A proactive financial navigation intervention in patients with newly diagnosed gastric and gastroesophageal junction adenocarcinoma.

PURPOSE: Many cancer patients and caregivers experience financial hardship, leading to poor outcomes. Gastric and gastroesophageal junction (GEJ) cancer patients are particularly at risk for financial hardship given the intensity of treatment. This pilot randomized study among gastric/GEJ cancer patients and caregivers tested a proactive financial navigation (FN) intervention to obtain a signal of efficacy to inform a larger, more rigorous randomized study. METHODS: We tested a 3-month proactive FN intervention among gastric/GEJ cancer patients and caregivers compared to usual care. Caregiver participation was optional. The primary endpoint was incidence of financial hardship, defined as follows: accrual of debt, income decline of ≥ 20%, or taking loans to pay for treatment. Data from participant surveys and documentation by partner organizations delivering the FN intervention was analyzed and outcomes were compared between study arms. RESULTS: Nineteen patients and 12 caregivers consented. Primary FN resources provided included insurance navigation, budget planning, and help with out-of-pocket medical expenses. Usual care patients were more likely to experience financial hardship (50% vs 40%) and declines in quality of life (37.5% vs 0%) compared to intervention patients. Caregivers in both arms reported increased financial stress and poorer quality of life over the study period. CONCLUSIONS: Proactive financial navigation has potentially positive impacts on financial hardship and quality of life for cancer patients and more large-scale randomized interventions should be conducted to rigorously explore the impact of similar interventions. Interventions that have the potential to lessen caregiver financial stress and burden need further exploration. TRIAL REGISTRATION: TRN: NCT03986502, June 14, 2019.

A Pilot Study of a Comprehensive Financial Navigation Program in Patients With Cancer and Caregivers.

BACKGROUND: Few studies have engaged patients and caregivers in interventions to alleviate financial hardship. We collaborated with Consumer Education and Training Services (CENTS), Patient Advocate Foundation (PAF), and Family Reach (FR) to assess the feasibility of enrolling patient-caregiver dyads in a program that provides financial counseling, insurance navigation, and assistance with medical and cost of living expenses. METHODS: Patients with solid tumors aged ≥18 years and their primary caregiver received a financial education video, monthly contact with a CENTS counselor and PAF case manager for 6 months, and referral to FR for help with unpaid cost of living bills (eg, transportation or housing). Patient financial hardship and caregiver burden were measured using the Comprehensive Score for Financial Toxicity-Patient-Reported Outcomes (COST-PRO) and Caregiver Strain Index (CSI) measures, respectively, at baseline and follow-up. RESULTS: Thirty patients (median age, 59.5 years; 40% commercially insured) and 18 caregivers (67% spouses) consented (78% dyad participation rate). Many participants faced cancer-related financial hardships prior to enrollment, such as work change or loss (45% of patients; 39% of caregivers) and debt (64% of patients); 39% of caregivers reported high levels of financial burden at enrollment. Subjects received $11,000 in assistance (mean, $772 per household); 66% of subjects with income ≤$50,000 received cost-of-living assistance. COST-PRO and CSI scores did not change significantly. CONCLUSIONS: Patient-caregiver dyads were willing to participate in a financial navigation program that addresses various financial issues, particularly cost of living expenses in lower income participants. Future work should address financial concerns at diagnosis and determine whether doing so improves patient and caregiver outcomes.

Pilot Feasibility Study of an Oncology Financial Navigation Program.

BACKGROUND: Few studies have reported on interventions to alleviate financial toxicity in patients with cancer. We developed a financial navigation program in collaboration with our partners, Consumer Education and Training Services (CENTS) and Patient Advocate Foundation (PAF), to improve patient knowledge about treatment costs, provide financial counseling, and to help manage out-of-pocket expenses. We conducted a pilot study to assess the feasibility and impact of this program. METHODS: Patients with cancer received a financial education course followed by monthly contact with a CENTS financial counselor and a PAF case manager for 6 months. We measured program adherence, self-reported financial burden and anxiety, program satisfaction, and type of assistance provided. RESULTS: Thirty-four patients (median age, 60.5 years) were consented (85% white and 50% commercially insured). Debt, income declines, and loans were reported by 55%, 55%, and 30% of patients, respectively. CENTS counselors assisted most often with budgeting, retirement planning, and medical bill questions. PAF case managers assisted with applications for appropriate insurance coverage, cost of living issues (eg, housing, transportation), and disability applications. High financial burden and anxiety about costs (4 or 5 on a Likert scale) were reported at baseline by 37% and 47% of patients, respectively. Anxiety about costs decreased over time in 33% of patients, whereas self-reported financial burden did not substantially change. CONCLUSION: Implementing an oncology financial navigation program is feasible, provides concrete assistance in navigating the cost of care, and mitigates anxiety about costs in a subset of patients. Future work will focus on measuring the program's impact on financial and clinical outcomes.

Development of a financial literacy course for patients with newly diagnosed cancer.

OBJECTIVES: Although patients with cancer often face serious financial hardships, few studies have reported on strategies to mitigate this burden. Improving literacy about the financial aspects of cancer care may decrease the negative financial impact of cancer diagnosis and treatment. We obtained input from patient stakeholders on the perceived value and optimal design of a financial literacy program in the advanced cancer setting. STUDY DESIGN: Prospective cohort survey. METHODS: A series of semi-structured interviews were conducted, during which patients with either colorectal or breast cancer were asked to describe the impact of cancer on their finances and employment, to state their preferences about discussing costs with their providers, and to give input on development of a financial literacy course. RESULTS: Twenty-one patients (76% Caucasian) completed interviews, the majority of whom had Medicare or commercial insurance (71%). Lost income from early retirement or disability was the most financially burdensome experience for 67% of patients. The majority of patients (76%) reported that a financial literacy course would be helpful in navigating the cost of cancer care. Most preferred the course be administered at diagnosis in a live group format. CONCLUSIONS: Feedback from patients with cancer supported the development of a group financial literacy course that addresses barriers to discussing cost concerns, employment changes during cancer, and available resources for financial assistance.

Financial Insolvency as a Risk Factor for Early Mortality Among Patients With Cancer.

PURPOSE: Patients with cancer are more likely to file for bankruptcy than the general population, but the impact of severe financial distress on health outcomes among patients with cancer is not known. METHODS: We linked Western Washington SEER Cancer Registry records with federal bankruptcy records for the region. By using propensity score matching to account for differences in several demographic and clinical factors between patients who did and did not file for bankruptcy, we then fit Cox proportional hazards models to examine the relationship between bankruptcy filing and survival. RESULTS: Between 1995 and 2009, 231,596 persons were diagnosed with cancer. Patients who filed for bankruptcy (n = 4,728) were more likely to be younger, female, and nonwhite, to have local- or regional- (v distant-) stage disease at diagnosis, and have received treatment. After propensity score matching, 3,841 patients remained in each group (bankruptcy v no bankruptcy). In the matched sample, mean age was 53.0 years, 54% were men, mean income was $49,000, and majorities were white (86%), married (60%), and urban (91%) and had local- or regional-stage disease at diagnosis (84%). Both groups received similar initial treatments. The adjusted hazard ratio for mortality among patients with cancer who filed for bankruptcy versus those who did not was 1.79 (95% CI, 1.64 to 1.96). Hazard ratios varied by cancer type: colorectal, prostate, and thyroid cancers had the highest hazard ratios. Excluding patients with distant-stage disease from the models did not have an effect on results. CONCLUSION: Severe financial distress requiring bankruptcy protection after cancer diagnosis appears to be a risk factor for mortality. Further research is needed to understand the process by which extreme financial distress influences survival after cancer diagnosis and to find strategies that could mitigate this risk.

Cerebellar c9RAN proteins associate with clinical and neuropathological characteristics of C9ORF72 repeat expansion carriers.

Clinical and neuropathological characteristics associated with G4C2 repeat expansions in chromosome 9 open reading frame 72 (C9ORF72), the most common genetic cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia, are highly variable. To gain insight on the molecular basis for the heterogeneity among C9ORF72 mutation carriers, we evaluated associations between features of disease and levels of two abundantly expressed "c9RAN proteins" produced by repeat-associated non-ATG (RAN) translation of the expanded repeat. For these studies, we took a departure from traditional immunohistochemical approaches and instead employed immunoassays to quantitatively measure poly(GP) and poly(GA) levels in cerebellum, frontal cortex, motor cortex, and/or hippocampus from 55 C9ORF72 mutation carriers [12 patients with ALS, 24 with frontotemporal lobar degeneration (FTLD) and 19 with FTLD with motor neuron disease (FTLD-MND)]. We additionally investigated associations between levels of poly(GP) or poly(GA) and cognitive impairment in 15 C9ORF72 ALS patients for whom neuropsychological data were available. Among the neuroanatomical regions investigated, poly(GP) levels were highest in the cerebellum. In this same region, associations between poly(GP) and both neuropathological and clinical features were detected. Specifically, cerebellar poly(GP) levels were significantly lower in patients with ALS compared to patients with FTLD or FTLD-MND. Furthermore, cerebellar poly(GP) associated with cognitive score in our cohort of 15 patients. In the cerebellum, poly(GA) levels similarly trended lower in the ALS subgroup compared to FTLD or FTLD-MND subgroups, but no association between cerebellar poly(GA) and cognitive score was detected. Both cerebellar poly(GP) and poly(GA) associated with C9ORF72 variant 3 mRNA expression, but not variant 1 expression, repeat size, disease onset, or survival after onset. Overall, these data indicate that cerebellar abnormalities, as evidenced by poly(GP) accumulation, associate with neuropathological and clinical phenotypes, in particular cognitive impairment, of C9ORF72 mutation carriers.

Distinct brain transcriptome profiles in C9orf72-associated and sporadic ALS.

Increasing evidence suggests that defective RNA processing contributes to the development of amyotrophic lateral sclerosis (ALS). This may be especially true for ALS caused by a repeat expansion in C9orf72 (c9ALS), in which the accumulation of RNA foci and dipeptide-repeat proteins are expected to modify RNA metabolism. We report extensive alternative splicing (AS) and alternative polyadenylation (APA) defects in the cerebellum of c9ALS subjects (8,224 AS and 1,437 APA), including changes in ALS-associated genes (for example, ATXN2 and FUS), and in subjects with sporadic ALS (sALS; 2,229 AS and 716 APA). Furthermore, heterogeneous nuclear ribonucleoprotein H (hnRNPH) and other RNA-binding proteins are predicted to be potential regulators of cassette exon AS events in both c9ALS and sALS. Co-expression and gene-association network analyses of gene expression and AS data revealed divergent pathways associated with c9ALS and sALS.

Neurodegeneration. C9ORF72 repeat expansions in mice cause TDP-43 pathology, neuronal loss, and behavioral deficits.

The major genetic cause of frontotemporal dementia and amyotrophic lateral sclerosis is a G4C2 repeat expansion in C9ORF72. Efforts to combat neurodegeneration associated with "c9FTD/ALS" are hindered by a lack of animal models recapitulating disease features. We developed a mouse model to mimic both neuropathological and clinical c9FTD/ALS phenotypes. We expressed (G4C2)66 throughout the murine central nervous system by means of somatic brain transgenesis mediated by adeno-associated virus. Brains of 6-month-old mice contained nuclear RNA foci, inclusions of poly(Gly-Pro), poly(Gly-Ala), and poly(Gly-Arg) dipeptide repeat proteins, as well as TDP-43 pathology. These mouse brains also exhibited cortical neuron and cerebellar Purkinje cell loss, astrogliosis, and decreased weight. (G4C2)66 mice also developed behavioral abnormalities similar to clinical symptoms of c9FTD/ALS patients, including hyperactivity, anxiety, antisocial behavior, and motor deficits.

Discovery of a biomarker and lead small molecules to target r(GGGGCC)-associated defects in c9FTD/ALS.

A repeat expansion in C9ORF72 causes frontotemporal dementia and amyotrophic lateral sclerosis (c9FTD/ALS). RNA of the expanded repeat (r(GGGGCC)exp) forms nuclear foci or undergoes repeat-associated non-ATG (RAN) translation, producing "c9RAN proteins." Since neutralizing r(GGGGCC)exp could inhibit these potentially toxic events, we sought to identify small-molecule binders of r(GGGGCC)exp. Chemical and enzymatic probing of r(GGGGCC)8 indicate that it adopts a hairpin structure in equilibrium with a quadruplex structure. Using this model, bioactive small molecules targeting r(GGGGCC)exp were designed and found to significantly inhibit RAN translation and foci formation in cultured cells expressing r(GGGGCC)66 and neurons transdifferentiated from fibroblasts of repeat expansion carriers. Finally, we show that poly(GP) c9RAN proteins are specifically detected in c9ALS patient cerebrospinal fluid. Our findings highlight r(GGGGCC)exp-binding small molecules as a possible c9FTD/ALS therapeutic and suggest that c9RAN proteins could potentially serve as a pharmacodynamic biomarker to assess efficacy of therapies that target r(GGGGCC)exp.

Washington State cancer patients found to be at greater risk for bankruptcy than people without a cancer diagnosis.

Much has been written about the relationship between high medical expenses and the likelihood of filing for bankruptcy, but the relationship between receiving a cancer diagnosis and filing for bankruptcy is less well understood. We estimated the incidence and relative risk of bankruptcy for people age twenty-one or older diagnosed with cancer compared to people the same age without cancer by conducting a retrospective cohort analysis that used a variety of medical, personal, legal, and bankruptcy sources covering the Western District of Washington State in US Bankruptcy Court for the period 1995-2009. We found that cancer patients were 2.65 times more likely to go bankrupt than people without cancer. Younger cancer patients had 2-5 times higher rates of bankruptcy than cancer patients age sixty-five or older, which indicates that Medicare and Social Security may mitigate bankruptcy risk for the older group. The findings suggest that employers and governments may have a policy role to play in creating programs and incentives that could help people cover expenses in the first year following a cancer diagnosis.

Phosphorylated neurofilament heavy subunit (pNF-H) in peripheral blood and CSF as a potential prognostic biomarker in amyotrophic lateral sclerosis.

BACKGROUND: The phosphorylated neurofilament heavy subunit (pNF-H), a major structural component of motor axons, is a promising putative biomarker in amyotrophic lateral sclerosis (ALS) but has been studied mainly in CSF. We examined pNF-H concentrations in plasma, serum and CSF as a potential biomarker for disease progression and survival in ALS. METHODOLOGY: We measured pNF-H concentration by monoclonal sandwich ELISA in plasma (n=43), serum and CSF (n=20) in ALS patients collected at the Mayo Clinic Florida and Emory University. We included plasma from an ALS cohort (n=20) from an earlier pilot study in order to evaluate baseline pNF-H levels in relation to disease progression using the Amyotrophic Lateral Sclerosis Functional Rating Scale (ALSFRS-R), survival and anatomical region of ALS onset. RESULTS: Higher pNF-H levels in plasma, serum and CSF showed evidence of association with faster decline in ALSFRS-R. There was evidence for a relationship of higher serum and plasma pNF-H levels with shorter survival, although evidence was weaker for CSF. pNF-H concentration in plasma (n=62) may be higher in patients with bulbar onset than in patients with spinal onset. CONCLUSIONS: In ALS, increased pNF-H concentration in plasma, serum and CSF appears to be associated with faster disease progression. Factors affecting pNF-H levels or their detection in serum and plasma in relation to disease course may differ from those in CSF. Data raising the possibility that site of ALS onset (bulbar vs spinal) may influence pNF-H levels in peripheral blood seems noteworthy but requires confirmation. These data support further study of pNF-H in CSF, serum and plasma as a potential ALS biomarker.

The association between bankruptcy and hospital-presenting attempted suicide: a record linkage study.

The associations between admissions to an emergency department following attempted suicide and personal bankruptcy in the preceding and subsequent 2 years were evaluated. Records from a level 1 trauma center (June 1993-December 2002) in Seattle, WA, were linked with case files from the local U.S. District Bankruptcy Court (June 1991 onward). Univariable and multivariable logistic regression models were used to examine the risk of bankruptcy in (i) the 2 years after and (ii) the 2 years before a suicide attempt using a violent method, compared to patients admitted for any other reason. After adjusting for several confounders, patients who had attempted suicide were more likely than other patients to experience bankruptcy in the following 2 years (OR = 2.10, 95% CIs: 1.29, 3.42). A somewhat weaker association was seen with bankruptcy in the preceding 2 years (OR = 1.68, 95% CIs 1.06; 2.67). Attempted suicide is therefore associated with bankruptcy in the preceding and following 2 years. Changes to legislation, improved mental health counselling for those in financial difficulty, and provision of financial advice to those admitted to hospital following a suicide attempt may reduce future cases of serious self-harm and completed suicide.

The anatomy and physiology of a continuing medical education article: a resource guide for enhancing continuing education.

This article was designed to help healthcare professionals assess their roles and responsibilities as authors of articles certified for CME credit and to develop appropriate objectives to reflect the desired outcomes of education through CME articles.

Immunoreactivity of the phosphorylated axonal neurofilament H subunit (pNF-H) in blood of ALS model rodents and ALS patients: evaluation of blood pNF-H as a potential ALS biomarker.

Levels of neurofilament subunits, potential biomarkers of motor axon breakdown, are increased in amyotrophic lateral sclerosis (ALS) patient's CSF but data on blood are not available. We measured blood levels of the phosphorylated axonal form of neurofilament H (pNF-H) by ELISA in transgenic rodent models of superoxide dismutase 1 (SOD1) ALS, and in 20 ALS patients and 20 similar aged controls monthly for 4 months. All symptomatic rodent ALS models showed robust levels of blood pNF-H, while control rodents or mice transgenic for unmutated SOD1 showed no detectable blood pNF-H. Average pNF-H levels in the G93A SOD1 mouse progressively increased from day 74 through death (day approximately 130). Median blood pNF-H level in ALS patients was 2.8-fold higher than controls (p < 0.001). Median ALSFRS-R declined a median of 0.8 pt/month (p < 0.001); higher baseline pNF-H level appeared to be associated with faster ALSFRS-R decline over 4 months (p = 0.087). The median rate of decline in ALSFRS-R was 1.9 pt/month in patients with baseline pNF-H levels above the median pNF-H value of 0.53 ng/mL; ALSFRS-R declined at a median of 0.6 pt/month in patients below this level. The pNF-H levels were relatively stable month to month in individual patients, raising questions regarding the molecular pathogenesis of ALS. Baseline control human pNF-H levels were higher in men than women and increased minimally over time. These data suggest that blood pNF-H can be used to monitor axonal degeneration in ALS model rodents and support further study of this protein as a potential biomarker of disease prognosis in ALS patients.

Personal bankruptcy after traumatic brain or spinal cord injury: the role of medical debt.

OBJECTIVE: To estimate the prevalence of medical debt among traumatic brain injury (TBI) and spinal cord injury (SCI) patients who discharged their debts through bankruptcy. DESIGN: A cross-sectional comparison of bankruptcy filings of injured versus randomly selected bankruptcy petitioners. SETTING: Patients hospitalized with SCI or TBI (1996-2002) and personal bankruptcy petitioners (2001-2004) in western Washington State. PARTICIPANTS: Subjects (N=186) who filed for bankruptcy, comprised of 93 patients with previous SCI or TBI and 93 randomly selected bankruptcy petitioners. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Medical and nonmedical debt, assets, income, expenses, and employment recorded in the bankruptcy petition. RESULTS: Five percent of randomly selected petitioners and 26% of petitioners with TBI or SCI had substantial medical debt (debt that accounted for more than 20% of all unsecured debts). SCI and TBI petitioners had fewer assets and were more likely to be receiving government income assistance at the time of bankruptcy than controls. SCI and TBI patients with a higher blood alcohol content at injury were more likely to have substantial medical debts (odds ratio=2.70; 95% confidence interval, 1.04-7.00). CONCLUSIONS: Medical debt plays an important role in some bankruptcies after TBI or SCI. We discuss policy options for reducing financial distress after serious injury.

Medical education and communication companies involved in CME: an updated profile.

INTRODUCTION: Medical Education and Communication Companies (MECCs) represent approximately 21% of the providers accredited by the Accreditation Council for Continuing Medical Education (ACCME), yet relatively little is known about these organizations in the greater continuing medical education (CME) community. Two prior studies described them, but powerful changes in the regulatory environment have impacted the structure and organization of these companies. METHODS: The investigators administered a 32-item questionnaire to a select sample of 157 MECCs involved in CME, achieving a response rate of 50.3%. RESULTS: Of the responding organizations, 87% were accredited by the ACCME, with 27% also holding accreditation from the Accreditation Council for Pharmacy Education and the American Nurses Credentialing Center Commission on Accreditation. Eighty-six percent reported no immediate involvement of the company in promotional activities. Fifty-three percent of the survey responders reported being part of a larger organization that included companies involved in promotion, and 88% of these organizations reported implementation of firewalls designed to protect the independence of certified education. DISCUSSION: The survey reveals a sector that is largely privately held and moving from an organizational model that included both certified and promotional activities to one that includes only certified education. These changes, along with the implementation of firewalls to protect certified education from the promotional interests of other companies within their own corporate structure, may help to alleviate concerns about the independence of CME produced by MECCs. However, because MECCs continue to receive the majority of their support from commercial interests, the influence of funding is likely to be an area of lingering concern.

Addressing disparities in diagnosing and treating depression: a promising role for continuing medical education.

Depression is a very common reason that individuals seek treatment in the primary care setting. However, advances in depression management are often not integrated into care for ethnic and racial minorities. This supplement summarizes evidence in six key areas--current practices in diagnosis and treatment, disparities, treatment in managed care settings, quality improvement, physician learning, and community-based participatory research--used to develop an intervention concept described in the concluding article. Evidence of gaps in the care for minorities, while discouraging, presents unique opportunities for medical educators to develop interventions with the potential to change physician behavior and thereby reduce disparities and enhance patient outcomes.