Financial burden among metastatic breast cancer patients: a qualitative inquiry of costs, financial assistance, health insurance, and financial coping behaviors.

PURPOSE: Metastatic breast cancer (MBC) patients often face substantial financial burden due to prolonged and expensive therapy. However, in-depth experiences of financial burden among MBC patients are not well understood. METHODS: Qualitative interviews were conducted to describe the experiences of financial burden for MBC patients, focusing on the drivers of financial burden, their experience using their health insurance, accessing financial assistance, and any resulting cost-coping behaviors. Interviews were transcribed and qualitatively analyzed using a descriptive phenomenological approach to thematic analysis. RESULTS: A total of n = 11 MBC patients or caregiver representatives participated in the study. MBC patients were on average 50.2 years of age (range: 28-65) and 72.7% non-Hispanic White. MBC patients were diagnosed as metastatic an average of 3.1 years (range: 1-9) before participating in the study. Qualitative analysis resulted in four themes including (1) causes of financial burden, (2) financial assistance mechanisms, (3) health insurance and financial burden, and (4) cost-coping behaviors. Both medical and non-medical costs drove financial burden among participants. All participants reported challenges navigating their health insurance and applying for financial assistance. Regardless of gaining access to assistance, financial burden persisted for nearly all patients and resulted in cost-coping behaviors. CONCLUSION: Our findings suggest that current systems for health insurance and financial assistance are complex and difficult to meet patient needs. Even when MBC patients accessed assistance, excess financial burden persisted necessitating use of financial coping-behaviors such as altering medication use, maintaining employment, and taking on debt.

Assessing the pre-implementation context for financial navigation in rural and non-rural oncology clinics.

Background: Financial navigation (FN) is an evidence-based intervention designed to address financial toxicity for cancer patients. FN's success depends on organizations' readiness to implement and other factors that may hinder or support implementation. Tailored implementation strategies can support practice change but must be matched to the implementation context. We assessed perceptions of readiness and perceived barriers and facilitators to successful implementation among staff at nine cancer care organizations (5 rural, 4 non-rural) recruited to participate in the scale-up of a FN intervention. To understand differences in the pre-implementation context and inform modifications to implementation strategies, we compared findings between rural and non-rural organizations. Methods: We conducted surveys (n = 78) and in-depth interviews (n = 73) with staff at each organization. We assessed perceptions of readiness using the Organizational Readiness for Implementing Change (ORIC) scale. In-depth interviews elicited perceived barriers and facilitators to implementing FN in each context. We used descriptive statistics to analyze ORIC results and deductive thematic analysis, employing a codebook guided by the Consolidated Framework for Implementation Research (CFIR), to synthesize themes in barriers and facilitators across sites, and by rurality. Results: Results from the ORIC scale indicated strong perceptions of organizational readiness across all sites. Staff from rural areas reported greater confidence in their ability to manage the politics of change (87% rural, 76% non-rural) and in their organization's ability to support staff adjusting to the change (96% rural, 75% non-rural). Staff at both rural and non-rural sites highlighted factors reflective of the Intervention Characteristics (relative advantage) and Implementation Climate (compatibility and tension for change) domains as facilitators. Although few barriers to implementation were reported, differences arose between rural and non-rural sites in these perceived barriers, with non-rural staff more often raising concerns about resistance to change and compatibility with existing work processes and rural staff more often raising concerns about competing time demands and limited resources. Conclusions: Staff across both rural and non-rural settings identified few, but different, barriers to implementing a novel FN intervention that they perceived as important and responsive to patients' needs. These findings can inform how strategies are tailored to support FN in diverse oncology practices.

Financial navigation: Staff perspectives on patients' financial burden of cancer care.

PURPOSE: To describe perceptions of financial navigation staff concerning patients' cancer-related financial burden. METHODS: This qualitative descriptive study used a semi-structured interview guide to examine perceptions of financial navigation staff concerning patients' cancer-related financial burden. Staff who provided financial navigation support services to cancer patients were interviewed from different types of cancer programs across seven states representing rural, micropolitan, and urban settings. Interviews lasted approximately one hour, were audio recorded, and transcribed. Transcripts were double coded for thematic analysis. RESULTS: Thirty-five staff from 29 cancer centers were interviewed. The first theme involved communication issues related to patient and financial navigation staff expectations, timing and the sensitive nature of financial discussions. The second theme involved the multi-faceted impact of financial burden on patients, including stress, difficulty adhering to treatments, and challenges meeting basic, non-medical needs. CONCLUSIONS AND IMPLICATIONS FOR CANCER SURVIVORS: Cancer-related financial burden has a profound impact on cancer survivors' health and non-health outcomes. Discussions regarding cancer-related costs between cancer survivors and healthcare team members could help to normalize conversations and mitigate the multi-faceted determinants and effects of cancer-related financial burden. As treatment may span months and years and unexpected costs arise, having this discussion regularly and systematically is needed.

Lessening the Impact of Financial Toxicity (LIFT): a protocol for a multi-site, single-arm trial examining the effect of financial navigation on financial toxicity in adult patients with cancer in rural and non-rural settings.

BACKGROUND: Almost half of the patients with cancer report cancer-related financial hardship, termed "financial toxicity" (FT), which affects health-related quality of life, care retention, and, in extreme cases, mortality. This increasingly prevalent hardship warrants urgent intervention. Financial navigation (FN) targets FT by systematically identifying patients at high risk, assessing eligibility for existing resources, clarifying treatment cost expectations, and working with patients and caregivers to develop a plan to cope with cancer costs. This trial seeks to (1) identify FN implementation determinants and implementation outcomes, and (2) evaluate the effectiveness of FN in improving patient outcomes. METHODS: The Lessening the Impact of Financial Toxicity (LIFT) study is a multi-site Phase 2 clinical trial. We use a pre-/post- single-arm intervention to examine the effect of FN on FT in adults with cancer. The LIFT trial is being conducted at nine oncology care settings across North Carolina in the United States. Sites vary in geography (five rural, four non-rural), size (21-974 inpatient beds), and ownership structure (governmental, non-profit). The study will enroll 780 patients total over approximately 2 years. Eligible patients must be 18 years or older, have a confirmed cancer diagnosis (any type) within the past 5 years or be living with advanced disease, and screen positive for cancer-related financial distress. LIFT will be delivered by full- or part-time financial navigators and consists of 3 components: (1) systematic FT screening identification and comprehensive intake assessment; (2) connecting patients experiencing FT to financial support resources via trained oncology financial navigators; and (3) ongoing check-ins and electronic tracking of patients' progress and outcomes by financial navigators. We will measure intervention effectiveness by evaluating change in FT (via the validated Comprehensive Score of Financial Toxicity, or COST instrument) (primary outcome), as well as health-related quality of life (PROMIS Global Health Questionnaire), and patient-reported delayed or forgone care due to cost. We also assess patient- and stakeholder-reported implementation and service outcomes post-intervention, including uptake, fidelity, acceptability, cost, patient-centeredness, and timeliness. DISCUSSION: This study adds to the growing evidence on FN by evaluating its implementation and effectiveness across diverse oncology care settings. TRIAL REGISTRATION: ClinicalTrials.gov NCT04931251. Registered on June 18, 2021.

Financial Assistance Processes and Mechanisms in Rural and Nonrural Oncology Care Settings.

PURPOSE: Patients with cancer are at heightened risk of experiencing financial hardship. Financial navigation (FN) is an evidence-based approach for identifying and addressing patient and caregiver financial needs. In preparation for the implementation of a multisite FN intervention, we describe existing processes (ie, events and actions) and mechanisms (ie, how events work together) connecting patients to financial assistance, comparing rural and nonrural practices. METHODS: We conducted in-depth, semistructured interviews with stakeholders (ie, administrators, providers, and staff) at each of the 10 oncology care sites across a single state (five rural and five nonrural practices). We developed process maps for each site and analyzed stakeholder perspectives using thematic analysis. After reporting findings back to stakeholders, we synthesized themes and process maps across rural and nonrural sites separately. RESULTS: Eighty-three stakeholders were interviewed. We identified six core elements of existing financial assistance processes across all sites: distress screening (including financial concerns), referrals, resource connection points, and pharmaceutical, insurance, and community/foundation resources. Processes differed by rurality; however, facilitators and barriers to identifying and addressing patient financial needs were consistent. Open communication between staff, providers, patients, and caregivers was a primary facilitator. Barriers included insufficient staff resources, challenges in routinely identifying needs, inadequate preparation of patients for anticipated medical costs, and limited tracking of resource availability and eligibility. CONCLUSION: This study identified a clear need for systematic implementation of oncology FN to equitably address patient and caregiver financial hardship. Results have informed our current efforts to implement a multisite FN intervention, which involves comprehensive financial toxicity screening and systematization of intake and referrals.

Interventions to address cancer-related financial toxicity: Recommendations from the field.

PURPOSE: Addressing financial toxicity among cancer patients is a complex process that requires a multifaceted approach, particularly for rural patients who may face additional cost-related barriers to care. In this study, we examined interventions being implemented by financial navigation staff at various cancer centers that help address financial toxicity experienced by oncology patients. METHODS: We conducted semistructured interviews with a convenience sample of financial navigation staff across 29 cancer centers in both rural and urban areas in 7 states. Interviews were audio-recorded and transcribed. Descriptive coding and thematic analysis techniques were used to analyze the data. FINDINGS: Thirty-five participants were interviewed, the majority of whom worked in cancer centers located in rural counties. Participants identified the use of screening tools, patient education, and access to tailored financial assistance resources as best practices. Immediate resource needs included additional financial navigation staff, including lay navigators and community health workers, to promote linkages to local resources. Suggested clinical areas for intervention included proactive and early implementation of financial assessments and discussions between providers and patients, along with training and access to regularly updated resources for those in financial navigator/counselor roles. Participants also discussed the need for policy-level interventions to reform health systems (including employment protections) and health insurance programs. CONCLUSIONS: Implementing proactive methods to screen for and address financial needs of patients is essential to improving cancer-related outcomes. Additional programs and research are needed to help establish systematic and standardized methods to enhance financial navigation services, especially for underserved rural communities.

How cancer programs identify and address the financial burdens of rural cancer patients.

PURPOSE: Financial toxicity is associated with negative patient outcomes, and rural populations are disproportionately affected by the high costs of cancer care compared to urban populations. Our objective was to (1) understand cancer programs' perceptions of rural-urban differences in cancer patients' experiences of financial hardship, (2) evaluate the resources available to cancer patients across the rural-urban continuum, and (3) determine how rural and urban health care teams assess and address financial distress in cancer patients. METHODS: Seven research teams within the Cancer Prevention and Research Control Network conducted semi-structured interviews with cancer program staff who have a role in connecting cancer patients with financial assistance services in both rural and urban counties. Interviews were audio-recorded and transcribed. We identified themes using descriptive content and thematic analysis. RESULTS: We interviewed 35 staffs across 29 cancer care programs in seven states, with roughly half of respondents from programs in rural counties. Participants identified differences in rural and urban patients' experiences of financial hardship related to distance required to travel for treatment, underinsurance, and low socioeconomic status. Insufficient staffing was an identified barrier to addressing rural and urban patients' financial concerns. CONCLUSIONS: Improved financial navigation services could mitigate the effects of financial toxicity experienced by cancer patients, particularly rural patients, throughout treatment and survivorship. Future research is needed to improve how cancer programs assess financial hardship in patients and to expand financial navigation services to better serve rural cancer patients.

Healthy Lifestyle Behaviors: Nursing Considerations for Social Determinants of Health.

BACKGROUND: Nurses develop meaningful and deep connections with patients, making them particularly skilled to consider how social determinants of health (SDOH) affect patients. SDOH include one's neighborhood and built environment, health and health care, social and community context, education, and economic stability. Consideration of SDOH, in addition to individual factors, allows nurses to better support patient engagement in health behaviors. OBJECTIVES: This article aims to explore how nurses consider SDOH when talking about health behaviors with patients and to provide case exemplars of how incorporation of the SDOH can be increased in holistic, patient-centered nursing care. METHODS: A secondary data analysis was conducted to identify how practicing oncology nurses (N = 75) take SDOH into account when talking about physical activity with patients. FINDINGS: Of the 124 considerations that nurses made when talking about physical activity with patients, most did not relate to SDOH.

Deficiency of Antioxidative Paraoxonase 2 (Pon2) Leads to Increased Number of Phenotypic LT-HSCs and Disturbed Erythropoiesis.

BACKGROUND: Long-term hematopoietic stem cells (LT-HSCs) reside in bone marrow niches with tightly controlled reactive oxygen species (ROS) levels. ROS increase results into LT-HSC differentiation and stem cell exhaustion. Paraoxonase 2 (PON2) has been shown to be important for ROS control. OBJECTIVES: We investigate the effects of inactivation of the PON2 gene on hematopoietic cell differentiation and activity. METHODS AND RESULTS: In young mice with inactivated Pon2 gene (Pon2 -/-, <3 months), we observed an increase of LT-HSCs and a reduced frequency of progenitor cells. In competitive transplantations, young Pon2-/- BM outcompeted WT BM at early time points. ROS levels were significantly increased in Pon2-/- whole BM, but not in Pon2-/- LT-HSCs. In more differentiated stages of hematopoiesis, Pon2 deficiency led to a misbalanced erythropoiesis both in physiologic and stress conditions. In older mice (>9 months), Pon2 depletion caused an increase in LT-HSCs as well as increased levels of granulocyte/macrophage progenitors (GMPs) and myeloid skewing, indicating a premature aging phenotype. No significant changes in ROS levels in old Pon2-/- LT- and short-term (ST-) HSCs were observed, but a significant reduction of spontaneous apoptotic cell death was measured. RNA-seq analysis in Pon2 -/- LT-HSCs identified overrepresentation of genes involved in the C-X-C chemokine receptor type 4 (Cxcr4) signaling, suggesting compensatory mechanisms to overcome ROS-mediated accelerated aging in hematopoietic progenitor cells. CONCLUSIONS: In summary, our current data indicate that PON2 is involved in the regulation of HSC functions.

Impaired Platelet Function in Sept8-Deficient Mice In Vitro.

Septins (Septs) are a widely expressed protein family of 13 mammalian members, recognized as a unique component of the cytoskeleton. In human platelets, we previously described that SEPT4 and SEPT8 are localized surrounding α-granules and move to the platelet surface after activation, indicating a possible role in platelet physiology. In this study, we investigated the impact of Sept8 on platelet function in vitro using Sept8-deficient mouse platelets. Deletion of Sept8 in mouse platelets caused a pronounced defect in activation of the fibrinogen receptor integrin αIIbß3, α-granule exocytosis, and aggregation, especially in response to the glycoprotein VI agonist convulxin. In contrast, δ-granule and lysosome exocytosis of Sept8-deficient platelets was comparable to wild-type platelets. Sept8-deficient platelet binding to immobilized fibrinogen under static conditions was diminished and spreading delayed. The procoagulant activity of Sept8-deficient platelets was reduced in response to convulxin as determined by lactadherin binding. Also thrombin generation was decreased relative to controls. Thus, Sept8 is required for efficient integrin αIIbß3 activation, α-granule release, platelet aggregation, and contributes to platelet-dependent thrombin generation. These results revealed Sept8 as a modulator of distinct platelet functions involved in primary and secondary hemostatic processes.

Quality Improvement Coaching for Human Papillomavirus Vaccination Coverage: A Process Evaluation in 3 States, 2018-2019.

PURPOSE AND OBJECTIVES: Quality improvement (QI) coaching improves human papillomavirus (HPV) vaccination coverage, but effects of coaching have been small, and little is known about how and when QI coaching works. To assess implementation outcomes and explore factors that might explain variation in outcomes, we conducted a process evaluation of a QI coaching intervention for HPV vaccination. INTERVENTION APPROACH: QI coaches received tools and training to support 4 core coaching competencies: 1) expertise in using clinic-level adolescent vaccination data to drive change, 2) knowledge of the evidence base to support change in HPV vaccination practice, 3) familiarity with improvement strategies and action planning, and 4) skill in building relationships. EVALUATION METHODS: Our mixed methods evaluation involved collecting quantitative data through effort-tracking logs and gathering qualitative data through in-depth interviews with QI coaches (N = 11) who worked with 89 clinics in 3 US states. Data were collected on implementation outcomes and on contextual factors that might explain variations in those outcomes. Implementation outcomes included adoption by clinics, reach to providers and staff (ie, participation in the coaching visit), and implementation fidelity. RESULTS: States achieved either high adoption or high reach, but not both. For example, state A had high adoption with 94% of clinics accepting a coaching visit, but low reach with a median of 1 participant per clinic. In contrast, state C had lower adoption (29%, P < .01) than state A but higher reach (median of 4 participants per clinic, P < .01). Generally, states had high coaching protocol fidelity with the exception of advising on strategies and action planning. QI coaches described factors that might explain these variations, including strength of relationships with clinic staff and whether they recruited clinics directly or through large clinic networks. IMPLICATIONS FOR PUBLIC HEALTH: Our findings have implications for the design of future QI coaching initiatives, including how coaches recruit clinics to ensure full clinic engagement, refinements to coaching visits, and how QI coaches can effectively engage with clinic networks. Findings could inform future QI coaching interventions to strengthen their impact on public health.

NOX2ko Mice Show Largely Increased Expression of a Mutated NOX2 mRNA Encoding an Inactive NOX2 Protein.

BACKGROUND: The superoxide-generating enzyme nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (NOX2 or gp91phox, the phagocytic isoform) was reported as a major source of oxidative stress in various human diseases. Genetic deletion is widely used to study the impact of NOX2-derived reactive oxygen species (ROS) on disease development and progression in various animal models. Here, we investigate why NOX2 knockout mice show no NOX2 activity but express NOX2 mRNA and protein. METHODS AND RESULTS: Oxidative burst (NOX2-dependent formation of ROS) was measured by L-012-based chemiluminescence and was largely absent in whole blood of NOX2 knockout mice. Protein expression was still detectable in different tissues of the NOX2 knockout mice, at the expected and a slightly lower molecular weight (determined by Western blot). The NOX2 gene was even largely enhanced at its expressional level in NOX2 knockout mice. RNA sequencing revealed a modified NOX2 mRNA in the knockout mice that is obviously translated to a truncated inactive mutant enzyme. CONCLUSION: Although the commercial NOX2 knockout mice display no considerable enzymatic NOX2 activity, expression of the NOX2 gene (when using standard primers) and protein (when using antibodies binding to the carboxy-terminal end) can still be detected, which may lead to confusion among investigators.

Challenges of using nationally representative, population-based surveys to assess rural cancer disparities.

Population-based surveys provide important information about cancer-related health behaviors across the cancer care continuum, from prevention to survivorship, to inform cancer control efforts. These surveys can illuminate cancer disparities among specific populations, including rural communities. However, due to small rural sample sizes, varying sampling methods, and/or other study design or analytical concerns, there are challenges in using population-based surveys for rural cancer control research and practice. Our objective is three-fold. First, we examined the characterization of "rural" in four, population-based surveys commonly referenced in the literature: 1) Health Information National Trends Survey (HINTS); 2) National Health Interview Survey (NHIS); 3) Behavioral Risk Factor Surveillance System (BRFSS); and 4) Medical Expenditures Panel Survey (MEPS). Second, we identified and described the challenges of using these surveys in rural cancer studies. Third, we proposed solutions to address these challenges. We found that these surveys varied in use of rural-urban classifications, sampling methodology, and available cancer-related variables. Further, we found that accessibility of these data to non-federal researchers has changed over time. Survey data have become restricted based on small numbers (i.e., BRFSS) and have made rural-urban measures only available for analysis at Research Data Centers (i.e., NHIS and MEPS). Additionally, studies that used these surveys reported varying proportions of rural participants with noted limitations in sufficient representation of rural minorities and/or cancer survivors. In order to mitigate these challenges, we propose two solutions: 1) make rural-urban measures more accessible to non-federal researchers and 2) implement sampling approaches to oversample rural populations.

Examining Urban and Rural Differences in How Distance to Care Influences the Initiation and Completion of Treatment among Insured Cervical Cancer Patients.

BACKGROUND: Although rural cancer patients encounter substantial barriers to care, they more often report receiving timely care than urban patients. We examined whether geographic distance, a contributor to urban-rural health disparities, differentially influences treatment initiation and completion among insured urban and rural cervical cancer patients. METHODS: We identified women diagnosed with cervical cancer from 2004 to 2013 from a statewide cancer registry linked to multipayer, insurance claims. Primary outcomes were initiation of guideline-concordant care within 6 weeks of diagnosis and, among stage IB2-IVA cancer patients, completion of concurrent chemoradiotherapy (CCRT) in 56 days. We estimated risk ratios using modified Poisson regressions, stratified by urban/rural status, to examine the association between distance and treatment timing (initiation or completion). RESULTS: Among 999 stage IA-IVA patients, 48% initiated guideline-concordant care within 6 weeks of diagnosis, and 37% of 492 stage IB2-IVA cancer patients completed CCRT in 56 days. In urban areas, stage IA-IVA patients who lived ≥15 miles from the nearest treatment facility were less likely to initiate timely treatment compared with those <5 miles [risk ratio (RR): 0.72; 95% confidence intervals (CI), 0.54-0.95]. Among IB2-IVA stage cancer patients, rural women residing ≥15 miles from the nearest radiation facility were more likely to complete CCRT in 56 days (RR: 2.49; 95% CI, 1.12-5.51). CONCLUSIONS: Geographic distance differentially influences the initiation and completion of treatment among urban and rural cervical cancer patients. IMPACT: Distance was an access barrier for insured cervical cancer patients in urban areas whereas rural patients may require more intensive outreach, support, and resources, even among those living closer to treatment.

Does State-Level Nurse Practitioner Scope-of-Practice Policy Affect Access to Care?

There is heated debate surrounding policy reform granting full state-level nurse practitioner (NP) scope of practice (SOP) in all U.S. states. NP SOP policy is argued to impact access to care; however, a synthesis of empirical studies assessing this relationship has yet to be performed. Our study fills this critical gap by systematically reviewing studies that examine this relationship. We apply Aday and Andersen's Access Framework to operationalize access to care. We also use this framework to map components of access to care that may relate to NP SOP through concepts identified in this review. Our findings suggest that full state-level NP SOP policy is associated with increases in various components of access to care, but additional work is needed to evaluate causality and underlying mechanisms behind this policy's effect on access. This work is necessary to align research, practice, and policy efforts surrounding NP SOP with healthcare accessibility.

Evaluating the urban-rural paradox: The complicated relationship between distance and the receipt of guideline-concordant care among cervical cancer patients.

OBJECTIVE: Urban-rural health disparities are often attributed to the longer distances rural patients travel to receive care. However, a recent study suggests that distance to care may affect urban and rural cancer patients differentially. We examined whether this urban-rural paradox exists among patients with cervical cancer. METHODS: We identified individuals diagnosed with cervical cancer from 2004 to 2013 using a statewide cancer registry linked to multi-payer, insurance claims. Our primary outcome was receipt of guideline-concordant care: surgery for stages IA1-IB1; external beam radiation therapy (EBRT), concomitant chemotherapy, and brachytherapy for stages IB2-IVA. We estimated risk ratios (RR) using modified Poisson regressions, stratified by urban/rural location, to examine the association between distance to nearest facility and receipt of treatment. RESULTS: 62% of 999 cervical cancer patients received guideline-concordant care. The association between distance and receipt of care differed by type of treatment. In urban areas, cancer patients who lived ≥15 miles from the nearest surgical facility were less likely to receive primary surgical management compared to those <5 miles from the nearest surgical facility (RR: 0.77, 95% CI: 0.60-0.98). In rural areas, patients living ≥15 miles from the nearest brachytherapy facility were more likely to receive treatment compared to those <5 miles from the nearest brachytherapy facility (RR: 1.71, 95% CI: 1.14-2.58). Distance was not associated with the receipt of chemotherapy or EBRT. CONCLUSIONS: Among cervical cancer patients, there is evidence supporting the urban-rural paradox, i.e., geographic distance to cancer care facilities is not consistently associated with treatment receipt in expected or consistent ways. Healthcare systems must consider the diverse and differential barriers encountered by urban and rural residents to improve access to high quality cancer care.