Real-life use of talimogene laherparepvec (T-VEC) in melanoma patients in centers in Austria, Switzerland and Germany.

Talimogene laherparepvec (T-VEC) is a licensed therapy for use in melanoma patients of stage IIIB-IVM1a with injectable, unresectable metastatic lesions in Europe. Approval was based on the Oncovex Pivotal Trial in Melanoma study, which also included patients with distant metastases and demonstrated an overall response rate (ORR) of 40.5% and a complete response (CR) rate of 16.6%. The aim of this study was to assess the outcome of melanoma patients treated with T-VEC in a real-life clinical setting. Based on data from 10 melanoma centers in Austria, Switzerland and southern Germany, we conducted a retrospective chart review, which included 88 patients (44 male, 44 female) with a median age of 72 years (range 36-95 years) treated with T-VEC during the period from May 2016 to January 2020. 88 patients fulfilled the inclusion criteria for analysis. The ORR was 63.7%. 38 patients (43.2%) showed a CR, 18 (20.5%) had a partial response, 8 (9.1%) had stable disease and 24 (27.3%) patients had a progressive disease. The median treatment period was 19 weeks (range: 1-65), an average of 11 doses (range: 1-36) were applied. 39 (45.3%) patients developed adverse events, mostly mild, grade I (64.1%). This real-life cohort treatment with T-VEC showed a high ORR and a large number of durable CRs

Predicting at-risk opioid use three months after ed visit for trauma: Results from the AURORA study

OBJECTIVE: Whether short-term, low-potency opioid prescriptions for acute pain lead to future at-risk opioid use remains controversial and inadequately characterized. Our objective was to measure the association between emergency department (ED) opioid analgesic exposure after a physical, trauma-related event and subsequent opioid use. We hypothesized ED opioid analgesic exposure is associated with subsequent at-risk opioid use. METHODS: Participants were enrolled in AURORA, a prospective cohort study of adult patients in 29 U.S., urban EDs receiving care for a traumatic event. Exclusion criteria were hospital admission, persons reporting any non-medical opioid use (e.g., opioids without prescription or taking more than prescribed for euphoria) in the 30 days before enrollment, and missing or incomplete data regarding opioid exposure or pain. We used multivariable logistic regression to assess the relationship between ED opioid exposure and at-risk opioid use, defined as any self-reported non-medical opioid use after initial ED encounter or prescription opioid use at 3-months. RESULTS: Of 1441 subjects completing 3-month follow-up, 872 participants were included for analysis. At-risk opioid use occurred within 3 months in 33/620 (5.3%, CI: 3.7,7.4) participants without ED opioid analgesic exposure; 4/16 (25.0%, CI: 8.3, 52.6) with ED opioid prescription only; 17/146 (11.6%, CI: 7.1, 18.3) with ED opioid administration only; 12/90 (13.3%, CI: 7.4, 22.5) with both. Controlling for clinical factors, adjusted odds ratios (aORs) for at-risk opioid use after ED opioid exposure were: ED prescription only: 4.9 (95% CI 1.4, 17.4); ED administration for analgesia only: 2.0 (CI 1.0, 3.8); both: 2.8 (CI 1.2, 6.5). CONCLUSIONS: ED opioids were associated with subsequent at-risk opioid use within three months in a geographically diverse cohort of adult trauma patients. This supports need for prospective studies focused on the long-term consequences of ED opioid analgesic exposure to estimate individual risk and guide therapeutic decision-making

The AURORA Study: a longitudinal, multimodal library of brain biology and function after traumatic stress exposure

Adverse posttraumatic neuropsychiatric sequelae (APNS) are common among civilian trauma survivors and military veterans. These APNS, as traditionally classified, include posttraumatic stress, postconcussion syndrome, depression, and regional or widespread pain. Traditional classifications have come to hamper scientific progress because they artificially fragment APNS into siloed, syndromic diagnoses unmoored to discrete components of brain functioning and studied in isolation. These limitations in classification and ontology slow the discovery of pathophysiologic mechanisms, biobehavioral markers, risk prediction tools, and preventive/treatment interventions. Progress in overcoming these limitations has been challenging because such progress would require studies that both evaluate a broad spectrum of posttraumatic sequelae (to overcome fragmentation) and also perform in-depth biobehavioral evaluation (to index sequelae to domains of brain function). This article summarizes the methods of the Advancing Understanding of RecOvery afteR traumA (AURORA) Study. AURORA conducts a large-scale (n = 5000 target sample) in-depth assessment of APNS development using a state-of-the-art battery of self-report, neurocognitive, physiologic, digital phenotyping, psychophysical, neuroimaging, and genomic assessments, beginning in the early aftermath of trauma and continuing for 1 year. The goals of AURORA are to achieve improved phenotypes, prediction tools, and understanding of molecular mechanisms to inform the future development and testing of preventive and treatment interventions

War, trauma and children's development: observations from a modern evolutionary perspective

Lethal intergroup conflict has been part of the human experience ever since our species emerged on the African savannah. Modern evolutionary thinking suggests that children's development could have evolved a variety of responses to it, some of which are highlighted upon considering, from the field of behavioural ecology, life-history theory and, derived from it, Belsky, Steinberg and Draper's (1991) evolutionary theory of socialization. This speculative essay examines the implications of such thinking, specifically with regard to insecure attachment, anxiety, depression, aggression, pubertal and sexual development, as well as mating and parenting. Considered, too, are issues of intergenerational transmission and variation in developmental reactivity to exposure to deadly political violence of the ethnic-cleansing variety in childhood

The Near-Earth Object Surveyor Mission

The Near-Earth Object (NEO) Surveyor mission is a NASA Observatory designed to discover and characterize asteroids and comets. The mission’s primary objective is to find the majority of objects large enough to cause severe regional impact damage (>140 m in effective spherical diameter) within its 5 yr baseline survey. Operating at the Sun-Earth L1 Lagrange point, the mission will survey to within 45° of the Sun in an effort to find objects in the most Earth-like orbits. The survey cadence is optimized to provide observational arcs long enough to distinguish near-Earth objects from more distant small bodies that cannot pose an impact hazard reliably. Over the course of its survey, NEO Surveyor will discover ∼200,000-300,000 new NEOs down to sizes as small as ∼10 m and thousands of comets, significantly improving our understanding of the probability of an Earth impact over the next century. © 2023. The Author(s). Published by the American Astronomical Society.Open access journalThis item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at [email protected]