Intersection of Palliative Care and Hospice Use Among Patients With Advanced Lung Cancer.

Background: Hospice and palliative care (PC) are important components of lung cancer care and independently provide benefits to patients and their families. Objective: To better understand the relationship between hospice and PC and factors that influence this relationship. Methods: A retrospective cohort study of patients diagnosed with advanced lung cancer (stage IIIB/IV) within the U.S. Veterans Health Administration (VA) from 2007 to 2013 with follow-up through 2017 (n = 22,907). Mixed logistic regression models with a random effect for site, adjustment for patient variables, and propensity score weighting were used to examine whether the association between PC and hospice use varied by U.S. region and PC team characteristics. Results: Overall, 57% of patients with lung cancer received PC, 69% received hospice, and 16% received neither. Of those who received hospice, 60% were already enrolled in PC. Patients who received PC had higher odds of hospice enrollment than patients who did not receive PC (adjusted odds ratio = 3.25, 95% confidence interval: 2.43-4.36). There were regional differences among patients who received PC; the predicted probability of hospice enrollment was 85% and 73% in the Southeast and Northeast, respectively. PC team and facility characteristics influenced hospice use in addition to PC; teams with the shortest duration of existence, with formal team training, and at lower hospital complexity were more likely to use hospice (all p < 0.05). Conclusions: Among patients with advanced lung cancer, PC was associated with hospice enrollment. However, this relationship varied by geographic region, and PC team and facility characteristics. Our findings suggest that regional PC resource availability may contribute to substitution effects between PC and hospice for end-of-life care.

"You're Socially Distant and Trying Not to Be Emotionally Distant." Physicians' Perspectives of Communication and Therapeutic Relationships in the ICU During the COVID-19 Pandemic: A Qualitative Study.

To: 1) characterize how COVID-19-related policies influence patient-clinician communication and relationships in the ICU, with attention to race and ethnicity as factors and 2) identify interventions that may facilitate patient-clinician communication. DESIGN: We conducted a qualitative study between September 2020 and February 2021 that explored facilitators and barriers to patient-clinician communication and the formation of therapeutic relationships. We used thematic analysis to develop findings describing patient-communication and therapeutic relationships within the ICU early in the COVID-19 pandemic. SETTING: We purposively selected hospital dyads from regions in the United States that experienced early and/or large surges of patients hospitalized with COVID-19. SUBJECTS: We recruited a national sample of ICU physicians from Veteran Affairs (VA) Health Care Systems and their associated academic affiliate hospitals. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Twenty-four intensivists from seven VA hospitals and six academic-affiliate hospitals participated. Intensivists noted the disproportionate impact of the pandemic on among people holding minoritized racial and ethnic identities, describing how language barriers and restrictive visitation policies exacerbated institutional mistrust and compromised physicians' ability to develop therapeutic relationships. We also identified several perceived influences on patient-clinician communication and the establishment of therapeutic relationships. Barriers included physicians' fear of becoming infected with COVID-19 and use of personal protective equipment, which created obstacles to effective physical and verbal interactions. Facilitators included the presence of on-site interpreters, use of web-based technology to interact with family members outside the ICU, and designation of a care team member or specialist service to provide routine updates to families. CONCLUSIONS: The COVID-19 pandemic has threatened patient-clinician communication and the development of therapeutic relationships in the ICU, particularly among people holding minoritized racial and ethnic identities and their families. We identified several facilitators to improve patient-clinician communication as perceived by intensivists that may help improve trust and foster therapeutic alliances.

Examining the Relationship between Pre-Malignant Breast Lesions, Carcinogenesis and Tumor Evolution in the Mammary Epithelium Using an Agent-Based Model.

INTRODUCTION: Breast cancer, the product of numerous rare mutational events that occur over an extended time period, presents numerous challenges to investigators interested in studying the transformation from normal breast epithelium to malignancy using traditional laboratory methods, particularly with respect to characterizing transitional and pre-malignant states. Dynamic computational modeling can provide insight into these pathophysiological dynamics, and as such we use a previously validated agent-based computational model of the mammary epithelium (the DEABM) to investigate the probabilistic mechanisms by which normal populations of ductal cells could transform into states replicating features of both pre-malignant breast lesions and a diverse set of breast cancer subtypes. METHODS: The DEABM consists of simulated cellular populations governed by algorithms based on accepted and previously published cellular mechanisms. Cells respond to hormones, undergo mitosis, apoptosis and cellular differentiation. Heritable mutations to 12 genes prominently implicated in breast cancer are acquired via a probabilistic mechanism. 3000 simulations of the 40-year period of menstrual cycling were run in wild-type (WT) and BRCA1-mutated groups. Simulations were analyzed by development of hyperplastic states, incidence of malignancy, hormone receptor and HER-2 status, frequency of mutation to particular genes, and whether mutations were early events in carcinogenesis. RESULTS: Cancer incidence in WT (2.6%) and BRCA1-mutated (45.9%) populations closely matched published epidemiologic rates. Hormone receptor expression profiles in both WT and BRCA groups also closely matched epidemiologic data. Hyperplastic populations carried more mutations than normal populations and mutations were similar to early mutations found in ER+ tumors (telomerase, E-cadherin, TGFB, RUNX3, p < .01). ER- tumors carried significantly more mutations and carried more early mutations in BRCA1, c-MYC and genes associated with epithelial-mesenchymal transition. CONCLUSIONS: The DEABM generates diverse tumors that express tumor markers consistent with epidemiologic data. The DEABM also generates non-invasive, hyperplastic populations, analogous to atypia or ductal carcinoma in situ (DCIS), via mutations to genes known to be present in hyperplastic lesions and as early mutations in breast cancers. The results demonstrate that agent-based models are well-suited to studying tumor evolution through stages of carcinogenesis and have the potential to be used to develop prevention and treatment strategies.

Examining the pathogenesis of breast cancer using a novel agent-based model of mammary ductal epithelium dynamics.

The study of the pathogenesis of breast cancer is challenged by the long time-course of the disease process and the multi-factorial nature of generating oncogenic insults. The characterization of the longitudinal pathogenesis of malignant transformation from baseline normal breast duct epithelial dynamics may provide vital insight into the cascading systems failure that leads to breast cancer. To this end, extensive information on the baseline behavior of normal mammary epithelium and breast cancer oncogenesis was integrated into a computational model termed the Ductal Epithelium Agent-Based Model (DEABM). The DEABM is composed of computational agents that behave according to rules established from published cellular and molecular mechanisms concerning breast duct epithelial dynamics and oncogenesis. The DEABM implements DNA damage and repair, cell division, genetic inheritance and simulates the local tissue environment with hormone excretion and receptor signaling. Unrepaired DNA damage impacts the integrity of the genome within individual cells, including a set of eight representative oncogenes and tumor suppressors previously implicated in breast cancer, with subsequent consequences on successive generations of cells. The DEABM reproduced cellular population dynamics seen during the menstrual cycle and pregnancy, and demonstrated the oncogenic effect of known genetic factors associated with breast cancer, namely TP53 and Myc, in simulations spanning ∼40 years of simulated time. Simulations comparing normal to BRCA1-mutant breast tissue demonstrated rates of invasive cancer development similar to published epidemiologic data with respect to both cumulative incidence over time and estrogen-receptor status. Investigation of the modeling of ERα-positive (ER+) tumorigenesis led to a novel hypothesis implicating the transcription factor and tumor suppressor RUNX3. These data suggest that the DEABM can serve as a potentially valuable framework to augment the traditional investigatory workflow for future hypothesis generation and testing of the mechanisms of breast cancer oncogenesis.

Impact of antigenic and genetic drift on the serologic surveillance of H5N2 avian influenza viruses.

BACKGROUND: Serologic surveillance of Avian Influenza (AI) viruses is carried out by the hemagglutination inhibition (HI) test using reference reagents. This method is recommended by animal health organizations as a standard test to detect antigenic differences (subtypes) between circulating influenza virus, vaccine- and/or reference- strains. However, significant discrepancies between reference antisera and field isolates have been observed during serosurveillance of influenza A viruses in pig and poultry farms. The objective of this study was to examine the effects of influenza virus genetic and antigenic drift on serologic testing using standard HI assays and reference reagents. Low pathogenic AI H5N2 viruses isolated in Mexico between 1994 and 2008 were used for phylogenetic analysis of AI hemagglutinin genes and for serologic testing using antisera produced with year-specific AI virus isolates. RESULTS: Phylogenetic analysis revealed significant divergence between early LPAI H5N2 viruses (1994 - 1998) and more recent virus field isolates (2002 - 2008). Results of the HI test were markedly influenced by the selection of the AI H5N2 virus (year of isolation) used as reference antigen for the assay. These analyses indicate that LPAI H5N2 viruses in Mexico are constantly undergoing genetic drift and that serosurveillance of AI viruses is significantly influenced by the antigen or antisera used for the HI test. CONCLUSIONS: Reference viral antigens and/or antisera need to be replaced constantly during surveillance of AI viruses to keep pace with the AI antigenic drift. This strategy should improve the estimation of antigenic differences between circulating AI viruses and the selection of suitable vaccine strains.