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Esketamine nasal spray (ESK) is approved in combination with an oral antidepressant (OAD) for the treatment of adults with treatment-resistant depression (TRD); however, direct comparisons with atypical antipsychotics for TRD are limited. This secondary analysis of the ESCAPE-TRD study compared rates of remission and response, and improvements in depressive symptoms over time, between ESK and quetiapine extended-release (XR) in patients with TRD treated in accordance with US prescribing information (USPI).
Methods
ESCAPE-TRD (NCT04338321) was a randomized, open-label, rater-blinded phase 3b trial investigating ESK versus quetiapine XR for acute and maintenance treatment of patients with TRD. This secondary analysis included patients aged 18–64 years who were treated/dosed according to USPI. The primary endpoint was remission, defined as Montgomery–Åsberg Depression Rating Scale (MADRS) total score ≤ 10. Treatment-emergent adverse events (TEAEs) leading to discontinuation were summarized descriptively.
Results
Among 636 patients in this secondary analysis (ESK, n = 316; quetiapine XR, n = 320), significantly more ESK-treated patients achieved remission starting at week 8 (28.3% versus 18.6%; P = 0.005) through week 32 (55.7% versus 36.3%; P < 0.001), compared with quetiapine XR–treated patients. There were clinically and statistically significant improvements in MADRS scores with ESK versus quetiapine XR at each visit from day 8 onwards. Fewer patients discontinued treatment because of TEAEs with ESK (4.5%) versus quetiapine XR (10.1%).
Conclusions
Consistent with the primary analysis, this secondary analysis demonstrated that ESK improves short- and long-term outcomes compared with quetiapine XR in patients with TRD treated according to USPI.
The coronavirus disease 2019 (COVID-19) pandemic has resulted in shortages of personal protective equipment (PPE), underscoring the urgent need for simple, efficient, and inexpensive methods to decontaminate masks and respirators exposed to severe acute respiratory coronavirus virus 2 (SARS-CoV-2). We hypothesized that methylene blue (MB) photochemical treatment, which has various clinical applications, could decontaminate PPE contaminated with coronavirus.
Design:
The 2 arms of the study included (1) PPE inoculation with coronaviruses followed by MB with light (MBL) decontamination treatment and (2) PPE treatment with MBL for 5 cycles of decontamination to determine maintenance of PPE performance.
Methods:
MBL treatment was used to inactivate coronaviruses on 3 N95 filtering facepiece respirator (FFR) and 2 medical mask models. We inoculated FFR and medical mask materials with 3 coronaviruses, including SARS-CoV-2, and we treated them with 10 µM MB and exposed them to 50,000 lux of white light or 12,500 lux of red light for 30 minutes. In parallel, integrity was assessed after 5 cycles of decontamination using multiple US and international test methods, and the process was compared with the FDA-authorized vaporized hydrogen peroxide plus ozone (VHP+O3) decontamination method.
Results:
Overall, MBL robustly and consistently inactivated all 3 coronaviruses with 99.8% to >99.9% virus inactivation across all FFRs and medical masks tested. FFR and medical mask integrity was maintained after 5 cycles of MBL treatment, whereas 1 FFR model failed after 5 cycles of VHP+O3.
Conclusions:
MBL treatment decontaminated respirators and masks by inactivating 3 tested coronaviruses without compromising integrity through 5 cycles of decontamination. MBL decontamination is effective, is low cost, and does not require specialized equipment, making it applicable in low- to high-resource settings.
In this chapter I begin by examining some of the earliest legal documents to have been found, vassal treaties from the middle of the third millennium BCE. In the second section I analyze the most famous ancient “international” treaty: that struck between Egypt and the Hittite Kingdom in the second millennium BCE. In the third section I begin to explore the idea of compliance to treaties in the ancient world. In the fourth section I explore the specific use of oaths and threats as self-help in enforcement of ancient treaties. And in the final section, I discuss how trust was understood and encouraged in ancient times.
This is a study of what constituted legality and the role of law in ancient societies. Investigating and comparing legal codes and legal thinking of the ancient societies of Mesopotamia, Egypt, Greece, India, the Roman Republic, the Roman Empire and of the ancient Rabbis, this volume examines how people used law to create stable societies. Starting with Hammurabi's Code, this volume also analyzes the law of the pharaohs and the codes of the ancient rabbis and of the Roman Emperor Justinian. Focusing on the key concepts of justice equity and humaneness, the status of women and slaves, and the idea of criminality and of war and peace; no other book attempts to examine such diverse legal systems and legal thinking from the ancient world.
In both Jewish and Roman law of the first centuries of the new millennium, a striking change occurs, where a profession of scholars comes to prominence and even to have their opinions count as law.
It is often said that the Babylonian laws, especially the Laws of Hammurabi, are not as humane as other ancient laws such as the laws of the Bible, because Hammurabi’s laws track hierarchical social status rather than treating all equally before the law.
This chapter is about the origins of criminal law in ancient times. It is often claimed that ancient societies lack a conception of crime – treating all harms as civil wrongs (what we call “torts” today).
What is characteristic of some of international law is that there are rules that are seen to apply to most States, at least in a significant region of the world, and the rules have a bindingness that extends beyond the particular borders of those States.
One of the most metaphysically fraught concepts in legal thought is causation. Yet, despite being published in ancient Athens, the Tetralogies (attributed to Antiphon) provide a fascinating account of causation that even legal theorists today can appreciate.
As in many ancient societies, there were trials in ancient China and Greece. In Greece there were jury trials, but not for the first time historically.