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The unconventional superconductor Sr2RuO4 has long served as a benchmark for theories of correlated-electron materials. The determination of the superconducting pairing mechanism requires detailed experimental information on collective bosonic excitations as potential mediators of Cooper pairing. We have used Ru L3-edge resonant inelastic x-ray scattering to obtain comprehensive maps of the electronic excitations of Sr2RuO4 over the entire Brillouin zone. We observe multiple branches of dispersive spin and orbital excitations associated with distinctly different energy scales. The spin and orbital dynamical response functions calculated within the dynamical mean-field theory are in excellent agreement with the experimental data. Our results highlight the Hund metal nature of Sr2RuO4 and provide key information for the understanding of its unconventional superconductivity. The authors present resonant inelastic x-ray scattering measurements of Sr2RuO4 in the normal Fermi-liquid state. They find that spin excitations are confined below 200 meV, while orbital fluctuations appear only at higher energies. This separation of energy scales is a hallmark of Hund's-rule-induced electron correlations. [ABSTRACT FROM AUTHOR]

Background: Exposure to isotretinoin during pregnancy must be avoided due to its teratogenicity, but real-world data on its use are scarce. We aimed to describe (i) isotretinoin use in women of childbearing age in Germany; (ii) the occurrence of isotretinoin-exposed pregnancies; and (iii) malformations among children exposed in utero., Methods and Findings: Using observational data from the German Pharmacoepidemiological Research Database (GePaRD, claims data from approximately 20% of the German population), we conducted annual cross-sectional analyses to determine age-standardized prevalence of isotretinoin use between 2004 and 2019 among girls and women aged 13 to 49 years. In cohort analyses, we estimated the number of exposed pregnancies by assessing whether there was prescription supply overlapping the beginning of pregnancy (estimated supply was varied in sensitivity analyses) or a dispensation within the first 8 weeks of pregnancy. Data of live-born children classified as exposed in a critical period according to these criteria were reviewed to assess the presence of congenital malformations. The age-standardized prevalence of isotretinoin use per 1,000 girls and women increased from 1.20 (95% confidence interval [CI]: 1.16, 1.24) in 2004 to 1.96 (95% CI: 1.92, 2.01) in 2019. In the base case analysis, we identified 178 pregnancies exposed to isotretinoin, with the number per year doubling during the study period, and at least 45% of exposed pregnancies ended in an induced abortion. In sensitivity analyses, the number of exposed pregnancies ranged between 172 and 375. Among live-born children, 6 had major congenital malformations. The main limitation of this study was the lack of information on the prescribed dose, i.e., the supply had to be estimated based on the dispensed amount of isotretinoin., Conclusions: Isotretinoin use among girls and women of childbearing age increased in Germany between 2004 and 2019, and there was a considerable number of pregnancies likely exposed to isotretinoin in a critical period. This highlights the importance of monitoring compliance with the existing risk minimization measures for isotretinoin in Germany., Competing Interests: The authors have declared that no competing interests exist. JR, NW, KP, BK, and UH are working at an independent, non-profit research institute, the Leibniz Institute for Prevention Research and Epidemiology – BIPS. Unrelated to this study, BIPS occasionally conducts studies financed by the pharmaceutical industry. These are post-authorization safety studies (PASS) requested by health authorities. The design and conduct of these studies as well as the interpretation and publication are not influenced by the pharmaceutical industry. The study presented was not funded by the pharmaceutical industry., (Copyright: © 2024 Reinold et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background and Objective: Acitretin has long-lasting teratogenic properties. Therefore, pregnancies must be avoided during and within 3 years after acitretin treatment. We aimed to describe (i) acitretin use in women of childbearing age in Germany, (ii) the occurrence of acitretin-exposed pregnancies, and (iii) malformations among children exposed in utero., Methods: Using 2004-2019 data from the German Pharmacoepidemiological Research Database (GePaRD-claims data from ~ 20% of the German population), we determined annual age-standardized prevalence of acitretin use among girls and women aged 13-49 years. In longitudinal analyses, we estimated the number of exposed pregnancies by assessing whether the exposure window assigned to the last dispensation before pregnancy (days covered by dispensation plus 3 years) overlapped the onset of pregnancy or whether there was a dispensation in the first eight weeks of pregnancy. Data of live-born children with in utero exposure to acitretin were reviewed to assess the presence of congenital malformations., Results: The age-standardized prevalence of acitretin use per 1000 girls and women was 0.04 in 2019. We identified 35 acitretin-exposed pregnancies; 94.3% of these pregnancies were classified as exposed because they occurred within 3 years after stopping acitretin treatment. Among 18 live-born children linked to their mother, four children (22.2%) had congenital malformations (three children with a major malformation)., Conclusions: We observed 35 acitretin-exposed pregnancies mainly because treatment ended too late before pregnancy. Approximately one in five children born from these pregnancies had malformations, highlighting the importance of drawing more attention to the long-lasting teratogenicity of this drug., (© 2023. The Author(s).)

Background and Objective: Methotrexate should be withdrawn before pregnancy because of its teratogenic potential. We aimed to describe the use of methotrexate in women of childbearing age in Germany and the occurrence and outcomes of pregnancies exposed to methotrexate., Methods: Using the German Pharmacoepidemiological Research Database (GePaRD, covering ~ 20% of the German population), we determined the age-specific and age-standardized prevalence of methotrexate use for each year between 2004 and 2019 among women aged 13-49 years (cross-sectional analyses). In a cohort analysis, we assessed the number and outcomes of pregnancies exposed to methotrexate in the critical time window. Exposure was defined as a dispensation overlapping with the onset of pregnancy or a dispensation in the first 8 weeks of pregnancy. For children born from exposed pregnancies, the mother's and children's data were linked and the occurrence of malformations was assessed by reviewing all available data of these children., Results: The age-standardized prevalence of methotrexate use per 1000 females increased from 1.5 in 2004 to 2.3 in 2019, i.e., by 52%. Overall, we identified 184 pregnancies exposed to methotrexate. Of these, 53% ended in a live birth (21% preterm) and 11% in an induced abortion. Among 81 live-born children linked to their mothers, five children (6%) had relevant malformations including congenital heart defects and musculoskeletal malformations., Conclusions: In Germany, the use of methotrexate in women of childbearing age has substantially increased since 2004. Despite the known teratogenic effect, there was a considerable number of exposed pregnancies.  Also, malformations likely associated with methotrexate and thus avoidable were observed., (© 2022. The Author(s).)

Background: Authorizations of fingolimod, teriflunomide and cladribine were accompanied by risk minimization measures concerning their teratogenic potential. Real-world data on their use are scarce. We aimed to assess trends in the use of fingolimod, teriflunomide and cladribine among women of childbearing age, estimate the number of pregnancies occurring under treatment and explore the occurrence of malformations in newborns exposed during early pregnancy in Germany., Methods: Using the German Pharmacoepidemiological Research Database (GePaRD, claims data from ∼20% of the German population), we determined annual age-standardized prevalences of fingolimod, teriflunomide and cladribine use from their authorization until 2019 among women aged 13-49 years (cross-sectional analyses). In longitudinal analyses, we estimated the number of exposed pregnancies by assessing whether there was an overlap between the exposure windows assigned to dispensations and the onset of pregnancy or a dispensation in the first eight weeks of pregnancy. For live births, a mother-baby linkage was performed. All available data of children with in-utero exposure and malformation codes in the first year of life were reviewed to verify the occurrence of congenital malformations., Results: For fingolimod, the age-standardized prevalence of use per 1,000 females increased from 0.14 in 2011 to 0.46 in 2019; for teriflunomide, from 0.06 in 2013 to 0.28 in 2019; for cladribine, from 0.01 in 2017 to 0.07 in 2019. The proportion of users aged ≤40 years was 60% for fingolimod, 45% for teriflunomide and 65% for cladribine. We identified 136 pregnancies exposed to fingolimod, 50 to teriflunomide and one to cladribine. For fingolimod and teriflunomide, respectively, 72% and 62% of exposed pregnancies ended in a live birth. Mother-newborn linkage was successful in 64 (fingolimod) and 20 (teriflunomide) live-born children. Among these, there were six with relevant malformations (mainly heart defects) for fingolimod and two for teriflunomide., Conclusion: Use of fingolimod, teriflunomide and cladribine among women of childbearing age has substantially increased in Germany. A high proportion of users was in age groups in which pregnancies typically occur. Despite risk minimization measures, early pregnancy exposure to these drugs was observed., Competing Interests: Declaration of Competing Interest The authors are working at an independent, non-profit research institute, the Leibniz Institute for Prevention Research and Epidemiology – BIPS. Unrelated to this study, BIPS occasionally conducts studies financed by the pharmaceutical industry. Almost exclusively, these are post-authorization safety studies (PASS) requested by health authorities. The design and conduct of these studies as well as the interpretation and publication are not influenced by the pharmaceutical industry. The study presented was not funded by the pharmaceutical industry and was performed in line with the ENCePP Code of Conduct., (Copyright © 2022. Published by Elsevier B.V.)

Purpose: To characterize pregnancies among women with epilepsy who have filled a prescription for valproate at any time before or during pregnancy and to assess other antiepileptic drug (AED) prescriptions., Methods: Based on health claims data (German Pharmacoepidemiological Research Database - GePaRD; covering ~20% of the population), we selected pregnancies beginning between 2014 and 2016 in women with at least three years of observation period before pregnancy and with at least one epilepsy diagnosis code in the year before pregnancy. Among those, we selected pregnancies with at least one valproate dispensation any time before or during pregnancy. We further described these pregnancies regarding patterns in the dispensation of valproate and other AED among the women from their first day in the database until the end of the pregnancy., Results: Among 2068 pregnancies fulfilling the inclusion criteria, we identified 454 pregnancies (89% ending in live births and 8% in induced abortions) in 430 women with at least one valproate dispensation before or during pregnancy. In 357 of these pregnancies (79%), valproate was only dispensed before pregnancy, while 97 pregnancies (21%) had a valproate dispensation during pregnancy and of these, 77% (N = 75) during the first trimester. The proportion with a valproate dispensation during pregnancy declined from 2014 (25%) to 2016 (19%), also concerning exposure during the first trimester (2014: 20%, 2015: 17%, 2016: 12%), while the proportion ending in an induced abortion was increasing (2014: 5%, 2015: 8%, 2016: 13%). In 48% of exposed pregnancies (N = 36), there was no other AED dispensed during the entire observation time before pregnancy. This proportion was lower for pregnancies beginning in 2016 (33%) than for those beginning in 2014 and 2015 (53% and 50%, respectively)., Conclusion: In most women with epilepsy using valproate before or during pregnancy, valproate was dispensed only well before pregnancy beginning. The proportion exposed to valproate during the first trimester declined between 2014 and 2016, but the low proportion treated with alternative AED before valproate treatment suggests there is still room for improvement., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Little is known about the utilization of St. John's wort (Hypericum perforatum L.) during pregnancy. In Germany, certain preparations of St. John's wort can be reimbursed by statutory health insurances, facilitating to investigate exposure to St. John's wort based on claims data. We therefore aimed to characterize pregnancies exposed to St. John's wort and to explore potential malformations in the babies. Using claims data from the German Pharmacoepidemiological Research Database (GePaRD), pregnancies exposed to St. John's wort during at least one trimester between 2006 and 2016 and the corresponding babies were identified. Exposure was identified via outpatient dispensations. Pregnancies were characterized regarding timing of exposure, use of other antidepressants, pregnancy outcomes and the occurrence of major malformations in the babies (not considering codes for musculoskeletal and other malformations due to low data quality in this regard). Out of 496 pregnancies with a dispensation of St. John's wort during pregnancy, 420 (85 %) had a dispensation during the first trimester. There was a dispensation of other antidepressants before pregnancy in 21 % (during pregnancy: 12 %). Eleven percent of pregnancies ended in non-live births. In 312 babies linked to 305 pregnancies, major malformations were coded in 18 babies (5.8 %), of which 17 were exposed in the first trimester. The crude relative risk of major malformations for babies exposed during the first vs. the second or third trimester only was 3.56 (0.48-26.17). Our results suggest that only in a minority of pregnancies, St. John's wort is used as an alternative to other antidepressants. Even though the relatively high rates of non-live births and major malformations after exposure to St. John's wort during the first trimester need to be interpreted with caution, the findings are striking and generate hypotheses that merit further investigation., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: Estimating the beginning of pregnancy is crucial when studying drug safety in pregnancy, but important information in this regard, such as the last menstrual period (LMP), is generally not recorded in claims databases. The beginning of pregnancy is therefore usually estimated by subtracting a median length of pregnancy from the date of birth. Due to the variability in pregnancy lengths, this might result in non-negligible errors. German claims data may offer the possibility to estimate the beginning of pregnancy more precisely based on the expected delivery date (EDD) which can be coded once or more often during a pregnancy. Purpose: To estimate the beginning of pregnancy in German claims data focusing on the potential of the expected delivery date (EDD). Methods: We included data of all pregnancies in women aged 12-50 years ending in a live birth between 2006 and 2015 identified in the German Pharmacoepidemiological Research Database (GePaRD). We assessed the number of coded EDDs per pregnancy and the concordance if ≥ 2 EDDs were coded. We estimated the beginning of pregnancy by subtracting 280 days from the EDD or the most frequent EDD (in case of discordant EDDs). To examine plausibility, we determined the distribution of pregnancy lengths and assessed whether the gestational age at which prenatal examinations were coded was plausible. For pregnancies without EDD, the beginning was estimated by subtracting the respective observed median lengths of pregnancy for preterm births, term births, and births after due date from the actual dates of birth. Results: In 82.4% of pregnancies, at least one EDD was available (thereof 6.1% with only one EDD and 80.9% with ≥ 2 EDDs that were all concordant). The maximal difference between discordant EDDs was in median 5 days (interquartile range: 3-7 days). Based on the EDD, the median length of pregnancy was 276 days for term births and in 84.7% of pregnancies the second antibody screening test was performed in the recommended interval ± 2 weeks. In pregnancies without EDD the respective proportion was 84.9%. Conclusions: By using the EDD, the beginning of pregnancy can plausibly be estimated in German claims data., (Copyright © 2020 Schink, Wentzell, Dathe, Onken and Haug.)

"Strange metals" with resistivity depending linearly on temperature T down to low T have been a long-standing puzzle in condensed matter physics. Here, we consider a lattice model of itinerant spin-[Formula: see text] fermions interacting via onsite Hubbard interaction and random infinite-ranged spin-spin interaction. We show that the quantum critical point associated with the melting of the spin-glass phase by charge fluctuations displays non-Fermi liquid behavior, with local spin dynamics identical to that of the Sachdev-Ye-Kitaev family of models. This extends the quantum spin liquid dynamics previously established in the large-M limit of [Formula: see text] symmetric models to models with physical [Formula: see text] spin-[Formula: see text] electrons. Remarkably, the quantum critical regime also features a Planckian linear-T resistivity associated with a T-linear scattering rate and a frequency dependence of the electronic self-energy consistent with the marginal Fermi liquid phenomenology., Competing Interests: The authors declare no competing interest., (Copyright © 2020 the Author(s). Published by PNAS.)

Purpose: For studying drug utilization and safety in pregnancy based on administrative health care data, the reliable identification and classification of pregnancy outcomes in the data is essential. We aimed to optimize an existing algorithm for the identification and classification of pregnancy outcomes in the German Pharmacoepidemiological Research Database (GePaRD) with a particular focus on births., Methods: We reconsidered all codes used by the original algorithm and applied it to data of GePaRD from 2006 to 2014. Longitudinal records of pregnancies were used to identify targets for enhancing the algorithm's specificity. We checked the plausibility of the results, eg, regarding the age distribution of persons with pregnancy outcomes. Based on 20 longitudinal records of pregnancies, we compared the outcome classification by clinical experts with the results of the modified algorithm., Results: Our algorithm identified 1 235 261 pregnancy outcomes in the database, with the majority (94%) being live births, classified as preterm (10%), term (78%), and (12%) births after the expected delivery date. The median age of pregnant women was 32 years (Q1 28; Q3 35). Implausible sequence of outcomes (for example, an induced abortion within a pregnancy categorized as ending in a live birth) were rare (0.03%). The case profile review by clinical experts resulted in the same outcome type and date as the algorithm in 95%., Conclusions: Our algorithm led to plausible results regarding the identification and classification of pregnancy outcomes. It will be an important foundation for studies on drug utilization and drug safety during pregnancy based on GePaRD., (© 2018 John Wiley & Sons, Ltd.)

Background: Measures to raise awareness of the teratogenic potential of valproate and restrict its use in girls/women of childbearing age have been intensified. For Germany, the impact of these measures on valproate prescription rates remains unknown., Objectives: Trends in prescribing valproate, the underlying treatment indication, and the specialty of the prescribing physician are analyzed., Materials and Methods: With claims data from several statutory health insurance providers from 2004 to 2016 (approximately 3.5 million insured persons per year) considering treatment indication and medical specialties of prescribing physicians, we assessed the rate of girls/women (12 to 50 years) with at least one valproate dispensation per year., Results: The age-standardized rate of girls/women with at least one valproate dispensation declined by 28% between 2004 and 2016 (2.91/1000 vs. 2.09/1000). For 2015, the indications were epilepsy (66.9%), bipolar disorder (13.6%), migraine/headache (5.6%), schizoaffective disorder (4.3%), and other mental disorders (8.9%). Among epilepsy patients, the proportion treated with valproate declined from 26.2 to 16.8%, but changed little in patients with bipolar disorder (9.3% vs. 8.0%). A total of 46.3% of valproate dispensations were issued by neurologists or psychiatrists and 29.6% by general practitioners, internal medicine specialists, or family doctors., Conclusions: Based on German claims data, a decline of valproate dispensations was shown for epilepsy patients of childbearing age, while the proportion in other indications has hardly changed since 2004.

The Patient Safety Culture Improvement Tool (PSCIT) was developed to assist healthcare organizations in identifying practical actions to improve their culture. This article describes the development process of the PSCIT and provides a guide to using the PSCIT. The tool is based on a safety culture maturity model, which describes five stages of cultural evolution, from pathological to generative. The PSCIT consists of nine elements that cover five patient safety culture dimensions, namely, leadership, risk analysis, workload management, sharing and learning and resource management. Each element describes the systems in place at each level of maturity, enabling organizations to identify their current level of maturity and actions to move to the next level. The PSCIT should be used with caution as there is currently a lack of reliability and validity data.