Background Patients with inflammatory bowel diseases (IBD) commonly suffer from pain that requires analgesic therapies such as tramadol and opioids. However, use of traditional opioids (TOs) has been associated with severe infections and mortality in this population. Tramadol, a partial agonist of opioid receptors, has been considered to have less abuse potential compared to TOs. It is unknown if tramadol is associated with fewer IBD-related complications compared to TOs. Methods This was a Danish nationwide cohort study examining adverse outcomes associated with use of tramadol vs TOs in the IBD population. Patients with IBD (ICD-10 codes K50 and K51) diagnosed 1995-2021 in Denmark with subsequent prescriptions for tramadol or TOs were included. For each drug exposure, two populations were defined: initial users (“IUs”; first prescription after IBD diagnosis) and persistent users (“PUs”; first 3 consecutive prescriptions within 365 days after IBD diagnosis). Outcomes included severe (hospital-diagnosed) infection, bowel obstruction or ileus, IBD surgery, and mortality within 90 days after the IU index date (i.e. date of first prescription) and within 365 days after the PU index date (i.e. date of third prescription) (Figure 1). Multivariable logistic regression was performed to determine associations of tramadol vs TOs with outcomes while adjusting for age, sex, Charlson comorbidity index, year of IBD diagnosis, IBD type, IBD duration, and prior immunomodulator use, corticosteroid use, IBD hospitalization, severe infection, bowel obstruction or ileus, and IBD surgery within 6 months before the index date. A sensitivity analysis was performed in which patients with any diagnosis of a malignant neoplasm (ICD-10 codes C00-99) <1 year prior to the first tramadol or TO prescription were excluded. Results We identified 37,377 IUs and 15,237 PUs of tramadol or TOs. Baseline characteristics are presented in Table 1. IUs of tramadol had lower odds of severe infection (adjusted odds ratio [aOR] 0.80, 95% CI 0.65-0.99), bowel obstruction or ileus (aOR 0.74, 95% CI 0.53-1.03), and mortality (aOR 0.43, 95% CI 0.35-0.55), and higher odds of IBD surgery (aOR 1.27, 95% CI 1.02-1.60) vs TOs. PUs of tramadol had lower odds of severe infection (aOR 0.69, 95% CI 0.55-0.86), bowel obstruction or ileus (aOR 0.58, 95% CI 0.39-0.85), and mortality (aOR 0.35, 95% CI 0.28-0.44) but no difference in IBD surgery (aOR 1.13, 95% CI 0.86-1.47) vs TOs (Table 2). Results were unchanged after excluding patients with malignancy (Table 3). Conclusion Use of tramadol was associated with lower odds of severe infection, bowel obstruction or ileus, and mortality vs use of TOs among patients with IBD. Safety comparisons of tramadol to other analgesics are needed.
Study question Are there any differences in the chance of a live birth using donor or partner semen in the different groups of women attending fertility clinics? Summary answer The chance of a live birth improves using donor semen for Intrauterine Insemination (IUI) treatments. No difference is observed for In Vitro Fertilization (IVF) treatments. What is known already Few studies regarding the efficacy of ART treatments using donor semen are available and most of them focus only on IUI treatments. Moreover, they usually do not take into account the different groups of women utilizing them or possible differences with the use of male partner semen. Study design, size, duration Danish nationwide cohort study based on health registers including all ART treatments from 2007 to 2017. The number of treatments in women using donor semen was 31540 for IUI and 7770 for IVF. For women using partner semen the number of treatments was 80949 for IUI and 74425 for IVF. ART treatments in women using donor semen were further subdivided into three groups based on women's relationship status: different-sex couples single women, and same-sex couples. Participants/materials, setting, methods Live birth chance per ART treatment cycle, IUI or IVF, using donor or partner semen has been assessed. In a subanalysis, the difference in a live birth was also evaluated comparing women using partner semen and women using donor semen stratified according to the partner with whom they attend the fertility clinics. The crude and confounders adjusted odds ratio (OR and aOR) were obtained by multilevel logistic regression. Main results and the role of chance A live birth was obtained in 13.9% of IUI treatments in women using donor semen compared to 12.3% in women using partner semen with an aOR of 1.33 (95% CI: 1.27-1.40). More in detail, for different groups of women using donor semen the aOR of live birth after IUI treatments was: aOR 1.48 (95% CI: 1.38-1.59) in women with male partners using donor semen, aOR 1.20 (95% CI: 1.13-1.28) in single women and aOR 1.46 (95% CI: 1.32-1.62) in women with female partners using donor semen. For what concern IVF treatments, 20.7% of treatments in women using donor semen and 25.7% of treatments in women using partner semen resulted in a live birth. The aOR was 0.99 (95% CI: 0.92-1.06). Moreover, for the different groups of women using donor semen compared to women using partner semen, the aOR of live birth after IVF treatments was: aOR 1.16 (95% CI: 1.02-1.32) in women with male partners using donor semen, aOR 0.88 (95% CI: 0.80-0.96) in single women, and aOR 1.20 (95% CI: 1.00-1.44), in women with female partners using donor semen. Limitations, reasons for caution Being an observational study, it is not possible to exclude the presence of unknown confounders or residual confounding which might affect the results. Wider implications of the findings This is one of the few studies assessing the ART success chances using donor or partner semen with attention to the now diverse population groups receiving ART treatments. We hope our results would be useful to healthcare professionals to better advise and help all women and couples attending fertility clinics Trial registration number not applicable
Background The incidence of inflammatory bowel disease (IBD) among children and adolescence is increasing worldwide. Having a chronic condition at a young age may affect educational achievement and later employment and self-support. The study aims to examine the impact of being diagnosed with IBD before 18 years of age on achieving an upper secondary education before 25 years of age. Methods Using the Danish National Patient Register (1980-2018) all patients (born 1970-1994) diagnosed with IBD at a young age (<18 years) were identified. The IBD-patients were matched on age and sex with 10 references without IBD at the index date (date of diagnosis of IBD). The outcome was achieving an upper secondary education using data from Danish Education Registers. The association between IBD diagnosis and achieving an upper secondary education was analyzed using Cox regression with robust variance estimation adjusting for parents’ highest educational level. Furthermore, stratified analyses were performed on parental socioeconomic status (education and income). Results We identified 3,178 patients with IBD: Crohn’s disease (CD) n = 1,344, Ulcerative colitis (UC) n = 1,834. Reference n = 28,220. The median age at diagnosis was 15.3 years (IQR: [13.0;16.9]). At the age of 25 74.0% (CI: 71.6-76.4) for CD, 75.8% (CI: 73.8-77.8) for UC, and 69.7% (CI: 69.2-70.3) for references had achieved an upper secondary education. The adjusted Hazard ratio (HR) of achieving an upper secondary education was 1.05 (CI: 1.00 -1.11) for CD and 1.09 (CI: 1.04 -1.15) for UC. When stratifying the IBD-patient with the lowest socioeconomic status performed better than their peers. Conclusions Being diagnosed with IBD before 18 years of age did not reduce the chance of achieving an upper secondary education. Patients with low socioeconomic status performed better than their peers, however the study gives no explanation of this. Key messages • Children diagnosed with IBD before 18 years of age had at least the same chance of achieving an upper secondary education compared to references. • IBD patients with low social economic status performed better than their peers.
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