RESUMO
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.
Assuntos
Adenocarcinoma , Neoplasias Esofágicas , Qualidade de Vida , Humanos , Renda , Junção EsofagogástricaRESUMO
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.
Assuntos
Cuidadores , Efeitos Psicossociais da Doença , Gastos em Saúde , Neoplasias , Adulto , Escolaridade , Apoio Financeiro , Humanos , Pessoa de Meia-Idade , Neoplasias/economia , Neoplasias/terapia , Projetos PilotoRESUMO
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.
Assuntos
Cerebelo/metabolismo , Expansão das Repetições de DNA , Proteínas/genética , Idoso , Idoso de 80 Anos ou mais , Esclerose Lateral Amiotrófica/complicações , Esclerose Lateral Amiotrófica/genética , Esclerose Lateral Amiotrófica/metabolismo , Esclerose Lateral Amiotrófica/patologia , Proteína C9orf72 , Cerebelo/patologia , Transtornos Cognitivos/complicações , Transtornos Cognitivos/genética , Transtornos Cognitivos/metabolismo , Transtornos Cognitivos/patologia , Estudos de Coortes , Feminino , Lobo Frontal/metabolismo , Lobo Frontal/patologia , Demência Frontotemporal/complicações , Demência Frontotemporal/genética , Demência Frontotemporal/metabolismo , Demência Frontotemporal/patologia , Heterozigoto , Hipocampo/metabolismo , Hipocampo/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Córtex Motor/metabolismo , Córtex Motor/patologia , Doença dos Neurônios Motores/complicações , Doença dos Neurônios Motores/genética , Doença dos Neurônios Motores/metabolismo , Doença dos Neurônios Motores/patologia , Biossíntese de Proteínas , RNA Mensageiro/metabolismoRESUMO
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.
Assuntos
Esclerose Lateral Amiotrófica/sangue , Esclerose Lateral Amiotrófica/líquido cefalorraquidiano , Proteínas de Neurofilamentos/sangue , Proteínas de Neurofilamentos/líquido cefalorraquidiano , Idoso , Envelhecimento/metabolismo , Biomarcadores/sangue , Biomarcadores/líquido cefalorraquidiano , Estudos de Coortes , Progressão da Doença , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Debilidade Muscular/etiologia , Prognóstico , SobrevidaRESUMO
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.
Assuntos
Anatomia/educação , Educação Continuada , Manuscritos como Assunto , Publicações Periódicas como Assunto , Fisiologia/educação , HumanosRESUMO
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.
Assuntos
Esclerose Lateral Amiotrófica/sangue , Esclerose Lateral Amiotrófica/patologia , Axônios/metabolismo , Proteínas de Neurofilamentos/sangue , Adulto , Fatores Etários , Idoso , Esclerose Lateral Amiotrófica/genética , Animais , Biomarcadores/sangue , Modelos Animais de Doenças , Progressão da Doença , Ensaio de Imunoadsorção Enzimática/métodos , Feminino , Regulação da Expressão Gênica/genética , Humanos , Masculino , Camundongos , Camundongos Transgênicos , Pessoa de Meia-Idade , Mutação/genética , Neurônios/patologia , Proteínas Nucleares/metabolismo , Fosforilação , Superóxido Dismutase/genética , Proteínas Supressoras da Sinalização de Citocina/metabolismoRESUMO
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.
Assuntos
Falência da Empresa/estatística & dados numéricos , Lesões Encefálicas/economia , Traumatismos da Medula Espinal/economia , Adulto , Lesões Encefálicas/epidemiologia , Estudos Transversais , Emprego/estatística & dados numéricos , Feminino , Financiamento Pessoal/estatística & dados numéricos , Gastos em Saúde/estatística & dados numéricos , Humanos , Renda/estatística & dados numéricos , Masculino , Prevalência , Sistema de Registros , Traumatismos da Medula Espinal/epidemiologia , Washington/epidemiologiaRESUMO
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.
Assuntos
Oncologia/economia , Navegação de Pacientes/economia , Adulto , Idoso , Efeitos Psicossociais da Doença , Feminino , Custos de Cuidados de Saúde , Humanos , Seguro Saúde , Masculino , Oncologia/métodos , Pessoa de Meia-Idade , Projetos Piloto , Estudos Prospectivos , Fatores SocioeconômicosRESUMO
The implementation of managed health care two decades ago produced sweeping changes in the delivery of health care. A large number of patients who have depression are cared for in managed care settings. Despite the fact that managed health care programs have offered the advantage of affordable and effective treatment of depression to many patients, racial and ethnic minorities remain underdiagnosed and undertreated. Diagnosis of depression, prescribing of antidepressant therapy, and referral for psychotherapy occur significantly less often in minority patients compared with whites. In the managed care setting, a number of issues at the physician level may negatively affect the quality of depression care, including attitudes toward psychiatry and mental health services, unfamiliarity with best practice guidelines for depression, and lack of cultural competency. On the other hand, a number of innovative approaches (eg, collaborative care) have demonstrated effectiveness in managed care settings. In some cases, physician education can be integrated with these approaches to assist health care providers in managed care organizations to provide the best possible depression care. This article focuses on issues relevant to depression care of minorities in the managed care sector, cites strategies for improving quality of depression care, and discusses implications for CME.
Assuntos
Depressão/etnologia , Depressão/terapia , Disparidades nos Níveis de Saúde , Programas de Assistência Gerenciada , Educação Médica Continuada , Etnicidade , História do Século XX , História do Século XXI , Humanos , Programas de Assistência Gerenciada/história , Programas de Assistência Gerenciada/normas , Equipe de Assistência ao Paciente , Qualidade da Assistência à Saúde , Grupos Raciais , Estados UnidosRESUMO
Despite improved awareness among the medical community concerning common mental health disorders, the high prevalence of depression in the United States remains unchanged and has been compounded by increasing evidence of gaps in mental health care for ethnic and racial minorities. Thus, there is a strong need for the timely creation of comprehensive educational initiatives aimed at improving the quality of care provided by mental health professionals and primary care physicians. Fundamental to this process is the examination of current treatment standards, as well as identification of practices that require improved physician education. Consistent use of appropriate screening tools, diagnostic accuracy and timeliness, continual assessment of illness severity, adherence to practice guidelines, and individualized patient care need heightened attention to improve outcomes. This article describes the most prevalent types of depression and summarizes current practices in depression care, with an emphasis on treatment standards and opportunities for improved performance.
Assuntos
Depressão/etnologia , Depressão/terapia , Disparidades em Assistência à Saúde , Qualidade da Assistência à Saúde , Depressão/diagnóstico , Depressão/epidemiologia , Educação Médica Continuada , Humanos , Programas de Rastreamento , Guias de Prática Clínica como Assunto , Estados Unidos/epidemiologiaRESUMO
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.
Assuntos
Depressão/diagnóstico , Depressão/terapia , Educação Médica Continuada , Disparidades em Assistência à Saúde , Depressão/etnologia , Etnicidade , Humanos , Programas de Assistência Gerenciada , Qualidade da Assistência à Saúde , Grupos RaciaisRESUMO
Depression is one of the most common reasons that individuals seek treatment in the primary care setting. Research in the past 15 years has shown that dramatic improvement in the management of patients with depression is possible. Advances in pharmacotherapy and delivery of depression care have been reported, but few currently benefit members of ethnic and racial minorities. Educating physicians and other health professionals has been suggested as one approach to address the issues related to disparities in depression care. There is little evidence, however, that education alone is effective. The authors of this article believe that incorporating physician learning activities that are planned using approaches that have been shown to be effective in interventions currently demonstrating some success in improving depression care provided to ethnic and racial minorities will enhance the impact and sustainability of these interventions. This article--the conclusion of this supplement--will describe an intervention concept that integrates a quality improvement model (the Institute for Health Improvement's Breakthrough Series Collaborative model) with an evidence-based approach to planning CME and supports the integration by using action inquiry technologies and community-based participatory research methods. Relevant approaches from implementation research are discussed, and suggestions for testing the intervention concept are provided.
Assuntos
Depressão/etnologia , Depressão/terapia , Educação Médica Continuada , Etnicidade , Medicina Baseada em Evidências , Disparidades em Assistência à Saúde , Humanos , Equipe de Assistência ao Paciente , Grupos Raciais , Estados UnidosRESUMO
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.
Assuntos
Neoplasias da Mama/economia , Neoplasias Colorretais/economia , Efeitos Psicossociais da Doença , Educação de Pacientes como Assunto/métodos , Estudos de Coortes , Emprego , Feminino , Humanos , Entrevistas como Assunto , Masculino , Pessoa de Meia-Idade , Inquéritos e Questionários , Estados UnidosRESUMO
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.
Assuntos
Falência da Empresa/estatística & dados numéricos , Neoplasias/mortalidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias/economia , Neoplasias/psicologia , Neoplasias/terapia , Modelos de Riscos Proporcionais , Fatores de Risco , Programa de SEER , Estresse Psicológico/economia , Estresse Psicológico/etiologia , Estresse Psicológico/psicologia , Washington/epidemiologiaRESUMO
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.
Assuntos
Esclerose Lateral Amiotrófica/genética , Proteínas de Ligação a DNA/genética , Modelos Animais de Doenças , Demência Frontotemporal/genética , Camundongos , Proteínas/genética , Esclerose Lateral Amiotrófica/patologia , Animais , Transtorno da Personalidade Antissocial/genética , Transtorno da Personalidade Antissocial/patologia , Proteína C9orf72 , Córtex Cerebral/metabolismo , Córtex Cerebral/patologia , Dependovirus , Dipeptídeos/metabolismo , Demência Frontotemporal/patologia , Técnicas de Transferência de Genes , Células HEK293 , Humanos , Células de Purkinje/metabolismo , Células de Purkinje/patologia , RNA Nuclear/metabolismoRESUMO
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.
Assuntos
Esclerose Lateral Amiotrófica/genética , Cerebelo/metabolismo , Lobo Frontal/metabolismo , Regulação da Expressão Gênica/genética , Proteínas/genética , RNA/metabolismo , Transcriptoma/genética , Adulto , Idoso , Processamento Alternativo , Proteína C9orf72 , Estudos de Associação Genética , Ribonucleoproteínas Nucleares Heterogêneas Grupo F-H/metabolismo , Humanos , Pessoa de Meia-Idade , Poliadenilação/genética , Análise de Sequência de RNARESUMO
INTRODUCTION: The integrity of medical education and communication companies (MECCs) and their role in continuing medical education (CME) are frequently challenged, perhaps because of a lack of published information characterizing these providers. Published in 1998, a survey of MECCs began the identification and description of these organizations so that meaningful conclusions could be drawn about their role in CME. The present study enhances the profile created by that original survey. METHODS: A 21-item questionnaire was mailed to 182 companies identified from 3 commercially available lists. RESULTS: Forty-six (25.2%) companies responded. Surveys revealed that 25 (54%) of the respondent companies have 1 to 25 employees, 66.6% have separate CME divisions, 64.4% are accredited to provide CME, 77.7% have at least 1 licensed health care professional on staff, and 33.2% of their leaders hold a doctoral degree and 28.8% hold professional licensure, whereas 88.6% have advisory boards, 93.1% of which review each CME activity. DISCUSSION: MECCs comprise a diverse group differing in size and accreditation status. They contribute to the CME community by providing a variety of services, with highly trained staff. Future studies of CME providers should continue to expand the base of knowledge regarding these organizations, resulting in better understanding among all types of providers, opportunities for collaboration, and, ultimately, education that improves patient care.
Assuntos
Educação Médica Continuada/organização & administração , Indústrias/organização & administração , Acreditação , Conflito de Interesses , Comportamento Cooperativo , Coleta de Dados , Indústria Farmacêutica/organização & administração , Indústria Farmacêutica/estatística & dados numéricos , Indústrias/estatística & dados numéricos , Relações Interinstitucionais , Internet , Inquéritos e Questionários , Apoio ao Desenvolvimento de Recursos Humanos , Estados UnidosRESUMO
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.
Assuntos
Esclerose Lateral Amiotrófica/genética , Esclerose Lateral Amiotrófica/metabolismo , Biomarcadores/análise , Expansão das Repetições de DNA/genética , Quadruplex G , Proteínas/genética , Adulto , Idoso , Esclerose Lateral Amiotrófica/líquido cefalorraquidiano , Esclerose Lateral Amiotrófica/patologia , Animais , Proteína C9orf72 , Diferenciação Celular/efeitos dos fármacos , Diferenciação Celular/genética , Células Cultivadas , Chlorocebus aethiops , Feminino , Fibroblastos , Humanos , Masculino , Pessoa de Meia-Idade , Proteínas do Tecido Nervoso/metabolismo , Neurônios/metabolismo , Ligação Proteica , Proteínas/química , RNA Interferente Pequeno/genética , RNA Interferente Pequeno/metabolismoRESUMO
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.