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Importance: Dupilumab, methotrexate (MTX), and cyclosporine A (CsA) are valuable treatment options for pediatric patients with refractory moderate to severe atopic dermatitis (AD). Yet, comparative data on these treatments in pediatric patients are scarce., Objective: To evaluate drug survival of dupilumab, MTX, and CsA, and identify associated predictors in a multicenter daily practice cohort study of pediatric patients with AD., Design, Setting, and Participants: This multicenter daily practice cohort study included patients with AD aged 2 to 17 years treated with dupilumab, MTX, and/or CsA in 5 tertiary centers in the Netherlands between 2013 and 2023. Data were extracted from the prospective BioDay and TREAT Netherlands registries and electronic medical records., Exposures: Dupilumab, MTX, CsA., Main Outcomes and Measures: Drug survival was analyzed using Cox proportional hazard regression models. Univariable and multivariable Cox regression analyses were conducted to identify variables associated with drug discontinuation., Results: A total of 502 treatment episodes in 362 unique patients were included, comprising 192 dupilumab episodes, 94 MTX episodes, and 216 CsA episodes. Overall, the mean (SD) age at treatment initiation was 12.9 (3.8) years, and 272 treatment episodes (54.2%) in female patients. The 1-year, 2-year, and 3-year overall drug survival rates, respectively, were 84.1%, 72.3%, and 62.0% for dupilumab; 60.7%, 39.3%, and 25.3% for MTX; and 43.9%, 21.5%, and 10.4% for CsA. Ineffectiveness was the most frequent reason for drug discontinuation, accounting for 178 episodes (35.5%), mostly in patients treated with CsA, followed by adverse effects in 94 patients (18.7%). Treatment with MTX and treatment with CsA were independently associated with a higher risk for drug discontinuation due to ineffectiveness (hazard ratio [HR], 4.45 [95% CI, 2.38-8.34] and HR, 10.88 [95% CI, 6.23-19.02], respectively) and adverse effects (HR, 4.39 [95% CI, 2.05-9.39] and HR, 3.83 [95% CI, 1.85-7.92], respectively) compared to treatment with dupilumab. Patients aged 12 to 17 years starting systemic treatment were independently associated with a higher risk for drug discontinuation due to ineffectiveness (HR, 1.55 [95% CI, 1.10-2.20]) and adverse effects (HR, 2.39 [95% CI, 1.33-4.30])., Conclusions and Relevance: This multicenter daily practice cohort study demonstrated a superior 1-year, 2-year, and 3-year overall drug survival for dupilumab, followed by MTX, with the lowest rates observed for CsA in pediatric patients with AD. This study also identified characteristics associated with discontinuation. These results provide insight into drug survival resulting from the effectiveness, safety, and tolerability of these systemic treatments in pediatric patients with AD and contribute to the optimization of patient outcomes.

Objective: To assess differences in adverse maternal and neonatal outcomes before and after closure of a secondary obstetric care unit of a community hospital in an urban district., Study Design: Retrospective cohort study using aggregated data from National Perinatal Registry of the Netherlands (PERINED) in the very urban region of Amsterdam, consisting of data of five secondary and two tertiary hospitals. We assessed maternal and neonatal outcomes in singleton hospital births between 24 +0 weeks of gestational age (GA) up to 42 +6 weeks. Data of 78.613 births were stratified in two groups: before closure (years 2012-2015) and after closure (2016-2019)., Results: Perinatal mortality decreased significantly from 0.84 % to 0.63 % (p = 0.0009). The adjusted odds ratio (aOR) of the closure on perinatal mortality was 0.73 (95 % CI 0.62-0.87). Both antepartum death (0.46 % vs 0.36 %, p = 0.02) and early neonatal death (0.38 % vs 0.28 %, p = 0.015) declined after closure of the hospital. The number of preterm births decreased significantly (8.7 % vs 8.1 %, p=<0.007) as well as number of neonates with congenital abnormalities (3.2 % vs2.2 %, p=<0.0001). APGAR < 7 after 5 min increased (2.3 % vs 2.5 %, p = 0.04). There was no significant difference in SGA or NICU admission. Postpartum hemorrhage increased significantly from 7.7 % to 8.2 % (p=<0.003). Perinatal mortality from 32 weeks onwards was not significantly different after closure 0.29 % to 0.27 %., Conclusions: After closure of an obstetric unit in a community hospital in Amsterdam, there was a significant decrease in perinatal, intrapartum and early neonatal mortality in neonates born from 24 +0 onwards. The mortality decrease coincides with a reduction of preterm deliveries. The increasing trend in asphyxia and postpartum hemorrhage is of concern.. Centralization of care and increasing birth volume per hospital may lead to improvement of quality of care. A broad integrated, multidisciplinary maternity healthcare system linked with the social domain can achieve health gains in maternity care for all women., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.)

Competing Interests: Dr Schuttelaar received consultancy fees from Sanofi Genzyme and Regeneron Pharmaceuticals; and is advisory board member for Sanofi, Regeneron, Pfizer, LEO Pharma, Lilly. Authors Zhang, Loman, and Kamphuis have no conflicts of interest to declare.