RESUMO
The AP-1 transcription factor (TF) dimer contributes to many biological processes and environmental responses. AP-1 can be composed of many interchangeable subunits. Unambiguously determining the binding locations of these subunits in the human genome is challenging because of variable antibody specificity and affinity. Here, we definitively establish the genome-wide binding patterns of five AP-1 subunits by using CRISPR to introduce a common antibody tag on each subunit. We find limited evidence for strong dimerization preferences between subunits at steady state and find that, under a stimulus, dimerization patterns reflect changes in the transcriptome. Further, our analysis suggests that canonical AP-1 motifs indiscriminately recruit all AP-1 subunits to genomic sites, which we term AP-1 hotspots. We find that AP-1 hotspots are predictive of cell type-specific gene expression and of genomic responses to glucocorticoid signaling (more so than super-enhancers) and are significantly enriched in disease-associated genetic variants. Together, these results support a model where promiscuous binding of many AP-1 subunits to the same genomic location play a key role in regulating cell type-specific gene expression and environmental responses.
Assuntos
Elementos Facilitadores Genéticos , Regulação da Expressão Gênica , Fator de Transcrição AP-1/metabolismo , Transcrição Gênica , Elementos Facilitadores Genéticos/genética , Humanos , Transdução de SinaisRESUMO
PURPOSE: Opportunities exist for patients with metastatic breast cancer (MBC) to engage in shared decision-making (SDM). Presenting patient-reported data, including patient treatment preferences, to oncologists before or during a treatment plan decision may improve patient engagement in treatment decisions. METHODS: This randomized controlled trial evaluated the standard-of-care treatment planning process vs. a novel treatment planning process focused on SDM, which included oncologist review of patient-reported treatment preferences, prior to or during treatment decisions among women with MBC. The primary outcome was patient perception of shared decision-making. Secondary outcomes included patient activation, treatment satisfaction, physician perception of treatment decision-making, and use of treatment plans. RESULTS: Among the 109 evaluable patients from December 2018 to June 2022, 28% were Black and 12% lived in a highly disadvantaged neighborhood. Although not reaching statistical significance, patients in the intervention arm perceived SDM more often than patients in the control arm (63% vs. 59%; Cramer's V = 0.05; OR 1.19; 95% CI 0.55-2.57). Among patients in the intervention arm, 31% were at the highest level of patient activation compared to 19% of those in the control arm (V = 0.18). In 82% of decisions, the oncologist agreed that the patient-reported data helped them engage in SDM. In 45% of decision, they reported changing management due to patient-reported data. CONCLUSIONS: Oncologist engagement in the treatment planning process, with oncologist review of patient-reported data, is a promising approach to improve patient participation in treatment decisions which should be tested in larger studies. TRIAL REGISTRATION: NCT03806738.
Assuntos
Neoplasias da Mama , Tomada de Decisão Compartilhada , Participação do Paciente , Humanos , Feminino , Neoplasias da Mama/psicologia , Neoplasias da Mama/terapia , Pessoa de Meia-Idade , Idoso , Relações Médico-Paciente , Preferência do Paciente , Adulto , Planejamento de Assistência ao PacienteRESUMO
CRISPR-Cas9 technologies have dramatically increased the ease of targeting DNA sequences in the genomes of living systems. The fusion of chromatin-modifying domains to nuclease-deactivated Cas9 (dCas9) has enabled targeted epigenome editing in both cultured cells and animal models. However, delivering large dCas9 fusion proteins to target cells and tissues is an obstacle to the widespread adoption of these tools for in vivo studies. Here, we describe the generation and characterization of two conditional transgenic mouse lines for epigenome editing, Rosa26:LSL-dCas9-p300 for gene activation and Rosa26:LSL-dCas9-KRAB for gene repression. By targeting the guide RNAs to transcriptional start sites or distal enhancer elements, we demonstrate regulation of target genes and corresponding changes to epigenetic states and downstream phenotypes in the brain and liver in vivo, and in T cells and fibroblasts ex vivo. These mouse lines are convenient and valuable tools for facile, temporally controlled, and tissue-restricted epigenome editing and manipulation of gene expression in vivo.
Assuntos
Sistemas CRISPR-Cas , Epigênese Genética , Epigenoma , Edição de Genes/métodos , Regulação da Expressão Gênica , Animais , Encéfalo/metabolismo , Feminino , Fibroblastos/metabolismo , Humanos , Fígado/metabolismo , Masculino , Camundongos , Camundongos Transgênicos , Linfócitos T/metabolismoRESUMO
BACKGROUND: Cancer registry-based "primary payer at diagnosis" (PPDx) data are commonly used to evaluate the effect of insurance on cancer care outcomes, yet little is known about how well they capture Medicaid or Medicare enrollment. METHODS: We linked the National Cancer Institute's Surveillance, Epidemiology, and End Results registry data to monthly Centers for Medicare and Medicaid Services (CMS) Medicaid and Medicare enrollment records, state-year Medicaid policy, and managed care enrollment. We selected adults aged 19-64 years diagnosed between 2007 and 2011. We used bivariate analyses to compare PPDx to CMS enrollment at diagnosis month and assessed underreporting rates by patient characteristics and state-year policy. RESULTS: PPDx reported 7.8% Medicare and 10.1% Medicaid, whereas CMS enrollment indicated 5.5% Medicare, 10.4% Medicaid, and 3.4% dual Medicare-Medicaid (N = 896,031). Positive predictive values for PPDx assignment to Medicaid and Medicare were 65.3% and 75.4%, with false negative rates of 52.0% and 33.8%, respectively. Medicaid underreporting was higher in low (56.5%) versus high (50.8%) poverty areas, for males (56.1%) versus females (48.9%), for Medicaid poverty expansion or waiver enrolled (63.8%) versus cash assistance-related eligibility (47.3%), and in states with large managed care enrollment (all P < 0.001). If Medicaid and Medicare enrollment data were used to edit PPDx, 12.0% of persons would switch primary payer assignment. CONCLUSIONS: Registry-reported PPDx fails to fully capture Medicaid and Medicare enrollment, which may result in biased estimates of insurance-related policy impacts. Enhancement with objective enrollment data could reduce measurement error and bias in estimates necessary to support policy assessment.
Assuntos
Medicare , Neoplasias , Masculino , Adulto , Feminino , Humanos , Idoso , Estados Unidos , Medicaid , Sistema de Registros , Programas de Assistência Gerenciada , Políticas , Neoplasias/epidemiologiaRESUMO
OBJECTIVES: To evaluate existing distress screening to identify patients with financial hardship (FH) compared to dedicated FH screening and assess patient attitudes toward FH screening. METHODS: We screened gynecologic cancer patients starting a new line of therapy. Existing screening included: (1) Moderate/severe distress defined as Distress Thermometer score ≥ 4, (2) practical concerns identified from Problem Checklist, and (3) a single question assessing trouble paying for medications. FH screening included: (1) Comprehensive Score for Financial Toxicity (COST) tool and (2) 10-item Financial Needs Checklist to guide referrals. FH was defined as COST score < 26. We calculated sensitivity (patients with moderate/severe distress + FH over total patients with FH) and specificity (patients with no/mild distress + no FH over total patients with no FH) to assess the extent distress screening could capture FH. Surveys and exit interviews assessed patient perspectives toward screening. RESULTS: Of 364 patients screened for distress, average age was 62 years, 25% were Black, 45% were Medicare beneficiaries, 32% had moderate/severe distress, 15% reported ≥1 practical concern, and 0 reported trouble paying for medications. Most (n = 357, 98%) patients also completed FH screening: of them, 24% screened positive for FH, 32% reported ≥1 financial need. Distress screening had 57% sensitivity and 77% specificity for FH. Based on 79 surveys and 43 exit interviews, FH screening was acceptable with feedback to improve the timing and setting of screening. CONCLUSIONS: Dedicated FH screening was feasible and acceptable, but sensitivity was low. Importantly, 40% of women with FH would not have been identified with distress screening alone.
Assuntos
Estresse Financeiro , Neoplasias dos Genitais Femininos , Humanos , Feminino , Neoplasias dos Genitais Femininos/diagnóstico , Neoplasias dos Genitais Femininos/economia , Neoplasias dos Genitais Femininos/psicologia , Pessoa de Meia-Idade , Estresse Financeiro/psicologia , Estresse Financeiro/diagnóstico , Idoso , Angústia Psicológica , Programas de Rastreamento/economia , Programas de Rastreamento/métodos , Inquéritos e QuestionáriosRESUMO
OBJECTIVE: Caregivers support individuals undergoing cancer treatment by assisting with activities, managing care, navigating healthcare systems, and communicating with care teams. We explored the quality and quantity of caregiver participation during recorded decision-making clinical appointments in women with metastatic breast cancer. METHODS: This was a convergent parallel mixed methods study that utilized qualitative and quantitative data collection and analysis. Caregiver participation quality was operationalized using a summative thematic content analysis to identify and sum caregiver actions performed during appointments. Performance of a greater number of actions was considered greater quality of participation. Caregiver participation quantity was measured by calculating the proportion of speaking time. Participation quality and quantity were compared to patient activation, assessed using the Patient Activation Measure 1-month post decision-making appointment. RESULTS: Fifty-three clinical encounters between patients with MBC, their caregivers, and oncologists were recorded. Identified caregiver actions included: General Support; Management of Treatment or Medication; Treatment History; Decision-Making; Insurance or Money; Pharmacy; Scheduling; Travel Concerns; General Cancer Understanding; Patient Specific Cancer Understanding; Caregiver-Initiated or Emphasis on Symptom Severity; and Caregiver Back-Up of Patient Symptom Description. Caregivers averaged 5 actions (SD 3): 48% of patient's caregivers had low quality (< 5 actions) and 52% had high quality (> 6 actions) participation. Regarding quantity, caregivers spoke on average for 4% of the encounter, with 60% of caregivers speaking less than 4% of the encounter (low quantity) and 40% of caregivers speaking more than 4% (high quantity). Greater quality and quantity of caregiver participation was associated with greater patient activation. CONCLUSIONS: Caregivers perform a variety of actions during oncological decision-making visits aiding both patient and provider. Greater participation in terms of quantity and quality by the caregiver was associated with greater patient activism, indicating a need for better integration of the caregiver in clinical decision-making environments.
Assuntos
Neoplasias da Mama , Cuidadores , Tomada de Decisões , Participação do Paciente , Humanos , Feminino , Cuidadores/psicologia , Neoplasias da Mama/terapia , Pessoa de Meia-Idade , Participação do Paciente/estatística & dados numéricos , Idoso , Adulto , Metástase Neoplásica , Pesquisa QualitativaRESUMO
OBJECTIVE: To examine the association between rehabilitation utilization within 12 months of breast cancer diagnosis and out-of-pocket costs in the second year (12 - 24 months following diagnosis). DESIGN: Secondary analysis of the 2009-2019 Surveillance, Epidemiology and End Results-Medicare linked database. Individuals who received rehabilitation services were propensity-score matched to individuals who did not receive services. Overall and health care service-specific models were examined using generalized linear models with a gamma distribution. SETTING: Inpatient and outpatient medical facilities in the United States PARTICIPANTS: : 35,212 individuals diagnosed with non-metastatic breast cancer and were continuously enrolled in Medicare Fee-For Service (parts A, B, and D) in the 12 months prior to and 24 months post- diagnosis. INTERVENTION: Not applicable MAIN OUTCOME MEASURES: : Individual cost responsibility, a proxy for out-of-pocket costs, which was defined as deductibles, coinsurance, and copayments during the second year following diagnosis (12 - 24 months post- diagnosis). RESULTS: The mean individual cost responsibility was higher in individuals who utilized rehabilitation compared to those who did not ($4,013 vs. $3,783), although it was not a clinically meaningful difference (d=0.06). Individuals who received rehabilitative services had significantly higher costs attributed to individual provider care ($1,634 vs. $1,476), institutional outpatient costs ($886 vs. $812), and prescription drugs ($959 vs. $906), and significantly lower costs attributed to institutional inpatient costs ($455 vs. $504), and durable medical equipment ($81 vs. $86). CONCLUSIONS: Older adults with breast cancer who received rehabilitation services had higher cost responsibility during the second year following diagnosis compared to those who did not. Future work is needed to examine the relationship between rehabilitation and out-of-pocket costs across longer periods of time and in conjunction with perceived benefit.
RESUMO
BACKGROUND: Maternal health outcomes in the United States raises concern due to elevated rates of pregnancy-related deaths compared to other developed and underdeveloped countries. This scoping review explores relationships between social determinants of health (SDOH), postpartum visit attendance, and pregnancy-related deaths. METHODS: Utilizing the Arksey and O'Malley framework and PRISMA-Scr guidelines, a systematic review was conducted to identify pertinent literature. RESULTS: Eight studies were analyzed, providing insights into SDOH, postpartum visits, and pregnancy-related deaths. The findings highlight healthcare access/quality, economic stability, education, and social/community context as influential in postpartum care utilization. Health insurance emerges a key factor for postpartum attendance. In addition, disparities in geographic access to maternity care services were linked to pregnancy-related deaths. Social contextual factors, such as marital status and social support, exhibited varying associations with postpartum visit attendance. CONCLUSION: While the analyzed studies provided valuable insight, there remains a gap in the literature examining all three key elements: SDOH, postpartum visit attendance, and pregnancy-related deaths. In conclusion, this scoping review highlights the vital role of addressing social determinants in improving maternal health outcomes. Further research is necessary to better inform interventions to reduce pregnancy-related deaths.
Assuntos
Mortalidade Materna , Cuidado Pós-Natal , Determinantes Sociais da Saúde , Humanos , Feminino , Gravidez , Estados Unidos , Acessibilidade aos Serviços de Saúde , Serviços de Saúde Materna , Adulto , Período Pós-PartoRESUMO
BACKGROUND: Data on financial hardship, an "adverse event" in individuals with cancer, are needed to inform policy and supportive care interventions and reduce adverse economic outcomes. METHODS: Lay navigator-led financial hardship screening was piloted among University of Alabama at Birmingham oncology patients initiating treatment in October 2020. Financial hardship screening, including reported financial distress and difficulty, was added to a standard-of-care treatment planning survey. Screening feasibility and completion and proportions of reported financial distress and difficulty were calculated overall and by patient race and rurality. The risk of financial distress by patient sociodemographics was estimated. RESULTS: Patients who completed a treatment planning survey (N=2741) were 18% Black, Indigenous, or persons of color (BIPOC) and 16% rural dwelling. The majority of patients completed financial hardship screening (90%), surpassing the target feasibility completion rate of 75%. The screening revealed 34% of patients were experiencing financial distress, including 49% of BIPOC and 30% of White patients. Adjusted models revealed BIPOC patients had a 48% higher risk of financial distress compared with those who were White (risk ratio 1.48, 95% CI, 1.31-1.66). Large differences in reported financial difficulties were seen comparing patients who were BIPOC and White (utilities: 33% vs. 10%, upfront medical payments: 44% vs. 23%, transportation: 28% vs. 12%, respectively). CONCLUSIONS: The collection of patient-reported financial hardship data via routine clinical care was feasible and identified racial inequities at treatment initiation. Efforts to collect patient economic data should support the design, implementation, and evaluation of patient-centered interventions to improve equity and reduce the impact of financial hardship.
Assuntos
Estresse Financeiro , Neoplasias , Humanos , Detecção Precoce de Câncer , Neoplasias/diagnóstico , Neoplasias/terapia , Inquéritos e QuestionáriosRESUMO
BACKGROUND: People experiencing financial burden are underrepresented in clinical trials. OBJECTIVE: Describe the prevalence of cost-related considerations influential to trial participation and their associations with person-level characteristics. DESIGN: This cross-sectional study used and assessed how three cost-related considerations would influence the decision to participate in a hypothetical clinical trial. PARTICIPANTS: A total of 3682 US adult respondents to the Health Information National Trends Survey MAIN MEASURES: Survey-weighted multivariable logistic regression estimated associations between respondent characteristics and odds of reporting cost-related considerations as very influential to participation. KEY RESULTS: Among 3682 respondents, median age was 48 (IQR 33-61). Most were non-Hispanic White (60%), living comfortably or getting by on their income (74%), with ≥ 1 medical condition (61%). Over half (55%) of respondents reported at least one cost-related consideration as very influential to trial participation, including if usual care was not covered by insurance (reported by 42%), payment for participation (24%), or support for participation (24%). Respondents who were younger (18-34 vs. ≥ 75, adjusted odds ratio [aOR] 4.3, 95% CI 2.3-8.1), more educated (high school vs. Assuntos
Renda
, Adulto
, Humanos
, Pessoa de Meia-Idade
, Estudos Transversais
, Inquéritos e Questionários
RESUMO
Among the pathological events associated with the dopaminergic neurodegeneration characteristic of Parkinson's disease (PD) are the accumulation of toxic forms of α-synuclein and microglial activation associated with neuroinflammation. Although numerous other processes may participate in the pathogenesis of PD, the two factors mentioned above may play critical roles in the initiation and progression of dopamine neuron degeneration in PD. In this study, we employed a slowly progressing model of PD using adeno-associated virus-mediated expression of human A53T α-synuclein into the substantia nigra on one side of the brain and examined the microglial response in the striatum on the injected side compared to the non-injected (control) side. We further examined the extent to which administration of the neuroprotective ganglioside GM1 influenced α-synuclein-induced glial responses. Changes in a number of microglial morphological measures (i.e., process length, number of endpoints, fractal dimension, lacunarity, density, and cell perimeter) were indicative of the presence of activated microglial and an inflammatory response on the injected side of the brain, compared to the control side. In GM1-treated animals, no significant differences in microglial morphology were observed between the injected and control striata. Follow-up studies showed that mRNA expression for several inflammation-related genes was increased on the A53T α-synuclein injected side vs. the non-injected side in saline-treated animals and that such changes were not observed in GM1-treated animals. These data show that inhibition of microglial activation and potentially damaging neuroinflammation by GM1 ganglioside administration may be among the many factors that contribute to the neuroprotective effects of GM1 in this model and possibly in human PD.
Assuntos
Gangliosídeo G(M1) , Microglia , Doença de Parkinson , alfa-Sinucleína , Animais , Modelos Animais de Doenças , Dopamina/metabolismo , Gangliosídeo G(M1)/farmacologia , Inflamação/tratamento farmacológico , Inflamação/metabolismo , Microglia/efeitos dos fármacos , Microglia/metabolismo , Microglia/patologia , Doença de Parkinson/tratamento farmacológico , Doença de Parkinson/metabolismo , Ratos , Substância Negra/efeitos dos fármacos , Substância Negra/metabolismo , Substância Negra/patologia , alfa-Sinucleína/genética , alfa-Sinucleína/metabolismoRESUMO
PURPOSE: Healthcare discrimination has been associated with health disparities including lower cancer screenings, higher medical mistrust, and strained patient-provider relationships. Our study sought to understand patient-reported discrimination among cancer survivors with limited resources living in the United States. DESIGN AND METHODS: We used cross-sectional survey data distributed by the Patient Advocate Foundation (PAF) in 12/2020 and 07/2021. Respondents reported source and reason of healthcare discrimination. Age, sex, race and ethnicity, annual household income, Rural-Urban Commuting Area (RUCA), Area Deprivation Index (ADI), employment status, cancer type, and number of comorbidities were independent variables of interest. The association between these variables and patient-reported healthcare discrimination was estimated using risk ratios (RRs) and 95% confidence intervals (CIs) from a multivariable modified Poisson regression model with robust standard errors. FINDINGS: A total of 587 cancer survivors were included in our analysis. Most respondents were female (72%) and aged ≥56 (62%); while 33% were Black, Indigenous, or Person of Color. Overall, 23% reported receipt of discrimination, with the majority reporting doctor, nurse, or healthcare provider as the source (58%). Most common reasons for discrimination included disease status (42%), income/ability to pay (36%), and race and ethnicity (17%). In the adjusted model, retired survivors were 62% less likely to report discrimination compared to those employed (RR 0.38; 95% CI 0.23-0.64). Additionally, survivors with ≥3 comorbidities were 86% more likely to report discrimination compared to those survivors with no non-cancer comorbidities (RR 1.86; 95% CI 1.26-2.72). IMPLICATIONS: Cancer survivors with limited resources reported substantial discrimination most often from a healthcare provider and most commonly for disease status and income. Discrimination should be mitigated to provide equitable and high-quality cancer care.
Assuntos
Sobreviventes de Câncer , Neoplasias , Humanos , Feminino , Estados Unidos , Masculino , Estudos Transversais , Confiança , Etnicidade , Neoplasias/terapia , Medidas de Resultados Relatados pelo PacienteRESUMO
BACKGROUND: Clinical trials offer novel treatments, which are essential to high quality cancer care. Patients living in rural areas are often underrepresented in clinical trials due to several factors. This study evaluated the association between rurality and interest in clinical trial participation, change in interest, and treatment decision-making style preference. METHODS: This cohort study included patients with cancer receiving oncology care at the University of Alabama at Birmingham from 2017 to 2019. Associations between treatment decision-making preference and the interaction between rurality and area deprivation were analyzed using multinomial logistic regression. Initial interest in clinical trial participation and change in interest were analyzed using modified Poisson regressions with robust standard errors. Initial interest model was stratified by Area Deprivation Index (ADI; higher vs. lower disadvantaged). RESULTS: In adjusted models, patients in rural versus urban areas had similar initial interest in clinical trials, both those in higher (40% vs. 50%) and lower disadvantaged settings (54% vs. 62%). Additionally, rural versus urban patients had similar change of clinical trial interest for both those who changed from uninterested-to-interested (31% vs. 26%) and interested-to-uninterested (47% vs. 42%). CONCLUSION: This study compares the interest in clinical trial participation among patients living in rural and urban settings. Lack of interest may be secondary to barriers that patients in rural areas face (e.g., transportation, financial, access). Most rural patients prefer a shared treatment decision-making style, which should be considered when identifying interventions to increase enrollment of underserved rural patients in clinical trials.
Assuntos
Ensaios Clínicos como Assunto , Neoplasias , Participação do Paciente , Humanos , Estudos de Coortes , Geografia , Neoplasias/terapia , População Rural , Populações VulneráveisRESUMO
Human Fibroblast Growth Factor 19 (FGF19) and mouse ortholog Fgf15 play similar roles in liver regeneration and metabolism via the activation of Fgfr4/b-klotho (Klb). Monomeric FGF19 and dimeric Fgf15 are both necessary for liver regeneration and proper bile acid (BA) metabolism. FGF19 elicits stronger effects than Fgf15 on glucose and fatty acid metabolism and only FGF19 induces hepatocellular carcinoma (HCC). However, inhibiting FGF19/FGFR4 signaling in HCC patients is associated with toxicity due to elevated BA levels. Here, we examine the structure/function relationship in Fgf15/FGF19 to better understand the molecular basis for their distinct functions. We demonstrate that FGF19 is a more effective activator of Fgfr4 and of downstream signaling (Erk, Plcg1) than Fgf15. Furthermore, we use site-directed mutagenesis to show that the presence or absence of an unpaired cysteine in Fgf15/19 modulates ligand structure and determines the ability of these molecules to induce hepatocyte proliferation, with monomers being more potent activators. Consistent with these findings, an engineered dimeric variant of FGF19 is less effective than wild-type FGF19 at inducing liver growth in cooperation with the Wnt-enhancer RSPO3. In contrast to effects on proliferation, monomeric and dimeric ligands equally inhibited the expression of Cyp7a1, the enzyme catalyzing the rate limiting step in BA production. Thus, structure and function of Fgf15/FGF19 are intricately linked, explaining why FGF19, but not Fgf15, induces liver tumorigenesis. Our data provide insight into FGF19/FGFR4 signaling and may inform strategies to target this pathway while limiting on-target toxicity due to dysregulation of BA production or induction of hepatocyte proliferation.
Assuntos
Proliferação de Células , Fatores de Crescimento de Fibroblastos/metabolismo , Hepatócitos/metabolismo , Multimerização Proteica , Transdução de Sinais , Motivos de Aminoácidos , Animais , Colesterol 7-alfa-Hidroxilase/metabolismo , Feminino , Fatores de Crescimento de Fibroblastos/química , Fatores de Crescimento de Fibroblastos/genética , Células HEK293 , Humanos , Masculino , Camundongos , Mutação , Receptor Tipo 4 de Fator de Crescimento de Fibroblastos/metabolismo , Trombospondinas/metabolismoRESUMO
PURPOSE: Telemedicine use during the COVID-19 pandemic among financially distressed patients with cancer, with respect to the determinants of adoption and patterns of utilization, has yet to be delineated. We sought to systematically characterize telemedicine utilization in financially distressed patients with cancer during the COVID-19 pandemic. METHODS: We conducted a cross-sectional analysis of nationwide survey data assessing telemedicine use in patients with cancer during the COVID-19 pandemic collected by Patient Advocate Foundation (PAF) in December 2020. Patients were characterized as financially distressed by self-reporting limited financial resources to manage out-of-pocket costs, psychological distress, and/or adaptive coping behaviors. Primary study outcome was telemedicine utilization during the pandemic. Secondary outcomes were telemedicine utilization volume and modality preferences. Multivariable and Poisson regression analyses were used to identify factors associated with telemedicine use. RESULTS: A convenience sample of 627 patients with cancer responded to the PAF survey. Telemedicine adoption during the pandemic was reported by 67% of patients, with most (63%) preferring video visits. Younger age (19-35 age compared to ≥ 75 age) (OR, 6.07; 95% CI, 1.47-25.1) and more comorbidities (≥ 3 comorbidities compared to cancer only) (OR, 1.79; 95% CI, 1.13-2.65) were factors associated with telemedicine adoption. Younger age (19-35 years) (incidence rate ratios [IRR], 1.78; 95% CI, 24-115%) and higher comorbidities (≥ 3) (IRR; 1.36; 95% CI, 20-55%) were factors associated with higher utilization volume. As area deprivation index increased by 10 units, the number of visits decreased by 3% (IRR 1.03, 95% CI, 1.03-1.05). CONCLUSIONS: The rapid adoption of telemedicine may exacerbate existing inequities, particularly among vulnerable financially distressed patients with cancer. Policy-level interventions are needed for the equitable and efficient provision of this service.
Assuntos
COVID-19 , Neoplasias , Telemedicina , Adulto , Estudos Transversais , Humanos , Neoplasias/terapia , Pandemias , Telemedicina/métodos , Adulto JovemRESUMO
BACKGROUND: The objective of the current study was to understand treatment preferences and their association with financial toxicity in Patient Advocate Foundation clients with breast cancer. METHODS: This choice-based conjoint analysis used data from a nationwide sample of women with breast cancer who received assistance from the Patient Advocate Foundation. Choice sets created from 13 attributes of 3 levels each elicited patient preferences and trade-offs. Latent class analysis segmented respondents into distinct preference archetypes. The Comprehensive Score for Financial Toxicity (COST) tool captured financial toxicity. Adjusted generalized linear models estimated COST score differences by preference archetype. RESULTS: Of 220 respondents (for a response rate of 10%), the median age was 58 years (interquartile range, 49-66 years); 28% of respondents were Black, indigenous, or people of color; and approximately 60% had household incomes <$40,000. The majority of respondents were diagnosed with early-stage cancer (91%), 38% had recurrent disease, and 61% were receiving treatment. Treatment choice was most affected by preferences related to affordability and impact on activities of daily living. Two distinct treatment preference archetypes emerged. The "cost-prioritizing group" (75% of respondents) was most concerned about affordability, impact on activities of daily living, and burdening care partners. The "functional independence-prioritizing group" (25% of respondents) was most concerned about their ability to work, physical side effects, and interference with life events. COST scores were found to be similar between the archetypes in adjusted models (cost-prioritizing group COST score, 12 [95% confidence interval, 9-14]; and functional independence-prioritizing COST score, 11 [95% confidence interval, 9-13]). CONCLUSIONS: Patients with breast cancer prioritized affordability or maintaining functional independence when making treatment decisions. Because of this variability, preference evaluation during treatment decision making could optimize patients' treatment experiences.
Assuntos
Neoplasias da Mama/terapia , Preferência do Paciente , Atividades Cotidianas , Idoso , Neoplasias da Mama/economia , Efeitos Psicossociais da Doença , Estudos Transversais , Feminino , Humanos , Pessoa de Meia-IdadeRESUMO
Tumor stem cells and malignant multicellular networks have been separately implicated in the therapeutic resistance of glioblastoma multiforme (GBM), the most aggressive type of brain cancer in adults. Here, we show that small-molecule inhibition of RHO-associated serine/threonine kinase proteins (ROCKi) significantly promoted the outgrowth of neurite-like cell projections in cultures of heterogeneous patient-derived GBM stem-like cells. These projections formed de novo-induced cellular network (iNet) 'webs', which regressed after withdrawal of ROCKi. Connected cells within the iNet web exhibited long range Ca2+ signal transmission, and significant lysosomal and mitochondrial trafficking. In contrast to their less-connected vehicle control counterparts, iNet cells remained viable and proliferative after high-dose radiation. These findings demonstrate a link between ROCKi-regulated cell projection dynamics and the formation of radiation-resistant multicellular networks. Our study identifies means to reversibly induce iNet webs ex vivo, and may thereby accelerate future studies into the biology of GBM cellular networks.
Assuntos
Glioblastoma/metabolismo , Células-Tronco Neoplásicas/metabolismo , Neuritos/metabolismo , Sinalização do Cálcio/fisiologia , Linhagem Celular Tumoral , Movimento Celular/fisiologia , Humanos , Immunoblotting , Lisossomos/metabolismo , Mitocôndrias/metabolismo , Crescimento Neuronal/fisiologia , Fenótipo , Proteínas Serina-Treonina Quinases/metabolismoRESUMO
PURPOSE: The extent to which evidence-based treatments are applied to populations not well represented in early stage breast cancer (EBC) trials remains unknown. This study evaluated treatment intensity for patients traditionally well represented, underrepresented, and unrepresented in clinical trials. METHODS: This retrospective cohort study used real-world data to evaluate the intensity (high or low) of EBC chemotherapy by patient characteristics (age, race and ethnicity, presence of comorbidity) denoting clinical trial representation status (well represented, underrepresented, unrepresented) for patients diagnosed from 2011 to 2020. Odds ratios (OR) from a logistic regression model was used to evaluate the association between receipt of high-intensity chemotherapy and clinical trial representation status characteristics adjusting for cancer stage and subtype. RESULTS: Of 970 patients with EBC, 41% were characterized as well represented, 45% as underrepresented, and 13% as unrepresented in clinical trials. In adjusted models, patients aged ≥ 70 versus 45-69 had lower odds of receiving a high-intensity treatment (OR 0.40, 95% CI 0.26-0.60), while those aged < 45 versus 45-69 had higher odds of receiving high-intensity treatment (OR 1.82, 95% CI 1.10-3.01). In predicted estimates, the proportion of patients receiving a high-intensity treatment was 87% for patients aged < 45, 79% for patients aged 45-69, and 60% for patients aged ≥ 70. CONCLUSION: 59% of the EBC population is not well represented in clinical trials. Age was associated with differential treatment intensity. Widening clinical trial eligibility criteria should be considered to better understand survival outcomes, toxicity effects, and ultimately make evidence-based treatment decisions using a more diverse sample.
Assuntos
Neoplasias da Mama , Ensaios Clínicos como Assunto , Idoso , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/patologia , Ensaios Clínicos como Assunto/estatística & dados numéricos , Feminino , Humanos , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Estudos RetrospectivosRESUMO
OBJECTIVE: Shared decision-making (SDM) occurs when physicians and patients jointly select treatment that aligns with patient care goals. Incorporating patient preferences into the decision-making process is integral to successful decision-making. This study explores factors influencing treatment selection in older patients with early-stage breast cancer (EBC). METHODS: This qualitative study included women age ≥65 years with EBC. To understand role preferences, patients completed the Control Preferences Scale. Semi-structured interviews were conducted to explore patients' treatment selection rationale. Interview transcripts were analyzed using a constant comparative method identifying major themes related to treatment selection. RESULTS: Of 33 patients, the majority (48%) desired shared responsibility in treatment decision-making. Interviews revealed that EBC treatment incorporated three domains: Intrinsic and extrinsic influences, clinical characteristics, and patient values. Patients considered 19 treatment selection themes, the most prioritized including physician trust and physical side effects. CONCLUSIONS: Because preferences and approach to treatment selection varied widely in this sample of older, EBC patients, more research is needed to determine best practices for preference incorporation to optimize SDM at the time of treatment decisions.
Assuntos
Neoplasias da Mama/terapia , Tomada de Decisão Compartilhada , Preferência do Paciente/psicologia , Relações Médico-Paciente , Idoso , Neoplasias da Mama/patologia , Feminino , Humanos , Estadiamento de Neoplasias , Planejamento de Assistência ao Paciente , Pesquisa QualitativaRESUMO
The common fern, bracken (Pteridium aquilinum), is well known for its toxic effects on livestock due principally to the carcinogenic constituent ptaquiloside ( 1: ), although other toxins are present including the cyanogenic glycoside, prunasin ( 2: ). Here, we report an improved and relatively "green" process for the isolation of 1: and 2: from fresh bracken fronds and the evaluation of 1: for cytotoxicity against several cancer cell lines. The results indicate that 1: displays selective toxicity against cancer cells relative to noncancer retinal epithelial cells, and the improved method for the isolation of 1: is expected to facilitate further exploration of its pharmacological properties.