TURALIO® Risk Evaluation and Mitigation Strategy Program (tREMS): 3-year retrospective hepatic safety assessment.

Aim: Hepatic safety data assessment from the TURALIO® (pexidartinib) Risk Evaluation and Mitigation Strategy (tREMS) Program. Methods: Retrospective 3-year assessment (August 2019 to June 2022) of hepatic events from the TURALIO® (pexidartinib) Risk Evaluation and Mitigation Strategy Program. Results: A total of 451 patients, 369 prescribers, 2 wholesalers/distributors and 2 pharmacies were enrolled and certified. Twenty-one (4.7%) patients met the criteria for a hepatic adverse event or laboratory abnormality suggestive of serious and potentially fatal liver injury, all with onset within 2 months of therapy. No new hepatic safety signals were identified. Conclusion: Results are consistent with the phase 3 ENLIVEN trial data. Liver enzyme monitoring, combined with early intervention, including dose modification and discontinuation, conducted in patients treated with pexidartinib mitigate the risk of potential hepatotoxicity.

Safety findings from the 3-year data collected in the TURALIO^® Risk Evaluation and Mitigation Strategy ProgramPexidartinib (TURALIO^®) is an oral drug that is used to treat adults with tenosynovial giant cell tumor (TGCT) that cannot be fixed with surgery. TGCTs are rare, noncancerous tumors that cause pain, stiffness and difficulty moving. Pexidartinib works by blocking a protein that helps these tumors grow. Before pexidartinib, there were no good treatments for TGCT and surgery often could not remove all the tumors, so they would frequently grow back.Pexidartinib was approved in 2019 after a clinical trial showed it worked well in adults with TGCT. However, pexidartinib can sometimes cause serious liver harm for some patients. To handle this risk, a program called the tREMS (TURALIO^® Risk Evaluation and Mitigation Strategy) was established to ensure that pexidartinib is used safely.The tREMS Program teaches doctors, pharmacists and patients about the safe use of pexidartinib and potential liver risks and enrolls patients in a registry to watch their health. Doctors and pharmacies must be certified, and patients need regular liver tests. In the first 3 years, 451 patients and 369 doctors joined the program. Unintended liver issues were found in around 5% of patients, a rate that is about the same as that seen in pexidartinib clinical trials, and no new safety concerns were found. About half of patients with liver issues could reverse them by stopping pexidartinib. No patient had permanent liver damage, needed a transplant or died from liver problems. These results show that the tREMS Program is working well to keep patients with TGCT safe while taking pexidartinib.

Using Active Learning Strategies to Strengthen Cultural and Linguistic Diversity Training in Communication Sciences and Disorders Programs.

Purpose: Training in cultural competence is an accreditation requirement for graduate programs in Communication Sciences and Disorders (CSD; Council on Academic Accreditation in Audiology and Speech-Language Pathology, 2020). Cultural and linguistic diversity (CLD) instruction within CSD programs and current instructional models may not provide students with effective training in this area (Hammond et al., 2009; Higby et al., 2021; Stockman et al., 2008). In this paper, we present active learning as an instructional approach that may provide students with stronger training in the assessment and treatment of individuals with unfamiliar cultural and linguistic backgrounds. Conclusions: Active learning emphasizes the creation of a supportive classroom environment, teaching skills rather than content, and fostering metacognition in students (Bransford et al., 2000; Gooblar, 2019). We propose a three-part pedagogical model for using active learning strategies to improve clinical training in assessment and treatment of clients with CLD backgrounds. This pedagogical model encourages instructors to set the scene for learning, present a problem to solve, and build in reflection and generalization. Active learning approaches, as described in the model, are ideal for teaching clinical problem-solving across populations while reflecting on one's lived experience and positionality. Sample materials for readers to create their own lesson plans using the model are provided and reviewed.

A Phase I, Multicenter, Open-Label, First-in-Human Study of DS-6157a in Patients with Advanced Gastrointestinal Stromal Tumor.

PURPOSE: To evaluate DS-6157a, an antibody-drug conjugate targeting G protein-coupled receptor 20 (GPR20), in gastrointestinal stromal tumors (GIST). PATIENTS AND METHODS: In this phase I multicenter, open-label, multiple-dose study, patients with previously treated advanced GIST received intravenous DS-6157a on Day 1 of 21-day cycles, with a starting dose of 1.6 mg/kg. The primary objective evaluated the safety and tolerability of DS-6157a, while determining dose-limiting toxicity (DLT) and the MTD. Secondary objectives included plasma pharmacokinetics parameters, plasma antidrug antibodies (ADA), and efficacy. RESULTS: A total of 34 patients enrolled. DS-6157a was well tolerated, with DLTs in 4 patients (11.8%) at doses of 6.4 mg/kg, 9.6 mg/kg, and 12.8 mg/kg; the MTD was determined to be 6.4 mg/kg. Treatment-emergent adverse events (TEAE) grade ≥3 occurred in 17 patients (50.0%), including decreased platelet count (23.5%), anemia (20.6%), decreased neutrophil count (14.7%), and decreased white blood cell count (11.8%). Four patients (11.8%) experienced serious adverse events related to DS-6157a. Six patients died with 5 due to disease progression and 1 due to DS-6157a-related TEAE. Tumor shrinkage was observed in 7 patients (20.6%), and 1 patient (2.9%) achieved a partial response. Plasma concentrations and exposure of intact DS-6157a, DXd, and total anti-GPR20 antibody all demonstrated a dose-dependent profile. No treatment-emergent ADAs were observed. CONCLUSIONS: Targeting GPR20 with DS-6157a was tolerated in patients with advanced GIST with tumor shrinkage demonstrated in KIT/PDGFRA wild-type GIST. However, the study did not proceed further due to lower efficacy outcomes than anticipated.

Assessing Shared Reading in Families at Risk: Does Quantity Predict Quality?

PURPOSE: Quantity and quality of early at-home reading shape literacy outcomes. At-home reading frequency is a common outcome measure in interventions. This single measure may not fully capture the quality of early reading interactions, such as parent and child references to print, an important contributor to language and literacy outcomes. This study aims to evaluate if and how reported reading frequency and duration are associated with parent and child print referencing, controlling for perceived parenting self-efficacy, developmental knowledge, and child sex. METHOD: This study is a secondary analysis of baseline data from a treatment study with parents (N = 30) and children (1;1-2;3 [years;months]) from underresourced households. Parents reported weekly reading episode frequency and duration (in minutes). We coded parent-child book-sharing interactions to quantify use of print references. RESULTS: Negative binomial regression modeling suggested that parents who reported more weekly reading episodes tended to use more print references during interactions. However, reported reading time in minutes was not significantly associated with parents' print referencing. Parents' print references were also associated with perceived self-efficacy, developmental knowledge, and child sex. In our sample, parents used more print references with male children. Neither reading frequency nor reading time was associated with increased print referencing from children. CONCLUSIONS: Duration of reading did not positively predict children's use of print references. However, weekly reading frequency positively predicted parents' use of print references. Parent perceived self-efficacy and knowledge may predict early interaction quality similarly to quantity of reading. SUPPLEMENTAL MATERIAL: https://doi.org/10.23641/asha.20669094.

Preschoolers' Word-Learning During Storybook Reading Interactions: Comparing Repeated and Elaborated Input.

Purpose Previous research shows that shared storybook reading interactions can function as effective speech and language interventions for young children, helping to improve a variety of skills-including word-learning. This study sought to investigate the potential benefits of elaboration of new words during a single storybook reading with preschoolers. Method Thirty-three typically developing children ages 35-37 months listened to a storybook containing novel words that were either repeated with a definition, repeated with no additional information, or only said once. Their receptive word-learning for these novel words was then evaluated via a preferential looking task. We analyzed children's correct looks to target pictures and compared looking behavior across the three levels of presentation. Results Results showed that preschoolers demonstrated successful receptive word-learning after a single storybook reading interaction with an adult when target words were repeated, either with or without elaboration. Within this context, elaboration was not required for preschoolers' receptive word-learning. Conclusions These results support the use of storybook reading with young children as a way to foster early receptive word-learning and highlight the importance of repeated exposure to novel material either with or without additional semantic information.