Durvalumab Treatment Patterns for Patients with Unresectable Stage III Non-Small Cell Lung Cancer in the Veterans Health Administration (VHA): A Nationwide, Real-World Study.

BACKGROUND: Durvalumab is approved for the treatment of adults with unresectable stage III non-small cell lung cancer (NSCLC) post-chemoradiotherapy (CRT). This real-world study describes patient characteristics and durvalumab treatment patterns (number of doses and therapy duration; treatment initiation delays, interruptions, discontinuations, and associated reasons) among VHA-treated patients. METHODS: This was a retrospective cohort study of adults with unresectable stage III NSCLC receiving durvalumab at the VHA between 1 January 2017 and 30 June 2020. Patient characteristics and treatment patterns were presented descriptively. RESULTS: A total of 935 patients were included (median age: 69 years; 95% males; 21% Blacks; 46% current smokers; 16% ECOG performance scores ≥ 2; 50% squamous histology). Durvalumab initiation was delayed in 39% of patients (n = 367). Among the 200 patients with recorded reasons, delays were mainly due to physician preference (20%) and CRT toxicity (11%). Overall, patients received a median (interquartile range) of 16 (7-24) doses of durvalumab over 9.0 (2.9-11.8) months. Treatment interruptions were experienced by 19% of patients (n = 180), with toxicity (7.8%) and social reasons (2.6%) being the most cited reasons. Early discontinuation occurred in 59% of patients (n = 551), largely due to disease progression (24.2%) and toxicity (18.2%). CONCLUSIONS: These real-world analyses corroborate PACIFIC study results in terms of the main reasons for treatment discontinuation in a VHA population with worse prognostic factors, including older age, predominantly male sex, and poorer performance score. One of the main reasons for durvalumab initiation delays, treatment interruptions, or discontinuations was due to toxicities. Patients could benefit from improved strategies to prevent, identify, and manage CRT and durvalumab toxicities timely and effectively.

Inclusion of postdoctoral trainees in a translational science training TL1 program was associated with greater diversification of research across the translational science continuum: a bibliometric analysis of TL1 trainee publications.

The NIH National Center for Advancing Translational Science (NCATS) was established to support translational research that spans the entire TS Continuum, with the goal of bridging the gap between preclinical biomedical research and real-world applications to advance treatments to patients more quickly. In 2018, the Translational Science Training (TST) TL1 Program at the University of Texas Health Science Center at San Antonio implemented new strategies to better include and encourage research more broadly across the TS Continuum, including the addition of postdoctoral scientists and a clinically trained Program Co-Director, expansion of team science and community engagement programming, and targeted trainee recruitment from schools of nursing, dentistry, and allied health, in addition to medicine. The objective of this bibliometric analysis was to determine if the program exhibited a more diverse mix of T-types after the adjustments made in 2018. The TST/TL1 Program experienced a shift in T-type, from mostly T0 (preclinical) to more T3/T4 (clinical implementation/public health) research, after new strategies were implemented. This supports the conclusion that strategic programmatic adjustments by an NCATS-funded predoctoral training program resulted in outcomes that better align with NCATS priorities to develop Trainees who contribute across the entire TS Continuum.

Health Equity in Patients Receiving Durvalumab for Unresectable Stage III Non-Small Cell Lung Cancer in the US Veterans Health Administration.

BACKGROUND: Real-world evidence is limited regarding the relationship between race and use of durvalumab, an immunotherapy approved for use in adults with unresectable stage III non-small cell lung cancer (NSCLC) post-chemoradiotherapy (CRT). This study aimed to evaluate if durvalumab treatment patterns differed by race in patients with unresectable stage III NSCLC in a Veterans Health Administration (VHA) population. MATERIALS AND METHODS: This was a retrospective analysis of White and Black adults with unresectable stage III NSCLC treated with durvalumab presenting to any VHA facility in the US from January 1, 2017, to June 30, 2020. Data captured included baseline characteristics and durvalumab treatment patterns, including treatment initiation delay (TID), interruption (TI), and discontinuation (TD); defined as CRT completion to durvalumab initiation greater than 42 days, greater than 28 days between durvalumab infusions, and more than 28 days from the last durvalumab dose with no new durvalumab restarts, respectively. The number of doses, duration of therapy, and adverse events were also collected. RESULTS: A total of 924 patients were included in this study (White = 726; Black = 198). Race was not a significant factor in a multivariate logistic regression model for TID (OR, 1.39; 95% CI, 0.81-2.37), TI (OR, 1.58; 95% CI, 0.90-2.76), or TD (OR, 0.84; 95% CI, 0.50-1.38). There were also no significant differences in median (interquartile range [IQR]) number of doses (White: 15 [7-24], Black: 18 [7-25]; P = .25) or median (IQR) duration of therapy (White: 8.7 months [2.9-11.8], Black: 9.8 months [3.6-12.0]; P = .08), although Black patients were less likely to experience an immune-related adverse event (28% vs. 36%, P = .03) and less likely to experience pneumonitis (7% vs. 14%, P < .01). CONCLUSION: Race was not found to be linked with TID, TI, or TD in this real-world study of patients with unresectable stage III NSCLC treated with durvalumab at the VHA.

Health disparity in use of novel agents for first-line therapy in Black and White patients with chronic lymphocytic leukemia in the Department of Veterans Affairs.

BACKGROUND: Novel agents (NAs) (ibrutinib, idelalisib, and venetoclax) were first introduced in 2013 as therapeutic options to treat chronic lymphocytic leukemia (CLL). OBJECTIVES: To determine if the uptake of NAs for first-line treatment was similar in Black and White patients with CLL treated in the Department of Veterans Affairs (VA). METHODS: We conducted a retrospective cohort study including adults with CLL managed in the VA from October 1, 2013, to September 30, 2017. Descriptive statistics were used to summarize demographic data, and appropriate bivariable statistical tests were used to compare NA use, baseline characteristics, health outcomes, and complications. A multivariable logistic regression model was used to identify factors associated with uptake of NAs. The study included 565 patients; 86% were White and 14% were Black. Black patients were younger than White patients (median age [66 vs 69 years; P < 0.01]) but had similar median baseline Charlson comorbidity scores (4 vs 5). RESULTS: Overall, Black patients were less likely to receive NAs than White patients (14% vs 26%; P = 0.02). The gap narrowed over the study period: 4% vs 17% (2014), 13% vs 25% (2015), 17% vs 33% (2016), and 31% vs 33% (2017). Black race (P = 0.02) and fiscal year (P < 0.01) were the only variables significantly associated with NA use in the multivariable model. Health outcomes and most complications were similar for Black and White patients despite the difference in prescribing patterns. CONCLUSIONS: This is the first study to identify a potential health disparity with respect to use of NAs among Black and White patients with CLL treated in the VA. Fortunately, health outcomes and most complications were similar for Black and White patients despite the difference in prescribing patterns. DISCLOSURES: Funding for the study was provided by AstraZeneca as a research grant to the Foundation for Advancing Veterans' Health Research (FAVHR), a non-profit entity within the Audie L. Murphy Veterans Hospital, San Antonio, TX. Drs Nooruddin and Frei have received research grants (paid to FAVHR) from AstraZeneca in the last 3 years. Ms Ryan is an employee of AstraZeneca. The views expressed in this article are those of the authors and do not necessarily represent the views of the Department of Veterans Affairs, the National Institutes of Health, or the authors' affiliated institutions.

Comparison of bibliometrics for predoctoral Translational Science Training (TST) TL1 Program participants and nonparticipants, male and female participants, and participants from underrepresented and well-represented backgrounds.

Research education and training in Translational Science develops and sustains a workforce to efficiently advance studies designed to improve human health. We evaluated the effectiveness of a Translational Science Training (TST) TL1 Program. Participants had significantly better publications/year, citations/year, h-index, and m-quotient than nonparticipants. Female and male participants, and participants from underrepresented and well-represented backgrounds, performed similarly on all bibliometric assessments. Finally, TST/TL1 Program participants outperformed students from other PhD programs at our institution. This analysis suggests that the TST/TL1 Program has been effective for participants, including those who are female and from underrepresented backgrounds.

Unhappy or unsatisfied: distinguishing the role of negative affect and need frustration in depressive symptoms over the academic year and during the COVID-19 pandemic.

Mental health problems are becoming increasingly prevalent across college campuses. Past research has found that negative affect and frustration of basic psychological needs contribute to the development of depressive symptoms, but there is limited research which compares whether these are antecedents or concomitants of depressive symptoms. The present set of studies aimed to distinguish the differential associations of affect and need frustration on depressive symptoms. Students (Nstudy1 = 379; Nstudy2 = 235) completed measures on negative affect, need frustration (e.g., relatedness, competence, and autonomy), and depressive symptoms over an academic year and during the start of the COVID-19 pandemic. In both samples, fully cross-lagged path models were used to examine the relation between need frustration, negative affect, and depressive symptoms over time. Across both studies, basic psychological need frustration was the only consistent predictor of both negative affect and depressive symptoms over time, suggesting that need frustration is an antecedent of depressive symptoms over time, and especially during vulnerable time periods. Additionally, in Study 2, reports from close others confirm that need frustration is the largest indicator of depressive presentation in students. These results highlight the relative importance of basic psychological need frustration in predicting depressive symptoms in university students.

Tandem Homologation-Acylation Chemistry: Single and Double Homologation.

Treatment of ß-dicarbonyls with the Furakawa-variant of the Simmons-Smith reagent results in homologation and production of an intermediate zinc enolate. Treatment of the enolate with various acylating agents generate products with both γ-dicarbonyl functionality and ß-dicarbonyl functionality. In situ exposure of the acylated product to additional zinc carbenoid effects a second regiospecific homologation reaction.

Polarizabilities of adsorbed and assembled molecules: measuring the conductance through buried contacts.

We have measured the polarizabilities of four families of molecules adsorbed to Au{111} surfaces, with structures ranging from fully saturated to fully conjugated, including single-molecule switches. Measured polarizabilities increase with increasing length and conjugation in the adsorbed molecules and are consistent with theoretical calculations. For single-molecule switches, the polarizability reflects the difference in substrate-molecule electronic coupling in the ON and OFF conductance states. Calculations suggest that the switch between the two conductance states is correlated with an oxidation state change in a nitro functional group in the switch molecules.

Functional and spectroscopic measurements with scanning tunneling microscopy.

Invented as a surface analytical technique capable of imaging individual atoms and molecules in real space, scanning tunneling microscopy (STM) has developed and advanced into a technique able to measure a variety of structural, functional, and spectroscopic properties and relationships at the single-molecule level. Here, we review basic STM operation and image interpretation, techniques developed to manipulate single atoms and molecules with the STM to measure functional properties of surfaces, local spectroscopies used to characterize atoms and molecules at the single-molecule level, and surface perturbations affecting surface coverage and surface reactions. Each section focuses on determining the identity and function of chemical species so as to elucidate information beyond topography with STM.

Molecular engineering and measurements to test hypothesized mechanisms in single molecule conductance switching.

Six customized phenylene-ethynylene-based oligomers have been studied for their electronic properties using scanning tunneling microscopy to test hypothesized mechanisms of stochastic conductance switching. Previously suggested mechanisms include functional group reduction, functional group rotation, backbone ring rotation, neighboring molecule interactions, bond fluctuations, and hybridization changes. Here, we test these hypotheses experimentally by varying the molecular designs of the switches; the ability of the molecules to switch via each hypothetical mechanism is selectively engineered into or out of each molecule. We conclude that hybridization changes at the molecule-surface interface are responsible for the switching we observe.

Cross-step place-exchange of oligo(phenylene-ethynylene) molecules.

We have observed nitro-functionalized oligo(phenylene-ethynylene) molecules exhibiting motion up and down Au{111} substrate monatomic step edges within host self-assembled monolayers of n-alkanethiols, independent of previously observed conductance switching. Single molecules have been imaged with scanning tunneling microscopy to place-exchange reversibly between the top and bottom of monatomic substrate step edges.