemed prescriptions before and after the onset of IBD and estimated the risk of becoming a user of non-IBD medications using logistic regression models. RESULTS: We identified 36165 patients, 16 771 (46%) with young adult onset, 10615 (29%) with adult onset, and 8779 (24%) with elderly onset. The onset of IBD increased the use of antidepressants, antipsychotics, sedatives/hypnotics, opioids, nonopioid analgesics, antidiabetics, and proton pump inhibitors, even in patients with no other underlying comorbid diseases. The adjusted odds ratio for using antidepressants 1 year after the onset of IBD in elderly was 1.50 (95% confidence interval [CI], 1.14-1.82), in opioids 1.69 (95% CI, 1.45-1.95), in nonopioid analgesics 2.10 (95% CI, 1.77-2.48), in cardiovascular medication 2.20 (95% CI, 1.86-2.61), and in proton pump inhibitors 1.51 (95% CI, 1.31-1.74) compared with adults. CONCLUSIONS: In all 3 age groups, the proportions of patients with redeemed prescriptions for several groups of non-IBD medication were significantly increased after the IBD diagnosis compared with before. The risk of becoming an incident user for several groups of non-IBD medication was increased in elderly patients.

In patients with young adult onset, adult onset, and elderly onset of inflammatory bowel disease (IBD), the proportions of prescriptions for non-IBD medication was significantly increased after the IBD onset compared with before. The risk of new use of non-IBD medication was increased in elderly-onset IBD patients.

Common factors, Responsiveness and Outcome in Psychotherapy (CROP): study protocol for a naturalistic prospective cohort study of psychotherapy in Denmark.

INTRODUCTION: The aim of the Common factors, Responsiveness and Outcome in Psychotherapy (CROP) study is to identify client and psychologist characteristics and therapeutic processes associated with the outcome of psychotherapy delivered by psychologists employed in the Danish primary sector or fully self-employed. The study addresses two main questions. First, how are specific characteristics of clients and psychologists related to the outcome of therapy and do these characteristics moderate the outcome of different psychotherapeutic approaches? Second, to what extent do therapists adapt their approach to client characteristics and preferences and how does such responsiveness impact the process and outcome of therapy? METHODS AND ANALYSIS: The study is a naturalistic prospective cohort study carried out in collaboration with psychologists in private practice in Denmark. Self-reported data are collected from the participating psychologists and their participating clients before, during (weekly and postsession) and after psychotherapy (at end of treatment and 3 months follow-up). The estimated target sample size is 573 clients. The data are analysed using multilevel modelling and structural equation modelling approaches to capture predictors and moderators of the effect and rate of change in psychotherapy as well as session-to-session changes during the therapy process. ETHICS AND DISSEMINATION: The study has been approved by the IRB at the Department of Psychology, University of Copenhagen (IRB number: IP-IRB/01082018) and the Danish Data Protection Agency. All study data are fully anonymised and all clients have given informed consent to participation in the study. The study findings will be presented in articles in international, peer-reviewed journals as well as to psychotherapy practitioners and other professionals across Denmark. TRIAL REGISTRATION NUMBER: NCT05630560.

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.

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.

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.

Long-term consistency in susceptibility of prey species to predation by an avian predator.

Selection by predators affects prey through competition for limiting resources. This not only has consequences for direct mortality but also indirectly affects disturbance. Changes in the intensity of selection on prey by predators may affect the size of prey populations, with consequences for their short- or long-term interactions. We assessed whether predation by northern goshawks Accipiter gentilis modified the composition of prey communities consistently along a temporal gradient, showing long-term consistency in susceptibility of prey species to predation. We followed six populations of the goshawk in two biomes in Denmark and Finland during 1949-2019. Susceptibility to goshawk predation in 2005-2017 in Denmark was only weakly related to susceptibility to goshawk predation in 1977-2004. In Finland, susceptibility of shared prey species to goshawk predation was positively related between periods. The average difference in susceptibility to goshawk predation between periods was considerably higher in Denmark than in Finland. Susceptibility of prey species to predation in goshawks increased with latitude and body mass of prey species, and decreased with period of time and population density of prey species. The changes in susceptibility to predation suggest changes in the characteristics of the local prey pools.

Diabetes mellitus and the risk of post-acute COVID-19 hospitalizations-a nationwide cohort study.

AIMS: This cohort study, based on Danish health registers, examined the post-acute consequences of hospitalization for COVID-19 in patients with diabetes. METHODS: The study population comprised all Danish citizens (≥18 years old) who had diabetes when the pandemic started. A patient was exposed if he/she had a hospitalization with COVID-19 after 1 March 2020. A patient was unexposed when he/she was not hospitalized with COVID-19 between 1 March 2020 and the end of follow-up (4 January 2022), or the first registered event of interest. The outcomes included post-COVID-19 hospitalizations and death. We used a Cox proportional hazards model with time varying exposure estimating the hazards ratio (HR) to analyze if the hazard for an outcome of interest was impacted by being hospitalized with COVID-19. RESULTS: In patients with type 1 diabetes, 101 were hospitalized with COVID-19, and 25,459 were not. We did not have sufficient statistical power to identify differences in risk for those with type 1 diabetes. In type 2 diabetes, 1515 were hospitalized with COVID-19, and 95,887 were not. The adjusted HRs of post-acute hospitalization for respiratory diseases and infections were 1.71 (95% CI 1.45-2.03) and 1.87 (95% CI 1.61-2.18), respectively. The HR of death was 2.05 (95% CI 1.73-2.43). Patients with uncertain type had results similar to those with type 2 diabetes. CONCLUSIONS/INTERPRETATION: In type 2 diabetes and diabetes of uncertain type, hospitalization with COVID-19 was associated with an increased risk of post-acute hospitalization for respiratory diseases, infections and death.

Increased Risk of Postpartum Infections After Caesarian and Vaginal Delivery in Women With Inflammatory Bowel Disease: A Danish Nationwide Cohort Study.

BACKGROUND: There is lack of knowledge concerning postpartum infections in women with inflammatory bowel disease (IBD). Our aim is to determine the 30-day postpartum infectious complications in women with and without IBD who have a caesarian section, normal vaginal delivery, or assisted vaginal delivery. METHODS: We used Danish national registries to establish a study population of liveborn, singleton births from January 1, 1997, through December 31, 2015. We examined 30-day postpartum maternal infectious complications in women with and without IBD, according to the mode of delivery. Statistical models were adjusted for multiple confounders. RESULTS: In all, 3255 women with and 207 608 without IBD had a caesarian section. Within 30 days postpartum, 4.5% of women with and 3.7% without IBD had an infectious complication. Increased infectious complications included overall infections (adjusted OR [aOR], 1.83; 95% confidence interval [CI], 1.35-2.47), infections of the gastrointestinal tract (aOR, 4.36, 95% CI 2.34-8.10), and infections of the skin and subcutaneous tissue (aOR, 4.45; 95% CI, 2.30-8.50). Other puerperal infections, urological and gynecological, and other infections were increased, although not significantly. For vaginal deliveries, 1.6% of 5771 women with IBD and 1.3% of 793 110 women without IBD had an infectious complication, and the aOR of infections of the gastrointestinal tract was 3.17 (95% CI, 1.47-6.85). There were too few outcomes to calculate the risk of infections after assisted vaginal delivery. CONCLUSIONS: The risk of a 30-day postpartum infectious complication is increased in women with IBD. Physicians should carefully monitor their patients postpartum to prevent these adverse outcomes.

Women with inflammatory bowel disease who have a caesarean section or a vaginal delivery are at increased risk for infections within the 30-day postpartum period. Physicians should be aware of this increased risk and work to minimize infectious complications after delivery.

Adverse Birth and Child Outcomes in Children Fathered by Men Treated with Antidiabetics Prior to Conception: A Nationwide Cohort Study.

BACKGROUND: The safety of fathers' use of antidiabetic drugs in terms of child outcomes is an important clinical question. We aimed to assess the risk of adverse birth and early childhood outcomes after fathers' use of antidiabetics prior to conception. METHODS: A nationwide cohort study based on Danish health registries. The study comprised all live born singleton children in Denmark (1997 through 2018). Children were categorized according to fathers' filled prescriptions for antidiabetic drugs three months prior to conception. Exposed cohorts: children born after paternal use of insulin or non-insulin anti-hyperglycemic agents. The unexposed constituted children born by fathers not treated with antidiabetics prior to conception. We examined adverse birth outcomes (preterm birth, small for gestational age (SGA)), and adverse childhood outcomes in the first year of life (major congenital malformations (MCMs), and infections diagnosed at a hospital). RESULTS: A total of 1,318,684 children were included. In all, 5527 children were born after paternal use of insulin, 2121 after use of non-insulin anti-hyperglycemic agents, and 1,311,036 were unexposed. After fathers' use of insulin we did not find increased risk of adverse outcomes. After fathers' use of metformin, the adjusted OR of MCMs was 1.40 (95% CI 1.11-1.76). After fathers' use of sulfonylureas, the adjusted OR of SGA was 1.80 (95% CI 1.11-2.93), and for child gastrointestinal infections the adjusted HR was 1.76 (95% CI 1.04-2.99). CONCLUSIONS: Fathers' use of insulin was reassuring. Metformin and sulfonylureas were associated with selected adverse outcomes. Our findings suggest an additional 14 MCMs per 1000 fathers exposed to metformin prior to conception. As there is no meaningful supporting biological rationale, these findings should be confirmed in a different population prior to clinical consequences being drawn.

Calibration Uncertainty of Non-Catching Precipitation Gauges.

Precipitation is among the most important meteorological variables for, e.g., meteorological, hydrological, water management and climate studies. In recent years, non-catching precipitation gauges are increasingly adopted in meteorological networks. Despite such growing diffusion, calibration procedures and associated uncertainty budget are not yet standardized or prescribed in best practice documents and standards. This paper reports a metrological study aimed at proposing calibration procedures and completing the uncertainty budgets, to make non-catching precipitation gauge measurements traceable to primary standards. The study is based on the preliminary characterization of different rain drop generators, specifically developed for the investigation. Characterization of different models of non-catching rain gauges is also included.

Effect of deliberate practice training of graduate students in general psychotherapeutic skills compared with theoretical teaching: protocol for the randomised controlled TRIPS trial.

INTRODUCTION: Psychology students at universities in Denmark and worldwide often receive relatively little clinical training, even though such training is crucial to job performance after graduation. Training common psychotherapeutic skills, such as being empathic and facilitating the therapeutic alliance, is critical since these skills are related to psychotherapy outcomes. In this study, a deliberate practice-based approach to student training will be compared with theoretical teaching. The main hypothesis is that deliberate practice training will result in a larger improvement in students' observer-rated interpersonal skills. METHODS AND ANALYSIS: The TRaining of graduate students In general Psychotherapeutic Skills study has a double-centre, randomised, assessor-blinded, two-way crossover study design. About 200 graduate students from two Danish universities will be randomised into two groups, (a) deliberate practice training of common psychotherapeutic skills using role-play and Skillsetter, an online skill-building system with therapy videos or (b) theoretical teaching. Group a will first receive the experimental condition, followed by the control condition, while group b will receive the conditions in reverse order. Each condition consists of 15 hours of classroom participation and homework. The primary outcome is facilitative interpersonal skills-observer. Secondary outcomes include the facilitative interpersonal skills-self-report, the Counselor Activity Self-Efficacy Scales and the Interpersonal Reactivity Index. Outcomes will be measured at baseline (week 0), after the first condition (week 5; before the crossover, reflecting true randomisation) and after both conditions (week 10). Main outcome analyses will be performed at week 5. Several predictors of the effect of deliberate practice will be explored. ETHICS AND DISSEMINATION: Ethical approval from university ethics boards has been obtained. All participants will be asked to provide informed consent before participation. Once completed, the study can potentially transform the training of psychotherapy in graduate education, which, ultimately, may positively influence psychotherapy outcomes (IP-IRB / 03092021). TRIAL REGISTRATION NUMBER: NCT05164497.

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.

Recurrent atrial arrhythmia in a randomised controlled trial comparing contact force-guided and contact force-blinded ablation for typical atrial flutter.

BACKGROUND: Contact force (CF)-guided catheter ablation (CA) is a novel technology developed to improve efficacy and reduce complications. In a randomised controlled trial (RCT), we previously documented that after 3 months, rate of persistent conduction block was similar with and without using CF while performing CA for typical atrial flutter (AFL). Clinical effect of CF on recurrent arrhythmia is unknown. Our objective is to study recurrent atrial arrhythmia during 12-month follow-up in a RCT investigating whether CF-guided CA for typical AFL is superior to CF-blinded CA. METHODS: Patients were randomised 1:1 to CA guided by CF (intervention group) or blinded to CF (control group). After 12 months, patients attended clinical check-up preceded by a 5-day ambulatory Holter monitor recording. Primary outcome was any recurrent atrial arrhythmia ≥ 30 s within 12 months and documented in 12-lead ECG or Holter monitor recording. RESULTS: We included 156 patients, four patients withdrew consent and two died during follow-up. Thus, 150 patients were included in final analysis. Recurrent arrhythmia was detected in 36 of 77 (47%) patients in the intervention group, and 32 of 73 patients (44%) in the control group (p = 0.51). Atrial fibrillation was detected in 23 (30%) and 29 (40%) patients in the intervention and control groups respectively. AFL was detected in 11 (14%) and 5 (7%) patients in the intervention and control groups respectively. CONCLUSIONS: Contact force-guided ablation for typical atrial flutter does not reduce recurrent atrial arrhythmia after 12-month follow-up as compared with ablation blinded for contact force.

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.