Immune-Related Adverse Events in Patients with Lung Cancer.

PURPOSE OF REVIEW: Immune checkpoint inhibitors (ICI) have been widely adopted for the treatment of lung cancer since receiving first U.S Food and Drug Administration (FDA) approval in 2015. However, along with their use, the occurrence of immune-related adverse events (irAEs) has presented a challenge for both patients and oncology providers. In this manuscript, we reviewed the clinical trials that led to the approval of ICI by the FDA for the treatment of lung cancer between 2015 and 2023 to establish the frequency of irAEs in this patient population. Among the adverse events associated with ICI, we focused on the most common and relevant ones, including hypothyroidism, pneumonitis, diarrhea/colitis, skin rash, and hepatitis. RECENT FINDINGS: We thoroughly examined the available literature, including society guidelines concerning these complications, to discuss various aspects such as their pathophysiology, epidemiology, diagnostic process, grading system, and clinical management. Additionally, we explored the association between irAEs and disease response. The management of irAEs is a crucial aspect of oncologic care, particularly due to their potential to cause severe and life-threatening clinical manifestations. We present each pertinent aspect in a concise and organized manner to provide guidance and assistance to oncology providers managing these patients in both outpatient and inpatient settings.

Ab Initio Crystal Structure Prediction of the Energetic Materials LLM-105, RDX, and HMX.

Crystal structure prediction (CSP) is performed for the energetic materials (EMs) LLM-105 and α-RDX, as well as the α and ß conformational polymorphs of 1,3,5,7-tetranitro-1,3,5,7-tetraazacyclooctane (HMX), using the genetic algorithm (GA) code, GAtor, and its associated random structure generator, Genarris. Genarris and GAtor successfully generate the experimental structures of all targets. GAtor's symmetric crossover scheme, where the space group symmetries of parent structures are treated as genes inherited by offspring, is found to be particularly effective. However, conducting several GA runs with different settings is still important for achieving diverse samplings of the potential energy surface. For LLM-105 and α-RDX, the experimental structure is ranked as the most stable, with all of the dispersion-inclusive density functional theory (DFT) methods used here. For HMX, the α form was persistently ranked as more stable than the ß form, in contrast to experimental observations, even when correcting for vibrational contributions and thermal expansion. This may be attributed to insufficient accuracy of dispersion-inclusive DFT methods or to kinetic effects not considered here. In general, the ranking of some putative structures is found to be sensitive to the choice of the DFT functional and the dispersion method. For LLM-105, GAtor generates a putative structure with a layered packing motif, which is desirable thanks to its correlation with low sensitivity. Our results demonstrate that CSP is a useful tool for studying the ubiquitous polymorphism of EMs and shows promise of becoming an integral part of the EM development pipeline.

Performance of Dispersion-Inclusive Density Functional Theory Methods for Energetic Materials.

Molecular crystals of energetic materials (EMs) are denser than typical molecular crystals and are characterized by distinct intermolecular interactions between nitrogen-containing moieties. To assess the performance of dispersion-inclusive density functional theory (DFT) methods, we have compiled a data set of experimental sublimation enthalpies of 31 energetic materials. We evaluate the performance of three methods: the semilocal Perdew-Burke-Ernzerhof (PBE) functional coupled with the pairwise Tkatchenko-Scheffler (TS) dispersion correction, PBE with the many-body dispersion (MBD) method, and the PBE-based hybrid functional (PBE0) with MBD. Zero-point energy contributions and thermal effects are described using the quasi-harmonic approximation (QHA), including explicit treatment of thermal expansion, which we find to be non-negligible for EMs. The lattice energies obtained with PBE0+MBD are the closest to experimental sublimation enthalpies with a mean absolute error of 9.89 kJ/mol. However, the state-of-the-art treatment of vibrational and thermal contributions makes the agreement with experiment worse. Pressure-volume curves are also examined for six representative materials. For pressure-volume curves, all three methods provide reasonable agreement with experimental data with mean absolute relative errors of 3% or less. Most of the intermolecular interactions typical of EMs, namely nitro-amine, nitro-nitro, and nitro-hydrogen interactions, are more sensitive to the choice of the dispersion method than to the choice of the exchange-correlation functional. The exception is π-π stacking interactions, which are also very sensitive to the choice of the functional. Overall, we find that PBE+TS, PBE+MBD, and PBE0+MBD do not perform as well for energetic materials as previously reported for other classes of molecular crystals. This highlights the importance of testing dispersion-inclusive DFT methods for diverse classes of materials and the need for further method development.

Comparative study of group treatments for posttraumatic stress disorder.

Presented herein is a comparative study of group treatments for posttraumatic stress disorder (PTSD). In this study, an emerging intervention, memory specificity training (MeST), was compared with cognitive processing therapy (CPT) using standardized outcome measures of target symptoms (i.e., anxiety and depression from client perspective; memory specificity from independent rater perspective) and global functioning (independent rater perspective), as well as a process measure of expectancy (client perspective). Clients were assessed on 3 separate occasions: at baseline, posttreatment, and 3 months posttreatment. Adherence and treatment fidelity (independent rater perspective) were monitored throughout the course of both treatment conditions. Improvement in PTSD symptoms, depressive symptoms, and global functioning were similar between MeST and CPT; an increase in ability to specify memories upon retrieval was also similar between MeST and CPT. Positive reliable change was observed in both groups on all outcome measures. With respect to the primary target of PTSD symptoms, 88% of participants in both treatment groups moved into the functional distribution by posttreatment and maintained these gains at follow-up. Notably, compared with CPT, MeST required only half the dosage (i.e., number of sessions) to accomplish these gains. Illustrative vignettes from client-therapist exchanges are provided, and results are discussed in terms of the potential mechanisms of action. Implications for both clinical practice and clinical research are also included. (PsycINFO Database Record

A delay-discounting measure of preference for racial/ethnic matching in psychotherapy.

In this study, we sought to compare racial/ethnic minority participants' preference for racial/ethnic matching in psychotherapy with preferences for other methods of addressing cultural factors in treatment. Using a delay-discounting method, college students (331 racial/ethnic minority students from 2 universities) and a nationwide sample of self-reported clients (n = 77) were asked to indicate their strength of preference for 4 different methods for addressing culturally related variables in psychotherapy, including a desire to (a) work with a therapist whose race/ethnicity matches their own, (b) work with a therapist with a high level of multicultural training and experience, (c) receive a culturally adapted treatment, and (d) receive a therapist who is also a member of a racial/ethnic minority group, but not the same as the participant (i.e., a racial/ethnic minority pairing). We found that participants were willing to make significant sacrifices in treatment efficacy in order to receive each of the variables tested. In both samples, preferences were significantly stronger for therapist multicultural training/experience and use of culturally adapted treatments compared with racial/ethnic matching and racial/ethnic minority pairing. Further analyses indicated that clients expressed stronger preferences for racial/ethnic match and minority pairing than college student participants, and preference strength for 3 of the 4 scenarios was significantly related to strength of minority culture identification. The results of this study have important implications for preference accommodation in psychotherapy with racial/ethnic minority individuals.

Impact of psychotherapist expectations on client outcomes.

Recent investigations have implicated client expectations of psychotherapy as a strong predictor of premature termination; however, there is reason to believe psychotherapist expectations may also impact client outcomes. This study sought to address this gap in the literature by examining the association of psychotherapists' expectations to clients' psychotherapy outcomes, including termination status. Participants were 54 current and recent trainee psychotherapists at a Southern public university, who completed delay discounting measures to assess their expectations of the effectiveness of psychotherapy. Data were also drawn from 300 adult clients who had received at least 2 sessions of individual psychotherapy from the participating psychotherapists of this study, and had previously completed the Outcome Questionnaire 45.2 prior to each individual therapy session. Psychotherapists were found to hold significantly higher expectations for client improvement than anticipated, based on existing literature, and these high expectations were found to be positively correlated with clinically significant change in clients. Moreover, psychotherapists' expectations were found to explain 7.3% of the explainable variance in whether or not clients experienced clinically significant change during psychotherapy. Implications for improving client retention and treatment outcome are discussed.