Search

Background We aimed to explore the epidemiology of inflammatory bowel diseases [IBD] in association with the COVID-19 pandemic in two countries with different lockdown policies. Methods We utilized nationwide IBD cohorts in Israel and Sweden to explore the incidence of IBD during the pandemic compared to 3 years prior [2017–2019]. We examined temporal trends through the presence of inflection points by Joinpoint regression analysis and reported average monthly percentage changes [AMPC]. Results A total of 155 837 patients with IBD were included [Israel, 58 640; Sweden, 97 197]. The annual incidence of IBD was stable until 2019 in both countries but then decreased in Israel (AAPC −16.6% [95% confidence interval, CI, −19.9% to −10.0%]) and remained stable in Sweden (AAPC −3.5% [95% CI −11.6% to 3.7%]). When exploring the monthly incidence during the pandemic, in Israel the rate remained stable until November 2020 (AMPC 2.3% [95% CI −13.4% to 29.9%]) and then decreased sharply (AMPC –6.4% [95% CI –20.8% to 17.0%] until February 2021 and to −20.1% [95% CI –38.9% to –4.7%] from February 2021), while in Sweden, which had a less stringent lockdown policy, it decreased slightly until July 2020 (AMPC −3.3% [95% CI −21.6% to 20.3%]), but increased thereafter (AMPC 13.6% [95% CI –12.6% to 27.0%]). The change of incidence rate in Sweden occurred mainly in elderly-onset patients, the only population with significant restrictions during the pandemic. Conclusion The incidence of IBD decreased during the pandemic in association with lockdowns, more so in Israel, which had more stringent policies. Future studies are needed to determine the long-term effect of the pandemic on IBD. [ABSTRACT FROM AUTHOR]

Background In this nationwide study we aimed to compare the durability of the first initiated biologic in Crohn's disease [CD], stratified by monotherapy and combotherapy. Methods We used data from the epi-IIRN cohort, which includes 98% of the Israeli inflammatory bowel disease population [2005–2020]. Durability was defined as consistent treatment without surgery or added medications [except for combination therapy with thiopurines or methotrexate]. All comparisons were based on stringent propensity-score matching and paired time-to-event analyses. Results A total of 19 264 patients with CD were included, of whom 7452 [39%] received biologics with a median follow-up of 6.8 years (interquartile range [IQR] 3.6–10.7). Time to biologics decreased gradually from 6.7 years [IQR 2.7–10.4] in 2005 to 0.2 years [0.07–0.23] in 2020. The durability of the first biologic after 1 and 3 years was higher with adalimumab monotherapy [88%/61%] than vedolizumab monotherapy [81%/59%; n  = 394 matched patients, p  = 0.04] and similar between infliximab monotherapy and vedolizumab monotherapy [65%/43%; n  = 182 matched patients, p  = 0.1]. Durability was higher in adalimumab monotherapy vs infliximab monotherapy [83%/62% vs 71%/48% at 1/3 years; p  <0.001] and it was similar in adalimumab monotherapy vs infliximab combotherapy [87%/63% vs 80%/58%, respectively; p  = 0.1]. Durability was higher in combotherapy compared with monotherapy for both infliximab [85%/64% vs 67%/43%, respectively; n  = 496 matched pairs, p  <0.001], and adalimumab [93%/76% vs 82%/62%, respectively; n  = 540 matched pairs, p  <0.001]. Conclusion Durability of the first biologic in CD was highest for adalimumab monotherapy. Combotherapy further increased the durability of adalimumab and infliximab. Unless otherwise indicated, our data may support using anti-tumour necrosis factors [TNFs] as first-line biologics in CD, particularly adalimumab if monotherapy is advised. [ABSTRACT FROM AUTHOR]

Objective: To determine the incidence, risk factors, and short-term maternal outcomes of women with pathologically confirmed retained products of conception (RPOC) following vaginal delivery. Methods: Prospective cohort study of women with suspicion of RPOC following vaginal delivery, from March 2018 to April 2019. Women were followed for eight weeks postpartum. Women with complete retained placenta were excluded. Women with pathologically confirmed RPOC were compared to those without. Univariate analysis was conducted (ORs; [95% CI]) and was followed by multivariate analysis (aOR; [95% CI]). Results: During the study period, there were 16,583 vaginal deliveries. A total of 96 women (0.58%) with a suspicion of RPOC were enrolled, of these, 53 women (55%) had pathologically confirmed RPOC. The most significant risk factors for pathologically confirmed RPOC were placental abruption (aOR 5.0 [2.29–11.13]) and Oxytocin augmentation of labor (aOR 1.7 [1.07–2.63]). Pathologically confirmed RPOC were associated with higher rates of prolonged hospitalization (OR 9.2 [2.83–30.05]), postpartum hemorrhage (PPH) (OR 6.6 [3.60–11.98]), hemoglobin drop > 3 g/dl (OR 11.4 [5.49–23.49]), and blood transfusion (OR 8.6 [2.07–38.18]). Women who had exploration of uterine cavity without pathological confirmation of RPOC, still had higher rates of perineal laceration (OR 17.6 [4.93–63.08]), PPH (OR 6.1 [3.05–12.21]), and a hemoglobin drop > 3 g/dl (OR 6.0 [2.13–16.95]). Conclusions: Pathologically confirmed RPOC following vaginal delivery has unique characteristics and is associated with significantly higher rates of PPH and blood transfusions. These findings may assist in the development of better criteria for selecting women for manual exploration and for preventive measures to reduce PPH and complications. [ABSTRACT FROM AUTHOR]

Background It is still of debate whether the advent of biologics has been associated with a change in the natural history of ulcerative colitis [UC]. In this nationwide study we evaluated trends of long-term outcomes in all patients diagnosed with UC in Israel during the biologic era. Methods Data in the epi-IIRN cohort were retrieved from the four Israeli Health Maintenance Organizations covering 98% of the population, and linked to the Ministry of Health prospective registry on surgeries and hospitalizations. Joinpoint Regression and Kaplan–Meier survival analyses were used, reporting annual average percentage change [AAPC] for each outcome. Results A total of 13 231 patients were diagnosed with UC since 2005 (1426 [11%] paediatric-onset, 10 310 [78%] adults, 1495 [11%] elderly) with 93 675 person-years of follow-up. The probabilities of surgery after 1, 3 and 5 years from diagnosis were 1.1, 2.3 and 4.1%, respectively, and the corresponding rates of hospitalizations were 22, 33 and 41%. The overall utilization of biologics in UC increased from 0.1% in 2005 to 9.6% in 2019 [AAPC 22.1%] and they were prescribed earlier during the disease course (median of 5.6 years [interquartile range 2.8–9.1] in 2005–2008 vs 0.8 years [0.4–1.5] in 2015–2018; p < 0.001]. Annual rates of surgeries [AAPC −1.3; p = 0.6] and steroid-dependency [AAPC −1.2; p = 0.3] remained unchanged, while rates of hospitalizations slightly decreased [AAPC −1.2; p < 0.001]. Outcomes were consistently worse in paediatric-onset disease than in adults, despite higher utilization of biologics [28% vs 12%, respectively; p < 0.001]. Conclusion During the biologic era rates of surgeries and steroid-dependency have remained unchanged in patients with UC, while rates of hospitalizations have slightly decreased. [ABSTRACT FROM AUTHOR]

Background Paediatric onset IBD [PIBD] is characterised by a more extensive phenotype than adult-onset IBD and a higher utilisation of immunosuppressive medications; both may be associated with malignancy. We aimed to assess the risk of cancer in a nationwide cohort of PIBD and to explore the risks associated with medical treatments. Methods PIBD patients [<18 years old] were included from the epi-IIRN cohort, covering 98% of the Israeli population from 2005, linked to the national cancer registry. We matched PIBD children to non-IBD children for calculating the cumulative incidence of cancer. Results In all, 3944 PIBD cases were included (2642 [67%] Crohn's disease, 1302 [33%] ulcerative colitis) translating into 23 635 person-years of follow-up, individually matched to 13 005 non-IBD children. By 30 years of age, 14 IBD patients [0.35%, 5.9/10 000 patient-years] were diagnosed with cancer and one [0.03%] with haemophagocytic-lymphohistiocytosis [HLH], compared with 14 [0.11%, 1.9/10 000 patient-years] cases of cancer {relative risk (RR) 2.5 (95% confidence interval [CI] 1.05-6.2); p = 0.04} and no HLH in the comparison-group. There were no cases of hepatosplenic T cell lymphoma, adenocarcinoma, or cholangiocarcinoma. Cancer risk was 15.6 cases/10 000 person-years in those treated with thiopurines alone (RR compared with IBD patients never exposed to either thiopurines or anti-tumuor necrosis factor [TNF] 1.8 [95% CI 0.6-6.1]; p = 0.2), 11.1/10 000 in those treated with anti-TNF alone (RR 1.3 [95% CI 0.3-6.6]; p = 0.5), and 23.1/10 000 treated with combination therapy of anti-TNF and thiopurines (RR 2.8 [95% CI 0.6-13.8]; p = 0.2). Conclusions PIBD confers an increased risk for malignancy compared with non-IBD in children. However, the absolute risk is very low and no differences in risk with specific therapies were apparent in our data. [ABSTRACT FROM AUTHOR]

Background The effectiveness of biologics for improving long-term outcomes in patients with Crohn's disease [CD] is still controversial. In this nationwide study, we aimed to evaluate trends of long-term outcomes in all CD patients in Israel during the biologics era. Methods Trends of outcomes were analysed using data from the four Israeli health maintenance organisations, covering 98% of the population; joinpoint regression models were used to explore changes of these trends over 2005 to 2019. Results A total of 16 936 patients were diagnosed with CD in Israel since 2005 (2932 [17%] paediatric onset, 14 004 [83%] adult onset) with 114 947 person-years of follow-up. The cumulative rate of any CD related surgery was 5%, 9%, 11%, and 14% at 1, 3, 5, and 10 years from diagnosis. The increase in use of biologics was sharp (from 8.9% to 36%; average annual percent change [AAPC], 14.3%), and the time to biologics was shorter in recent years (median time of 4.8 [1.9–8.1] years in those diagnosed in 2005–2008 compared with 0.5 [0.2–1.1] years in those diagnosed in 2015–2018; p  < 0.001). A significant decrease was noted in the hazard of hospitalisations (1.3 [0.1–4.6] years compared with 0.2 [0.02–0.9] years; p  < 0.001), steroid dependency (1.5 [0.2–5.4] years compared with 0.1 [0.02–0.4] years; p  < 0.001), and intestinal surgeries [4.7 [1.6–8.2] years compared with 0.6 [0.2–1.4] years; p  < 0.001), but not of perianal surgery (4.2 [1.1–7.7] years compared with 0.6 [0.2–1.4] years; p  = 0.2). Outcomes were consistently worse in paediatric onset compared with adults. Conclusions The rates of hospitalisations, steroid dependency, and intestinal resections decreased in association with increased use of biologics both in children and in adults, but not the rate of perianal surgeries. [ABSTRACT FROM AUTHOR]

Objectives: The PRASCO trial reported the short-term superiority of an antibiotic cocktail plus intravenous corticosteroids (IVCS) over IVCS alone in children with acute severe colitis (ASC). Here, we report the extension of the PRASCO trial and the long-term outcomes of the antibiotic cocktail in ASC., Methods: This prospective follow-up of the PRASCO trial documented disease outcomes and treatments annually through 5 years. The primary outcome was colectomy, and the secondary outcome was escalation to biologics, analyzed descriptively., Results: A total of 26 children were included (12 receiving IVCS and 14 receiving IVCS + antibiotics), 19% of whom underwent colectomy during the follow-up period. The estimated probability of colectomy at 3, 6, and 12 months from admission were 7.1%, 7.1%, and 21% with IVCS + antibiotics and 0%, 8.3%, and 17% with IVCS. No children required colectomy after the first year of follow-up. The estimated probability of escalating to biologics were 66%, 77%, and 77% after 1, 2, and 3 years with IVCS + antibiotics and 42%, 51%, and 76% with IVCS. Clinical remission was higher in the IVCS + antibiotics group at each timepoint (e.g., 30% vs. 11% at 5-years). Delta of Pediatric Ulcerative Colitis Activity Index (PUCAI) score from baseline to day three of admission predicted future escalation to biologics (area under curves (AUC) 0.84 [95%CI 0.59-1.0])., Conclusion: While adding antibiotics to IVCS may provide better short-term outcomes, the long-term benefits were comparable to IVCS alone. At 5 years, about one-fifth of children had undergone colectomy, and almost four-fifths had escalated to biologics, particularly during the first year after admission., (© 2024 The Author(s). Journal of Pediatric Gastroenterology and Nutrition published by Wiley Periodicals LLC on behalf of European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition.)

Objective: The utilization of biologic drugs in children with inflammatory bowel disease (IBD) surged following the publications of positive results in randomized controlled trials and real-world studies. We aimed to explore the extent of publication bias associated with these findings., Methods: Two reviewers assessed all abstracts evaluating the efficacy or safety of biologics presented at the annual European Society for Pediatric Gastroenterology Hepatology and Nutrition and North American Society for Pediatric Gastroenterology conferences from 2015 to 2019. Abstracts were classified as "positive" or "negative." Time to publication was analyzed using Kaplan-Meier curve and groups were compared using the log-rank test. A Cox proportional model was utilized to determine the likelihood of publication., Results: Out of 209 included abstracts, only 130 (62%) were published as full manuscripts. The median time to publication was 2.8 years (interquartile range = 0-8.2). In the univariate Cox model, the likelihood of publication was four times higher for abstracts reporting positive results (hazard ratio = 4.4 [95% confidence interval, CI = 2.3-8.5]). The probabilities for publication at 1, 3, and 5 years after the conference were 32%, 59%, and 66% for abstracts with significantly positive results in favor of biologic treatment compared to 10%, 22%, and 25% for those with negative results (p < 0.001). In multivariable model, positive results (odds ratio = 6.4 [95% CI = 2.5-16.4]) were significant associated with publication rate., Conclusion: Only 62% of abstracts presented in medical conferences regarding biologics in pediatric IBD are eventually published as full manuscripts, and those reporting positive results were more likely to be published and at an earlier time. Clinicians, guideline groups, and medical authorities dealing with drug approval, need to be aware of potential publication bias of published studies when employing evidence-based management strategies., (© 2024 European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition.)

Background: Data on predictors of complicated ulcerative colitis (UC) course from unselected populations cohorts are scarce. We aimed to utilize a nationwide cohort to explore predictors at diagnosis of disease course in children and adults with UC., Methods: Data of patients diagnosed with UC since 2005 were retrieved from the nationwide epi-IIRN cohort. Complicated disease course was defined as colectomy, steroid-dependency, or the need for biologic drugs. Hierarchical clustering categorized disease severity at diagnosis based on complete blood count, albumin, C-reactive protein and erythrocyte sedimentation rate (ESR), analyzed together., Results: A total of 13 471 patients with UC (1427 [11%] pediatric-onset) including 103 212 person-years of follow-up were included. Complicated disease course was recorded in 2829 (21%) patients: 1052 (7.9%) escalated to biologics, 1357 (10%) experienced steroid-dependency, and 420 (3.1%) underwent colectomy. Probabilities of complicated disease course at 1 and 5 years from diagnosis were higher in pediatric-onset (11% and 32%, respectively) than adult-onset disease (4% and 16%; P < .001). In a Cox multivariate model, complicated course was predicted by induction therapy with steroids (hazard ratio [HR], 1.5; 95% CI, 1.2-2.0), extraintestinal manifestations (HR, 1.3; 95% CI, 1.03-1.5) and the disease severity clusters of blood tests (HR, 1.8; 95% CI, 1.01-3.1), while induction therapy with enemas (HR, 0.6; 95% CI, 0.5-0.7) and older age (HR, 0.99; 95% CI, 0.98-0.99) were associated with noncomplicated course., Conclusion: In this nationwide cohort, the probability of complicated disease course during the first 5 years from diagnosis was 32% in pediatric-onset and 16% in adults with UC and was associated with more severe clusters of routinely collected laboratory tests, younger age at diagnosis, extraintestinal manifestations, and type of induction therapy., (© The Author(s) 2024. Published by Oxford University Press on behalf of Crohn’s & Colitis Foundation. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Background: In this nationwide study, our objective was to compare the durability of first-line biologics in ulcerative colitis (UC), categorized into monotherapy and combotherapy with immunomodulators., Methods: We utilized data from the nationwide epi-IIRN cohort from 2005 to 2020. Durability was defined as consistent treatment without surgery. Comparisons were based on stringent propensity score-matching., Results: We included 15 111 patients with UC, of whom 2322 (15%) received biologics, with a median follow-up of 7.0 years (interquartile range, 3.8-11.0). The durability rate was similar between pediatric-onset and adults after 1 and 5 years from initiation of treatment (72% and 43% vs 71% and 43%, respectively; P = .8). Durability of adalimumab vs infliximab after 1 or 5 years was similar, whether prescribed as monotherapy (65%/46% vs 63%/33%, respectively; n = 182 matched pairs, P = .3) or combotherapy (78%/56% vs 91%/58%, respectively; n = 46 matched pairs, P = .4). Durability of infliximab was higher as combotherapy (85%/50%) vs monotherapy (69%/42%; n = 174 matched pairs, P = .007), while it was similar for adalimumab (80%/52% vs 74%/52%; n = 53 matched pairs, P = .4). The durability rate was similar for vedolizumab monotherapy (77%/56%) compared with adalimumab monotherapy (69%/52%; n = 125 matched patients, P = .1), and infliximab monotherapy (73%/55% vs 62%/44%; n = 78 matched patients, P = .1). However, combotherapy of antitumor necrosis factors (TNFs) had longer durability than vedolizumab (85%/50% vs 75%/43%, respectively; n = 131 matched pairs, P = .02)., Conclusion: After 5 years of treatment, 43% of the patients with UC sustained their first biologic, with similar durability in pediatric and adult-onset onset disease. Anti-TNFs had similar durability to vedolizumab and superior durability when prescribed as combotherapy., (© The Author(s) 2024. Published by Oxford University Press on behalf of Crohn’s & Colitis Foundation. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)