Co-Occurring Alterations in Multiple Tumor Suppressor Genes Are Associated With Worse Outcomes in Patients With EGFR-Mutant Lung Cancer.

INTRODUCTION: Patients with metastatic EGFR-mutant NSCLC inevitably have disease progression while on tyrosine kinase inhibitor (TKI) therapy. Co-occurring tumor suppressor gene (TSG) alterations have been associated with poor outcomes, however, detailed analyses of their impact on patient outcomes are limited. METHODS: Patients with EGFR-mutant NSCLC treated with EGFR TKIs who had tumor genomic profiling were included. Alterations in TP53 and five additional TSGs (RB1, NF1, ARID1A, BRCA1, and PTEN) were used to stratify the cohort into the following three subgroups: patients with tumors harboring a TP53 mutation plus a mutation in at least one additional TSG (TP53mut/TSGmut), those having a TP53 mutation without additional TSG mutations (TP53mut/TSGwt), and those with TP53wt. Patient characteristics and clinical outcomes were assessed in two independent cohorts. RESULTS: A total of 101 patients from the Yale Cancer Center and 182 patients from the American Association for Cancer Research Project GENIE database were included. In the Yale cohort, TP53 mutations were identified in 65 cases (64%), of which 23 were TP53mut/TSGmut and 42 were TP53mut/TSGwt. Although the presence of a TP53 mutation was associated with worse outcomes, the additional TSG alteration in TP53mut tumors identified a subset of patients associated with particularly aggressive disease and inferior clinical outcome in both the Yale and the GENIE cohorts. Specifically, in the Yale cohort for patients receiving first-line TKIs, those with TP53mut/TSGmut tumors had shorter progression-free survival (PFS) and overall survival (OS) than TP53mut/TSGwt (PFS: hazard ratio [HR] = 2.03, confidence interval [CI]: 1.12-3.69, p < 0.01, OS: HR = 1.58, CI: 0.82-3.04, p = 0.12) or TP53wt cases (PFS: HR 2.4, CI: 1.28-4.47, p < 0.001, OS: HR = 2.54, CI: 1.21-5.34, p < 0.005). Inferior outcomes in patients with TP53mut/TSGmut tumors were also found in those receiving osimertinib as second-line therapy. Similar findings were seen in patients in the GENIE cohort. CONCLUSIONS: Patients with TP53mut/TSGmut tumors represent a patient subgroup characterized by an aggressive disease phenotype and inferior outcomes on EGFR TKIs. This information is important for understanding the biological underpinnings of differential outcomes with TKI treatment and has implications for identifying patients who may benefit from additional therapeutic interventions beyond osimertinib monotherapy.

Prevalence and Correlates of Physical Inactivity Among Individuals with HIV During the First COVID-19 Wave: A Cross-sectional Survey.

Physical activity is associated with improved health outcomes among people with HIV (PWH). In the recent pandemic context, policies designed to mitigate COVID-19 transmission may result in an increase in sedentary lifestyle and decreased physical activity. In this study, we aimed to characterize self-reported physical activity and factors associated with physical inactivity during the first wave of the COVID-19 pandemic among a sample of PWH engaged in care. We also described whether psychological coping strategies measured by the Brief COPE differed based on physical activity levels. Among 260 surveyed PWH in two HIV clinics in the US Northeast, 28.5% (n = 74) met the criteria for being physically active according to the Centers for Disease Control and Prevention (CDC)'s physical activity guidelines. Receiving care in New Haven, CT, presence of a detectable HIV viral load, every day tobacco use, and unhealthy alcohol use were associated with physical inactivity. Problem-focused coping, emotion-focused coping, and avoidance-focused coping strategies were found to be protective against physical inactivity. In adjusted analysis, only problem-focused coping continued to be significantly associated with lower odds of reporting physical inactivity. Efforts are urgently needed to promote physical activity among PWH, including among those without problem-focused coping strategies.

RESUMEN: La actividad física se asocia con mejores resultados de salud entre las personas con VIH (PCV). En el contexto de la reciente pandemia, las políticas diseñadas para mitigar la transmisión de COVID-19 pueden resultar en un aumento del estilo de vida sedentario y una disminución de la actividad física. En este estudio, nuestro objetivo fue caracterizar la actividad física autoinformada y los factores asociados con la inactividad física durante la primera ola de la pandemia de COVID-19 entre una muestra de PCV dedicados a la atención. También describimos si las estrategias psicológicas de afrontamiento medidas por el Brief COPE diferían según los niveles de actividad física. Entre las 260 PCV encuestadas en dos clínicas de VIH en el noreste de EE. UU., el 28,5% (n = 74) cumplía con los criterios para ser físicamente activo de acuerdo con las pautas de actividad física del Centros para el Control y la Prevención de Enfermedades (CDC). Recibir atención en New Haven, CT, la presencia de una carga viral de VIH detectable, el consumo diario de tabaco, y el consumo insano de alcohol se asociaron con la inactividad física. Se encontró que el afrontamiento centrado en el problema, el afrontamiento centrado en la emoción, y las estrategias de afrontamiento centradas en la evitación, protegen contra la inactividad física. En el análisis ajustado, solo el afrontamiento centrado en el problema siguió estando significativamente asociado con menores probabilidades de informar sobre la inactividad física. Se necesitan esfuerzos urgentes para promover la actividad física entre las PCV, incluso entre aquellas que no tienen estrategias de afrontamiento centradas en el problema.

Experiences with Telemedicine for HIV Care During the COVID-19 Pandemic: A Mixed-Methods Study.

To characterize perspectives and experiences with telemedicine during the COVID-19 pandemic, we conducted a mixed-methods study in two HIV clinics in the US Northeast. Among surveyed patients with HIV (PWH) who had a telemedicine appointment (n = 205), 42.4% perceived telemedicine visits as useful during the pandemic. PWH and clinical staff identified benefits of telemedicine: (1) ability to engage and re-engage patients in care; (2) perceived patient-centeredness and flexibility; (3) opportunity to engage family and multidisciplinary care team members; and (4) opportunity to enhance telemedicine use proficiency through practice and support. Identified barriers included: (1) technical challenges; (2) privacy concerns; (3) loss of routine clinical experiences and interactions; (4) limited objective patient remote monitoring; and (5) reimbursement concerns. Efforts to optimize telemedicine for HIV care should consider strategies to improve technology support for PWH, flexible options to access care, additional platforms to allow patient remote monitoring, and appropriate billing and reimbursement methods.

RESUMEN: Para caracterizar las perspectivas sobre y las experiencias con la telemedicina durante la pandemia de COVID-19, realizamos un estudio de métodos mixtos en dos clínicas de VIH en el noreste de los Estados Unidos. Entre los pacientes con VIH (PWH) encuestados que tuvieron una cita de telemedicina (n = 205), el 42.4% percibió las visitas de telemedicina como útiles durante la pandemia. Los PWH y el personal clínico identificaron como beneficios de la telemedicina: 1) la capacidad para involucrar y reinvolucrar a los pacientes en el cuidado; 2) el cuidado centrado en el paciente y flexibilidad percibidos; 3) la oportunidad de involucrar a la familia y miembros del equipo de cuidado multidisciplinario; y 4) la oportunidad de mejorar la capacidad para usar la telemedicina a través de la práctica y el apoyo. Las barreras identificadas incluyeron: 1) retos tecnológicos; 2) preocupaciones sobre la privacidad; 3) falta de experiencias e interacciones clínicas de rutina; 4) limitada monitorización remota objetiva del paciente; y 5) preocupaciones sobre los reembolsos. Los esfuerzos para optimizar la telemedicina para el cuidado del VIH deben considerar estrategias para mejorar el soporte tecnológico para los PWH, opciones flexibles para acceder a el cuidado, plataformas adicionales que permitan el monitoreo remoto del paciente, y métodos apropiados de facturación y reembolso.

Association of Provider Perspectives on Race and Racial Health Care Disparities with Patient Perceptions of Care and Health Outcomes.

Purpose: Research suggests that providers contribute to racial disparities in health outcomes. Identifying modifiable provider perspectives that are associated with decreased racial disparities will help in the design of effective educational interventions for providers. Methods: This cross-sectional study investigated the association between primary care provider (PCP) perspectives on race and racial disparities with patient outcomes. Results: Study participants included 40 PCPs (70% White, 30% racial minority) caring for 55 patients (45% White, 55% Black) with type 2 diabetes mellitus. Associations of provider perspectives on race and racial disparities with patient variables (Interpersonal Processes of Care [IPC] Survey, which measures patient's ratings of their provider's interpersonal skills; medication adherence; glycemic control) were measured using Spearman correlation coefficients. Results suggest that Black patients of providers who reported greater skill in caring for Black patients had more positive perceptions of care in three of four IPC subdomains (Spearman correlation coefficients of -0.43, 0.44, 0.46, all with p<0.05); however, Black patients of providers who believe that racial disparities are highly prevalent had more negative perceptions of care in three of four IPC subdomains (Spearman correlation coefficients of 0.38, -0.53, -0.51, all with p<0.05). These same provider characteristics had no correlation with outcomes of medication adherence and hemoglobin A1c (HbA1c) or among White patients. Conclusion: Findings suggest that Black patients of providers who felt better equipped to take care of Black patients had a better experience. Therefore, educational interventions for providers may be most effective if they focus on skill development rather than increasing awareness about racial disparities alone.

Racial differences in patient perception of interactions with providers are associated with health outcomes in type II diabetes.

OBJECTIVES: Examine the association of patient perceptions of care with hemoglobin A1c (HbA1c), medication adherence, and missed appointments in non-Hispanic Black (NHB) and White (NHW) patients with type 2 diabetes (T2DM). METHODS: We used linear and logistic regression models to analyze the association of the Interpersonal Processes of Care survey (IPC) with HbA1c, medication adherence, and missed appointments. We then examined how these associations differed by race. RESULTS: There was no overall association between IPC subdomains and HbA1c in our sample (N = 221). NHB patients perceiving their provider always explained results and medications had a HbA1c on average 0.59 (-1.13, -0.04; p = 0.04) points lower than those perceiving their provider sometimes explained results and medications. No effect was observed in NHWs. Never perceiving disrespect from office staff was associated with an average 0.67 (-1.1, -0.24; p = 0.002) point improvement in medication adherence for all patients. Never perceiving discrimination from providers was associated with a 0.44 (-0.63, -0.25; p < 0.0001) decrease in the probability of missing an appointment for NHB patients. CONCLUSIONS: These results demonstrate that particular aspects of communication in the patient-provider interaction may contribute to racial disparities in T2DM. PRACTICE IMPLICATIONS: Communication training for both providers and staff may reduce disparities in T2DM.

Antarcticimonas flava gen. nov., sp. nov., isolated from Antarctic coastal seawater.

A marine bacterium, designated IMCC3175(T), was isolated from a seawater sample collected off the Antarctic coast. The strain was Gram-negative, obligately aerobic, carotenoid pigment-containing, and rod-shaped bacterium that divided by binary fission. As determined by 16S rRNA gene sequence comparisons, the most closely related genera were Formosa (92.9 approximately 93.3%), Bizionia (91.6 approximately 93.2%), Gaetbulibacter (91.5 approximately 92.8%), Sediminibacter (92.7%), Yeosuana (92.6%), Subsaximicrobium (92.1 approximately 92.2%), and Gillisia (89.5 approximately 92.2%). Phylogenese analysis based on 16S rRNA gene sequences showed that the strain formed a monophyletic clade together with the genera Sediminibacter and Subsaximicrobium but represented an independent phyletic line in this clade of the family Flavobacteriaceae. The DNA G+C content of the strain was 37.3 mol%. The major respiratory quinone was MK-6 and the predominant cellular fatty acids were C(16:1) omega7c and/or iso-C(15:0) 2-OH (12.8%), anteiso-C(15:0) (9.4%), and iso-C(16:1) (9.4%). Low 16S rRNA gene sequence similarity, formation of a distinct phylogenetic branch, and several phenotypic characteristics, including a narrow range of temperature and salinity for growth, differentiated strain IMCC3175(T) from other related genera in the family Flavobacteriaceae. Therefore the name Antarcticimonas flava gen. nov., sp. nov. is proposed, with strain IMCC3175(T) (=KCCM 42713(T) =NBRC 103398(T)) as the type strain.