The European Clozapine Task Force is a group of psychiatrists and pharmacologists practicing in 18 countries under European Medicines Agency (EMA) regulation, who are deeply concerned about the underuse of clozapine in European countries. Although clozapine is the most effective antipsychotic for people with treatment-resistant schizophrenia, a large proportion of them do not have access to this treatment. Concerns about clozapine-induced agranulocytosis and stringent blood monitoring rules are major barriers to clozapine prescribing and use. There is a growing body of evidence that the incidence of clozapine-induced agranulocytosis is very low after the first year of treatment. Maintaining lifelong monthly blood monitoring after this period contributes to unjustified discontinuation of clozapine. We leverage recent and replicated evidence on the long-term safety of clozapine to call for the revision and updating of the EMA’s blood monitoring rules, thus aiming to overcome this major barrier to clozapine prescribing and use. We believe the time has come for relaxing the rules without increasing the risks for people using clozapine in Europe.

Interpersonal psychotherapy (IPT) and antidepressant medications are both first-line interventions for adult depression, but their relative efficacy in the long term and on outcome measures other than depressive symptomatology is unknown. Individual participant data (IPD) meta-analyses can provide more precise effect estimates than conventional meta-analyses. This IPD meta-analysis compared the efficacy of IPT and antidepressants on various outcomes at post-treatment and follow-up (PROSPERO: CRD42020219891). A systematic literature search conducted May 1st, 2023 identified randomized trials comparing IPT and antidepressants in acute-phase treatment of adults with depression. Anonymized IPD were requested and analyzed using mixed-effects models. The prespecified primary outcome was post-treatment depression symptom severity. Secondary outcomes were all post-treatment and follow-up measures assessed in at least two studies. IPD were obtained from 9 of 15 studies identified (N = 1536/1948, 78.9%). No significant comparative treatment effects were found on post-treatment measures of depression (d = 0.088, p = 0.103, N = 1530) and social functioning (d = 0.026, p = 0.624, N = 1213). In smaller samples, antidepressants performed slightly better than IPT on post-treatment measures of general psychopathology (d = 0.276, p = 0.023, N = 307) and dysfunctional attitudes (d = 0.249, p = 0.029, N = 231), but not on any other secondary outcomes, nor at follow-up. This IPD meta-analysis is the first to examine the acute and longer-term efficacy of IPT v. antidepressants on a broad range of outcomes. Depression treatment trials should routinely include multiple outcome measures and follow-up assessments.

Relatively little is known regarding factors that may mitigate the strength of the associations between forms of aggressive behavior and peer victimization. The goal of the current study was to investigate prosocial behavior as a moderator of these links over a 2-year period during middle childhood. Participants included 410 third-grade students (53% boys) and their homeroom teachers. Results indicated that prosocial behavior was associated with lower initial levels of victimization, whereas relational aggression was associated with higher initial levels of victimization. Physical aggression predicted more stable patterns of victimization over time, and prosocial behavior moderated the prospective link from relational aggression to peer victimization; specifically, relational aggression predicted decreases in victimization at higher levels of prosocial behavior and more stable patterns over time when levels of prosocial behavior were low. Further, gender differences were observed in the moderating effect of prosocial behavior on the prospective link from physical aggression to peer victimization, such that it served as a risk factor for boys and a protective factor for girls.

This systematic review and meta-analysis were conducted to evaluate the prevalence of cardiac manifestations associated with multisystem inflammatory syndrome in children worldwide. We conducted electronic searches in Ovid MEDLINE, Ovid EMBASE, and the World Health Organization COVID-19 Literature Database from the inception of the SARS-CoV-2 pandemic to 1 January, 2022. Three authors independently screened the abstracts to determine eligibility, assessed methodology in the full texts, and extracted the data.

We identified 2848 citations; 94 studies (14,932 patients) were included. The prevalence of vasopressors was 48.2% (95% CI 45.1%, 51.3%), left ventricular systolic dysfunction occurred in 37.2% (95% CI 34.1%, 40.3%), myocarditis in 34.1% (95% CI 30.5%, 37.8%), electrocardiographic dysrhythmias and abnormalities detected in 23.1% (95% CI 18.8%, 27.6%), coronary abnormalities identified in 18% (95% CI 16%, 20%), extracorporeal membrane oxygenation deployed in 2.2% (95% CI 1.7%, 2.8%), and mortality rate of 2.2% (95% CI 1.7%, 2.7%). A sensitivity analysis was performed after removing eleven studies with high bias, and the adjusted prevalence was not different than the original evaluation.

In this meta-analysis of the largest cohort of multisystem inflammatory syndrome in children patients to date, we established the most accurate prevalence of the most common cardiac manifestations. Providers will subsequently have more precise data to anticipate patient outcomes and approach discussions concerning the frequency of monitoring outside the acute hospital period.

Beer was a staple of early modern diets across northern Europe and the Atlantic World. While its profound social, economic, and cultural significance is well established, little is known about the nature and quality of the drink itself, particularly its nutritional characteristics. Until now, attempts to estimate calorie and alcohol content have been monodisciplinary in approach, involving either theoretical calculations based on grain content, or a rough approximation with modern equivalents. Using sixteenth-century Ireland as a case-study, this article describes an interdisciplinary approach to the problem of early modern beer. Exploiting a rich seam of unpublished archival material, the project recreates an early modern beer, using the most appropriate ingredients, equipment, and processes possible. Scientific analysis of the finished drink offers new perspectives on beer as a dietary staple. The project is a model for integrating practical or experimental approaches into mainstream historical study, and the practice of radical interdisciplinarity. It represents the most comprehensive effort to recreate an historic beer in any context to date, bringing together historians, experimental archaeologists, agronomists, microbiologists, brewing scientists, craftworkers, farmers, and maltsters to tackle problematic questions about the past.

This article is a clinical guide which discusses the “state-of-the-art” usage of the classic monoamine oxidase inhibitor (MAOI) antidepressants (phenelzine, tranylcypromine, and isocarboxazid) in modern psychiatric practice. The guide is for all clinicians, including those who may not be experienced MAOI prescribers. It discusses indications, drug-drug interactions, side-effect management, and the safety of various augmentation strategies. There is a clear and broad consensus (more than 70 international expert endorsers), based on 6 decades of experience, for the recommendations herein exposited. They are based on empirical evidence and expert opinion—this guide is presented as a new specialist-consensus standard. The guide provides practical clinical advice, and is the basis for the rational use of these drugs, particularly because it improves and updates knowledge, and corrects the various misconceptions that have hitherto been prominent in the literature, partly due to insufficient knowledge of pharmacology. The guide suggests that MAOIs should always be considered in cases of treatment-resistant depression (including those melancholic in nature), and prior to electroconvulsive therapy—while taking into account of patient preference. In selected cases, they may be considered earlier in the treatment algorithm than has previously been customary, and should not be regarded as drugs of last resort; they may prove decisively effective when many other treatments have failed. The guide clarifies key points on the concomitant use of incorrectly proscribed drugs such as methylphenidate and some tricyclic antidepressants. It also illustrates the straightforward “bridging” methods that may be used to transition simply and safely from other antidepressants to MAOIs.

We previously reported a putative detection of a radio galaxy at $z=10.15$ , selected from the GaLactic and Extragalactic All-sky Murchison Widefield Array (GLEAM) survey. The redshift of this source, GLEAM J0917–0012, was based on three weakly detected molecular emission lines observed with the Atacama Large Millimetre Array (ALMA). In order to confirm this result, we conducted deep spectroscopic follow-up observations with ALMA and the Karl Jansky Very Large Array (VLA). The ALMA observations targeted the same CO lines previously reported in Band 3 (84–115 GHz) and the VLA targeted the CO(4-3) and [CI(1-0)] lines for an independent confirmation in Q-band (41 and 44 GHz). Neither observation detected any emission lines, removing support for our original interpretation. Adding publicly available optical data from the Hyper Suprime-Cam survey, Widefield Infrared Survey Explorer (WISE), and Herschel Space Observatory in the infrared, as well as $<$ 10 GHz polarisation and 162 MHz inter-planetary scintillation observations, we model the physical and observational characteristics of GLEAM J0917–0012 as a function of redshift. Comparing these predictions and observational relations to the data, we are able to constrain its nature and distance. We argue that if GLEAM J0917–0012 is at $z<3,$ then it has an extremely unusual nature, and that the more likely solution is that the source lies above $z=7$ .

The record of Middle Ordovician (Oretanian, ca. Darriwilian 2) hyolithids from the Ossa Morena Zone of the Iberian Massif in southwestern Spain is increased with the recognition of Robardetlites sevillanus n. gen. n. sp., Andalucilites parvulus n. gen. n. sp., Pauxillites desolatus n. sp., Leolites malinkyi Marek and Gutiérrez-Marco n. sp., and Cavernolites sp. in that region. Andalucilites n. gen. and Robardetlites n. gen. are endemic whereas the other genera are known from coeval strata in the Barrandian region in central Europe, France, and Morocco, giving this assemblage a decidedly “Mediterranean province” character. The discovery of Pauxillites, Leolites, and Cavernolites in Iberia extends their geographic ranges to that region, and Leolites from this area extends its stratigraphic range downward, making its occurrence in Iberia the oldest known for that genus.

UUID: http://zoobank.org/f5b29223-6dac-4c7e-8851-551e634da667

ABSTRACT IMPACT: This project demonstrates that addressing low-value care, which has the potential to cause patient harm, relies on novel data tools and collaboration between health system and research stakeholders. OBJECTIVES/GOALS: Reducing low-value care, or patient care that offers no net benefit in specific clinical scenarios, is an important approach to improving value as it can simultaneously lower health care spending and improve quality. We describe an initiative to identify such care in a large statewide employer. METHODS/STUDY POPULATION: Claims data for self-funded University of California (UC) Preferred Provider Organization (PPO) plan members during 2019 were abstracted from the University of California Health (UCH) Clinical Data Warehouse, a unique central database that includes electronic medical record data from >5 million patients across UC medical campuses and all claims from UC self-funded health plans. UCH spans six academic health systems across California. The Milliman MedInsight Health Waste Calculator, a proprietary algorithm-based software tool, was used to identify low-value care and estimate associated spending. The HWC measures 48 low-value services using recommendations from the Choosing Wisely Campaign, the US Preventive Services Task Force, and other clinical specialty guidelines. RESULTS/ANTICIPATED RESULTS: Of 43,882 members of the UC PPO, 11,174 (25.4%) received at least one low-value service. The HWC identified 50,103 eligible services and classified 35% as low-value. Total spending on low-value services ranged between $2,209,516 and $5,089,866, based on a more or less conservative estimate. Across the five sites, the proportion of low-value services ranged from 31% to 39%. Five services comprised 65% of costs from low-value care: annual EKGs, preoperative baseline labs for low-risk surgeries, vitamin D deficiency screening, imaging for eye disease, and headache imaging. The top five services by order frequency were annual EKGs, vitamin D tests, preoperative labs, antibiotics for upper respiratory infections, and imaging for eye disease. DISCUSSION/SIGNIFICANCE OF FINDINGS: Low-value care is prevalent and costly within a large statewide employer. Collaborative multidisciplinary partnerships between employers, health systems, informatics, and researchers can leverage existing data to identify opportunities for improving the value of care for covered populations.

Crary Ice Rise formed after the Ross Ice Shelf re-grounded ~1 kyr BP. We present new ice-penetrating radar data from two systems operating at center frequencies of 7 and 750 MHz that confirm the ice rise is composed of a former ice shelf buried by subsequent accumulation. Stacks of englacial diffraction hyperbolas are present almost everywhere across the central ice rise and extend up to ~350 m above the bed. In many cases, bed reflections beneath the diffraction hyperbolas are obscured for distances up to 1 km. Waveform modeling indicates that the diffraction hyperbolas are likely caused by marine ice deposits in former basal crevasses and rifts. The in-filling of rifts and basal crevasses may have strengthened the connection between the ice rise and the surrounding ice shelf, which could have influenced local and regional ice dynamics. Three internal reflection horizons mark the upper limit of disturbed ice and diffraction hyperbolas in different sections of the ice rise, indicating at least three stages of flow stabilization across the ice rise. A surface lineation visible in MODIS imagery corresponds spatially to deepening and strong deformation of these layers, consistent with the characteristics of former grounding lines observed elsewhere in Antarctica.