Paternal use of selective serotonin reuptake inhibitors and adverse health outcomes: A nationwide cohort study on 13,547 exposed children.

BACKGROUND: The use of selective serotonin reuptake inhibitors (SSRIs) has increased over time. Several studies indicate that paternal use of medication may adversely affect the developing fetus. Only a few studies have investigated the association between preconceptional paternal exposure to SSRIs and the risks of adverse health outcomes in children. OBJECTIVES: This study aimed to assess adverse birth outcomes and adverse early life events in children fathered by men using SSRIs prior to conception. MATERIALS AND METHODS: All live-born singleton children born in Denmark from 1997 until 2019 and their parents were included. The exposed cohort comprised all children fathered by men using SSRIs 3 months prior to conception and the unexposed cohort comprised all other children. We estimated the odds ratios for adverse birth outcomes: small for gestational age (SGA), preterm birth, low Apgar score, and major congenital malformations. Furthermore, we estimated the hazard ratios for adverse early life events of infections and hospitalizations within 1 year from birth. We also examined adverse birth outcomes and the adverse early life events according to SSRI subgroups. RESULTS: There was a statistically significantly increased odds ratio 1.15 (confidence interval, CI: 1.06-1.23) for preterm birth. No significant results were found for SGA, low Apgar score, and major congenital malformations. The adjusted hazard ratios for hospitalizations and infections were 1.06 (CI: 1.02-1.11) and 1.02 (CI: 0.97-1.07), respectively. There was a statistically significantly increased odds ratio for preterm birth with respect to the SSRI subgroups citalopram and escitalopram, and for hospitalizations with respect to citalopram. DISCUSSION AND CONCLUSION: Although the risks of certain adverse birth and adverse early life outcomes were statistically significantly increased, the ratios were small and may have limited clinical importance. Paternal use of SSRI was in general safe in the preconceptual period.

Neonatal outcomes in women with Multiple Sclerosis - Influence of disease activity: A Danish nationwide cohort study.

BACKGROUND: Maternal Multiple Sclerosis (MS) has been associated with an increased risk of adverse birth outcomes. We hypothesized that active disease during conception and pregnancy plays an important role in this context, which this study aims to address. METHODS: We used the Danish registers to conduct a nationwide cohort study. Information on maternal disease activity during pregnancy was retrieved using proxies from the linked registers (hospitalization, magnetic resonance imaging of the brain, and use of systemic corticosteroids during pregnancy). Neonates, exposed in utero to maternal disease activity constituted the exposed cohort and the unexposed cohort constituted neonates without in utero exposure to maternal disease activity. The examined outcomes were preterm birth, small for gestational age, low 5-minute Apgar score, and major congenital anomalies. In logistic regression models we estimated the odds ratios (OR) with adjustment for confounders such as maternal age, comorbidities, parity, smoking, calendar year of birth, and disease-modifying treatment. RESULTS: Among the study population of 2492 children of mothers with MS we identified 273 (11 %) neonates exposed to maternal disease activity during pregnancy, and 2219 (89 %) neonates without exposure to disease activity. The adjusted odds ratios (aOR) for preterm birth, small for gestational age, low 5-minute Apgar score, and major congenital anomalies among children born to women with disease activity during pregnancy were 0.92 (95 % confidence interval (95 % CI) 0.53-1.60), aOR 1.19 (95 % CI 0.62-2.26), aOR 2.57 (95 % CI 0.93-7.15) and aOR 0.93 (95 % CI 0.48-1.83), respectively. CONCLUSIONS: Women with MS having disease activity during pregnancy did not have a statistically significantly increased risk of adverse neonatal outcomes compared to women with MS without disease activity, which is overall reassuring results. We believe, that this will be useful knowledge for patients and clinicians in planning a pregnancy and preparing a birth plan.

Prevalence estimates of tuberculosis infection in adults in Denmark: a retrospective nationwide register-based cross-sectional study, 2010 to 2018.

BackgroundTuberculosis (TB) elimination requires identifying and treating persons with TB infection (TBI).AimWe estimate the prevalence of positive interferon gamma release assay (IGRA) tests (including TB) and TBI (excluding TB) in Denmark based on TBI screening data from patients with inflammatory bowel disease (IBD) or inflammatory rheumatic disease (IRD).MethodsUsing nationwide Danish registries, we included all patients with IBD or IRD with an IGRA test performed between 2010 and 2018. We estimated the prevalence of TBI and positive IGRA with 95% confidence intervals (CI) in adolescents and adults aged 15-64 years after sample weighting adjusting for distortions in the sample from the background population of Denmark for sex, age group and TB incidence rates (IR) in country of birth.ResultsIn 13,574 patients with IBD or IRD, 12,892 IGRA tests (95.0%) were negative, 461 (3.4%) were positive and 221 (1.6%) were indeterminate, resulting in a weighted TBI prevalence of 3.2% (95% CI: 2.9-3.5) and weighted positive IGRA prevalence of 3.8% (95% CI: 3.5-4.2) among adults aged 15-64 years in the background population of Denmark. Unweighted TBI prevalence increased with age and birthplace in countries with a TB IR higher than 10/100,000 population.ConclusionEstimated TBI prevalence is low in Denmark. We estimate that 200,000 persons have TBI and thus are at risk of developing TB. Screening for TBI and preventive treatment, especially in persons born in high TB incidence countries or immunosuppressed, are crucial to reduce the risk of and eliminate TB.

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.

Longitudinal Measurements of Blood Biomarkers in Patients with Crohn's Disease or Ulcerative Colitis Treated with Infliximab: Only the Latest Values in the Induction Period Predict Treatment Failure.

Background: Few studies have incorporated longitudinal assessments or used combinations of blood biomarkers as predictors of loss of response to biologic therapy for patients with Crohn's disease (CD) or ulcerative colitis (UC). Methods: This is a population-based cohort study comprising Danish patients with CD or UC from 2008 to 2018. We used logistic regression to analyze whether levels and changes in levels of C-reactive protein (CRP), serum albumin, and hemoglobin, routinely measured during a 14-week infliximab induction period, predicted a change to another biologic medication or cessation of biologic therapy. Results: During the induction period, 2883 (1626 CD, 1257 UC) patients had 12,730, 12,040, and 13,538 specimens with CRP, serum albumin, and hemoglobin, respectively. In all, 284 patients (9.9%) switched to another biologic medication, and 139 (4.8%) ceased biologic therapy in the follow-up period. Only the most recent CRP and hemoglobin levels predicted the efficacy of infliximab treatment at approximately 14 weeks, a time point when the clinician often determines whether to continue treatment. Conclusion: Measurement of blood biomarkers prior to the clinical assessment does not predict the effectiveness of infliximab.

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.

Older Adult-Onset of Inflammatory Bowel Diseases Is Associated With Higher Utilization of Analgesics: A Nationwide Cohort Study.

INTRODUCTION: Patients with inflammatory bowel diseases (IBD) commonly require analgesic medications to treat pain, which may be associated with complications. We examined trends of analgesic use according to age at IBD onset. METHODS: This nationwide cohort study included adults diagnosed with IBD between 1996 and 2021 in Denmark. Patients were stratified according to their age at IBD onset: 18-39 years (young adult), 40-59 years (adult), and older than 60 years (older adult). We examined the proportion of patients who received prescriptions for analgesic medications within 1 year after IBD diagnosis: strong opioids, tramadol, codeine, nonsteroidal anti-inflammatory drugs, and paracetamol. Multivariable logistic regression analysis was performed to examine the association between age at IBD onset and strong opioid prescriptions and the composite of strong opioid/tramadol/codeine prescriptions. RESULTS: We identified 54,216 adults with IBD. Among them, 25,184 (46.5%) were young adults, 16,106 (29.7%) were adults, and 12,926 (23.8%) were older adults at IBD onset. Older adults most commonly received analgesic prescriptions of every class. Between 1996 and 2021, strong opioid, tramadol, and codeine prescriptions were stable, while paracetamol prescriptions increased and nonsteroidal anti-inflammatory drug prescriptions decreased. After multivariable logistic regression analysis, older adults had higher adjusted odds of receiving strong opioid prescriptions (adjusted odds ratio 1.95, 95% confidence interval 1.77-2.15) and the composite of strong opioid/tramadol/codeine prescriptions (adjusted odds ratio 1.93, 95% confidence interval 1.81-2.06) within 1 year after IBD diagnosis compared with adults. DISCUSSION: In this nationwide cohort, older adults most commonly received analgesic prescriptions within 1 year after IBD diagnosis. Additional research is needed to examine the etiology and sequelae of increased analgesic prescribing to this demographic.

Paternal preconception exposure to non-steroid anti-inflammatory drugs or opioids and adverse birth outcomes: A nationwide registry-based cohort study.

BACKGROUND AND AIM: Paternal use of analgesics during the time of conception and adverse birth outcomes are poorly studied. We investigated the association between paternal exposure to non-steroid anti-inflammatory drugs and opioids within 3 months before the date of conception and the risk of adverse birth outcomes (preterm birth, small for gestational age, low Apgar score, and major congenital malformations). METHODS: We used nationwide data from the Danish health registers. We included information on all singleton live births, and their fathers and mothers from 1997 to 2018. We created two exposed cohorts, children with preconception paternal exposure to (1) non-steroid anti-inflammatory drugs and (2) opioids. The unexposed cohort was children without preconception paternal exposure to non-steroid anti-inflammatory drugs or opioids, and we performed a sub-analysis against paternal use of acetaminophen (paracetamol). We used logistic regression models to estimate the odds ratios of adverse birth outcomes including 95% confidence intervals. RESULTS: We identified 1,260,934 children, 45,667 children with paternal exposure to non-steroid anti-inflammatory drugs, 10,086 children with paternal exposure to opioids, and 1,205,181 unexposed children. The adjusted odds ratio for preterm birth was 1.08 (95% confidence interval, 1.03-1.13) after paternal exposure to non-steroid anti-inflammatory drugs and 1.21 (95% confidence interval, 1.08-1.35) after paternal exposure to opioids. The adjusted odds ratio for small for gestational age was 1.09 (95% confidence interval, 1.03-1.17) after paternal exposure to non-steroid anti-inflammatory drugs, and 1.03 (95% confidence interval, 0.88-1.21) after paternal exposure to opioids. We found null-associations for a low Apgar score and major congenital malformations. Estimates were attenuated when compared against paternal paracetamol exposure. CONCLUSIONS: Overall, we found null-associations across the comparisons made. Weak associations were found for paternal exposure to non-steroid anti-inflammatory drugs or opioids and preterm birth and small for gestational age, but not with low Apgar score or major congenital malformation. All associations were attenuated when compared against an active comparator of paternal paracetamol exposure. The effect sizes were small and less likely to be of clinical relevance.

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.

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.

Patients with multiple sclerosis: COVID-19 related disease activity and hospitalisations based on a nationwide cohort study.

BACKGROUND: It has not previously been clarified if COVID-19 triggers disease activity and increases the risk of hospitalisation with COVID-19 in patients with multiple sclerosis. We examined the association between COVID-19 and the use of systemic corticosteroids prescriptions and hospital contacts at neurological departments as proxies of disease activity among patients with multiple sclerosis. Furthermore, we examined whether patients with multiple sclerosis were more likely to be hospitalised with COVID-19 compared to references. METHODS: This study was based on nationwide health registries with data on the Danish population of 2,222,946 individuals with a positive COVID-19 PCR test. To study disease activity our study population consisted of all patients with multiple sclerosis and a positive COVID-19 PCR test. Our proxies for disease activity were compared after versus before a positive COVID-19 PCR test using a binomial regression model. Adjustments were made for age, sex, comorbidity, length of multiple sclerosis diagnosis, calendar period, vaccination, and immunomodulatory treatment. To study the risk of hospitalisation with COVID-19 in patients with multiple sclerosis our study population here consisted of all Danish citizens with a COVID-19 positive PCR test. In logistic regression models we estimated odds ratio (OR) for hospitalisation with COVID-19 in patients with multiple sclerosis relative to patients affected with other autoimmune diseases (inflammatory bowel disease/rheumatoid arthritis), and relative to individuals from the general population. Adjustments were made for age, sex, comorbidity, vaccination, and calendar period. To examine the impact of disease-modifying treatment, the risk of hospitalisation with COVID-19 was estimated in those with disease-modifying treatment versus those without any disease-modifying treatment. RESULTS: We included 7358 patients with multiple sclerosis and a positive COVID-19 PCR test. The adjusted incidence rate ratio (aIRR) for having corticosteroid prescriptions after COVID-19 in patients with multiple sclerosis was 0.93 (95 % CI 0.78 - 1.10), and the aIRR for hospital contacts at neurological departments/admissions with multiple sclerosis as primary diagnosis after COVID-19 infection was 1.10 (95 % 1.00-1.22). Adjusted OR (aOR) for hospitalisation with COVID-19 in the 30 days after a positive COVID-19 PCR test was 3.21 (95 % CI 2.75-3.74) compared to patients with other autoimmune diseases and the aOR was 5.34 (95 % CI 4.65-6.14) for patients with multiple sclerosis compared to all other individuals in the general population with a positive test. We found no increased risk of hospitalisations with COVID-19 in patients with multiple sclerosis using disease-modifying treatment 6 months prior to a positive COVID-19 PCR test compared to patients with multiple sclerosis without disease-modifying treatment (aOR 0.94 (95 % CI 0.69-1.27)). CONCLUSIONS: In this nationwide cohort of patients with multiple sclerosis, COVID-19 did not seem to trigger multiple sclerosis disease activity (based on proxy variables). We found a significantly increased risk of being hospitalised with COVID-19 in the first 30 days after a positive COVID-19 PCR test in patients with multiple sclerosis irrespective of the type of reference population. In patients with multiple sclerosis, the use of disease-modifying treatment did not increase the risk of hospitalisation with COVID-19.

Causes of Patient Nonattendance at Medical Appointments: Protocol for a Mixed Methods Study.

BACKGROUND: Approximately one-third of patient appointments in Danish health care result in failures, leading to patient risk and sizable resource waste. Existing interventions to alleviate no-shows often target the patients. The underlying reason behind these interventions is a view that attendance or nonattendance is solely the patient's problem. However, these interventions often prove to be ineffective and can perpetuate social biases and health inequalities, leaving behind patients who are more vulnerable or disadvantaged (in terms of social, economical, and linguistic factors, etc). A more holistic understanding of no-shows is needed to optimize processes, reduce waste, and support patients who are vulnerable. OBJECTIVE: This study aims to gain a deep and more comprehensive understanding of the causes, mechanisms, and recurring patterns and elements contributing to nonattendance at Danish hospitals in the Region of Southern Denmark. It emphasizes the patient perspective and analyzes the relational and organizational processes surrounding no-shows in health care. In addition, the study aims to identify effective communicative strategies and organizational processes that can support the development and implementation of successful interventions. METHODS: The study uses mixed quantitative-qualitative methods, encompassing 4 analytical projects focusing on nonattendance patterns, patient knowledge and behavior, the management of hospital appointments, and in situ communication. To address the complexity of no-shows in health care, the study incorporates various data sources. The quantitative data sources include the electronic patient records, Danish central registries, Danish National Patient Registry, and Register of Medicinal Product Statistics. Baseline characteristics of patients at different levels are compared using chi-square tests and Kruskal-Wallis tests. The qualitative studies involve observational data, individual semistructured interviews with patients and practitioners, and video recordings of patient consultations. RESULTS: This paper presents the protocol of the study, which was funded by the Novo Nordisk Foundation in July 2022. Recruitment started in February 2023. It is anticipated that the quantitative data analysis will be completed by the end of September 2023, with the qualitative investigation starting in October 2023. The first study findings are anticipated to be available by the end of 2024. CONCLUSIONS: The existing studies of nonattendance in Danish health care are inadequate in addressing relational and organizational factors leading to hospital no-shows. Interventions have had limited effect, highlighting the Danish health care system's failure to accommodate patients who are vulnerable. Effective interventions require a qualitative approach and robust ethnographic data to supplement the description and categorization of no-shows at hospitals. Obtaining comprehensive knowledge about the causes of missed patient appointments will yield practical benefits, enhancing the safety, coherence, and quality of treatment in health care. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): PRR1-10.2196/46227.

Use of Tramadol vs Traditional Opioids and Adverse Outcomes in Patients with Inflammatory Bowel Disease: A Danish Nationwide Cohort Study.

BACKGROUND: Use of traditional opioids (TOs) for pain management has been associated with adverse outcomes among patients with inflammatory bowel diseases (IBDs). It is unknown if similar associations exist for tramadol, a partial opioid agonist and serotonin and norephinephrine reuptake inhibitor. We sought to compare adverse outcomes associated with tramadol vs TOs in an IBD population. METHODS: This nationwide cohort study included adults with IBD diagnosed from 1995 to 2021 in Denmark with subsequent prescriptions for tramadol or TOs. For each analgesic, 2 populations were assessed: initial users (first prescription) and persistent users (first 3 consecutive prescriptions within 365 days). Outcomes included infection, bowel obstruction/ileus, IBD surgery, and mortality within 90 days after the initial use index date (date of first prescription) and within 365 days after the persistent use index date (date of third prescription). Odds ratios adjusted for demographics, comorbidities, and IBD severity were calculated using multivariable logistic regression. RESULTS: We identified 37 377 initial users and 15 237 persistent users of tramadol or TOs. Initial users of tramadol had lower adjusted odds of infection (adjusted odds ratio [OR], 0.80; 95% confidence interval [CI], 0.65-0.99), bowel obstruction/ileus (aOR, 0.74; 95% CI, 0.53-1.03), and mortality (aOR, 0.43; 95% CI, 0.35-0.55), and a higher adjusted odds of IBD-related surgery (aOR, 1.27; 95% CI, 1.02-1.60) vs initial users of TOs. Similar results were found for persistent users. CONCLUSIONS: Tramadol was associated with lower odds of infection, bowel obstruction/ileus, and mortality vs TOs among patients with IBD. These associations may be impacted by residual confounding.

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.

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.

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.

Assisted Reproductive Technology Results Using Donor or Partner Sperm: A Danish Nationwide Register-Based Cohort Study.

This was a nationwide cohort study based on Danish health registers focusing on assisted reproductive technology (ART) treatments in women using donor or partner sperm from 2007 to 2017. Women using donor sperm were subdivided into groups based on relationship status: women with male partners, single women, or women with female partners. The live birth adjusted odds ratios (aORs) after the IUI treatments in women using donor sperm compared with women using partner sperm were 1.48 (95% CI: 1.38-1.59) in women with male partners using donor sperm, 1.20 (95% CI: 1.13-1.28) in single women, and 1.46 (95% CI: 1.32-1.62) in women with female partners. The live birth aORs after IVF treatments in women using donor sperm compared with women using partner sperm were 1.16 (95% CI: 1.02-1.32) in women with male partners using donor sperm, 0.88 (95% CI: 0.80-0.96) in single women, and 1.20 (95% CI: 1.00-1.44), in women with female partners. The use of donor sperm was associated with a higher chance of a live birth after the IUI treatments, but there was no difference after the IVF treatments. Our study invites healthcare professionals to increase their attention toward the different needs and fertility issues of all women attending fertility clinics.