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1.
Ann Surg Oncol ; 31(7): 4349-4360, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38538822

RESUMO

BACKGROUND: Oncology outreach is a common strategy for increasing rural access to cancer care, where traveling oncologists commute across healthcare settings to extend specialized care. Examining the extent to which physician outreach is associated with timely treatment for rural patients is critical for informing outreach strategies. METHODS: We identified a 100% fee-for-service sample of incident breast cancer patients from 2015 to 2020 Medicare claims and apportioned them into surgery and adjuvant therapy cohorts based on treatment history. We defined an outreach visit as the provision of care by a traveling oncologist at a clinic outside of their primary hospital service area. We used hierarchical logistic regression to examine the associations between patient receipt of preoperative care at an outreach visit (preoperative outreach) and > 60-day surgical delay, and patient receipt of postoperative care at an outreach visit (postoperative outreach) and > 60-day adjuvant delay. RESULTS: We identified 30,337 rural-residing patients who received breast cancer surgery, of whom 4071 (13.4%) experienced surgical delay. Among surgical patients, 14,501 received adjuvant therapy, of whom 2943 (20.3%) experienced adjuvant delay. In adjusted analysis, we found that patient receipt of preoperative outreach was associated with reduced odds of surgical delay (odds ratio [OR] 0.75, 95% confidence interval [CI] 0.61-0.91); however, we found no association between patient receipt of postoperative outreach and adjuvant delay (OR 1.04, 95% CI 0.85-1.25). CONCLUSIONS: Our findings indicate that preoperative outreach is protective against surgical delay. The traveling oncologists who enable such outreach may play an integral role in catalyzing the coordination and timeliness of patient-centered care.


Assuntos
Neoplasias da Mama , Acessibilidade aos Serviços de Saúde , Medicare , População Rural , Humanos , Feminino , Neoplasias da Mama/cirurgia , Neoplasias da Mama/terapia , Idoso , População Rural/estatística & dados numéricos , Estados Unidos , Medicare/estatística & dados numéricos , Acessibilidade aos Serviços de Saúde/estatística & dados numéricos , Tempo para o Tratamento/estatística & dados numéricos , Oncologia/estatística & dados numéricos , Seguimentos , Idoso de 80 Anos ou mais , Prognóstico , Planos de Pagamento por Serviço Prestado , Mastectomia
2.
J Cancer Educ ; 2024 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-39103704

RESUMO

Visiting electives provide an opportunity for medical students to engage with radiation oncology (RO) programs, likely influencing residency match outcomes. However, some student's out-of-pocket costs may be prohibitive, and in attempts to offset the financial burden of visiting electives, particularly for students underrepresented in medicine (URiM), some institutions offer scholarships. Here, we characterized the current domestic landscape of funded RO electives. Visiting electives were identified through the FREIDA and VSLO databases in April 2024. Funded elective availability and departmental characteristics were identified via internet search by two independent reviewers. Fisher's exact test was used to determine whether there was a difference in the distribution of scholarships across the US due to the small sample size. Ninety-two visiting electives were identified, with 40 programs offering URiM elective scholarships (43.5%). Twelve (30%) were funded specifically by RO departments, and 28 (70%) were part of broader institutional URiM scholarship initiatives. The median stipend provided was $2000 (IQR $500), range $1000-$5000. Analysis of scholarships by US census division and metro area revealed unequal distribution. Electives in New England, Mountain, and East North Central divisions had higher funding proportion compared to electives in the East South Central, West South Central, and Middle Atlantic divisions. Only 1/9 electives in New York City were funded compared with 4/6 in Los Angeles. Departments with funded electives had more faculty physicians and medical residents. In our review of the 2024 landscape, over 40% of RO electives offer financial support. However, we identified geographical disparities in the distribution of scholarships, highlighting the need for interventions to address unequal access to a wide array of training programs. Our study represents a valuable resource for students interested in RO and highlights the continued need to positively contribute to increasing diversity in the field. Future work exploring the impact of funded electives is needed.

3.
BMC Palliat Care ; 22(1): 59, 2023 May 16.
Artigo em Inglês | MEDLINE | ID: mdl-37189073

RESUMO

INTRODUCTION: Early access to specialty palliative care is associated with better quality of life, less intensive end-of-life treatment and improved outcomes for patients with advanced cancer. However, significant variation exists in implementation and integration of palliative care. This study compares the organizational, sociocultural, and clinical factors that support or hinder palliative care integration across three U.S. cancer centers using an in-depth mixed methods case study design and proposes a middle range theory to further characterize specialty palliative care integration. METHODS: Mixed methods data collection included document review, semi-structured interviews, direct clinical observation, and context data related to site characteristics and patient demographics. A mixed inductive and deductive approach and triangulation was used to analyze and compare sites' palliative care delivery models, organizational structures, social norms, and clinician beliefs and practices. RESULTS: Sites included an urban center in the Midwest and two in the Southeast. Data included 62 clinician and 27 leader interviews, observations of 410 inpatient and outpatient encounters and seven non-encounter-based meetings, and multiple documents. Two sites had high levels of "favorable" organizational influences for specialty palliative care integration, including screening, policies, and other structures facilitating integration of specialty palliative care into advanced cancer care. The third site lacked formal organizational policies and structures for specialty palliative care, had a small specialty palliative care team, espoused an organizational identity linked to treatment innovation, and demonstrated strong social norms for oncologist primacy in decision making. This combination led to low levels of specialty palliative care integration and greater reliance on individual clinicians to initiate palliative care. CONCLUSION: Integration of specialty palliative care services in advanced cancer care was associated with a complex interaction of organization-level factors, social norms, and individual clinician orientation. The resulting middle range theory suggests that formal structures and policies for specialty palliative care combined with supportive social norms are associated with greater palliative care integration in advanced cancer care, and less influence of individual clinician preferences or tendencies to continue treatment. These results suggest multi-faceted efforts at different levels, including social norms, may be needed to improve specialty palliative care integration for advanced cancer patients.


Assuntos
Enfermagem de Cuidados Paliativos na Terminalidade da Vida , Neoplasias , Humanos , Cuidados Paliativos/métodos , Qualidade de Vida , Neoplasias/terapia , Atenção à Saúde
4.
Health Commun ; 38(12): 2730-2741, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-35981599

RESUMO

We describe racially discordant oncology encounters involving EOL decision-making. Fifty-eight provider interviews were content analyzed using the tenets of problematic integration theory. We found EOL discussions between non-Black providers and their Black patients were often complex and anxiety-inducing. That anxiety consisted of (1) ontological uncertainty in which providers characterized the nature of Black patients as distrustful, especially in the context of clinical trials; (2) ontological and epistemological uncertainty in which provider intercultural incompetency and perceived lack of patient health literacy were normalized and intertwined with provider assumptions about patients' religion and support systems; (3) epistemological uncertainty as ambivalence in which providers' feelings conflicted when deciding whether to speak with family members they perceived as lacking health literacy; (4) divergence in which the provider advised palliative care while the family desired surgery or cancer-directed medical treatment; and (5) impossibility when an ontological uncertainty stance of Black distrust was seen as natural by providers and therefore impossible to change. Some communication strategies used were indirect stereotyping, negotiating, asking a series of value questions, blame-guilt framing, and avoidance. We concluded that provider perceptions of Black distrust, religion, and social support influenced their ability to communicate effectively with patients.


Assuntos
Tomada de Decisões , Assistência Terminal , Humanos , Grupos Raciais , Incerteza , Cuidados Paliativos , Morte , Comunicação
5.
Ann Surg Oncol ; 29(9): 5759-5769, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-35608799

RESUMO

BACKGROUND: Delays between breast cancer diagnosis and surgery are associated with worsened survival. Delays are more common in urban-residing patients, although factors specific to surgical delays among rural and urban patients are not well understood. METHODS: We used a 100% sample of fee-for-service Medicare claims during 2007-2014 to identify 238,491 women diagnosed with early-stage breast cancer undergoing initial surgery and assessed whether they experienced biopsy-to-surgery intervals > 90 days. We employed multilevel regression to identify associations between delays and patient, regional, and surgeon characteristics, both in combined analyses and stratified by rurality of patient residence. RESULTS: Delays were more prevalent among urban patients (2.5%) than rural patients (1.9%). Rural patients with medium- or high-volume surgeons had lower odds of delay than patients with low-volume surgeons (odds ratio [OR] = 0.71, 95% confidence interval [CI] = 0.58-0.88; OR = 0.74, 95% CI = 0.61-0.90). Rural patients whose surgeon operated at ≥ 3 hospitals were more likely to experience delays (OR = 1.29, 95% CI = 1.01-1.64, Ref: 1 hospital). Patient driving times ≥ 1 h were associated with delays among urban patients only. Age, black race, Hispanic ethnicity, multimorbidity, and academic/specialty hospital status were associated with delays. CONCLUSIONS: Sociodemographic, geographic, surgeon, and facility factors have distinct associations with > 90-day delays to initial breast cancer surgery. Interventions to improve timeliness of breast cancer surgery may have disparate impacts on vulnerable populations by rural-urban status.


Assuntos
Neoplasias da Mama , Medicare , Idoso , Neoplasias da Mama/epidemiologia , Neoplasias da Mama/cirurgia , Feminino , Hispânico ou Latino , Humanos , Razão de Chances , População Rural , Estados Unidos/epidemiologia
6.
Breast Cancer Res Treat ; 189(1): 49-61, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34196902

RESUMO

PURPOSE: Breast cancer remains a prominent global disease affecting women worldwide despite the emergence of novel therapeutic regimens. Metastasis is responsible for most cancer-related deaths, and acquisition of a mesenchymal and migratory cancer cell phenotypes contributes to this devastating disease. The utilization of kinase targets in drug discovery have revolutionized the field of cancer research but despite impressive advancements in kinase-targeting drugs, a large portion of the human kinome remains understudied in cancer. NEK5, a member of the Never-in-mitosis kinase family, is an example of such an understudied kinase. Here, we characterized the function of NEK5 in breast cancer. METHODS: Stably overexpressing NEK5 cell lines (MCF7) and shRNA knockdown cell lines (MDA-MB-231, TU-BcX-4IC) were utilized. Cell morphology changes were evaluated using immunofluorescence and quantification of cytoskeletal components. Cell proliferation was assessed by Ki-67 staining and transwell migration assays tested cell migration capabilities. In vivo experiments with murine models were necessary to demonstrate NEK5 function in breast cancer tumor growth and metastasis. RESULTS: NEK5 activation altered breast cancer cell morphology and promoted cell migration independent of effects on cell proliferation. NEK5 overexpression or knockdown does not alter tumor growth kinetics but promotes or suppresses metastatic potential in a cell type-specific manner, respectively. CONCLUSION: While NEK5 activity modulated cytoskeletal changes and cell motility, NEK5 activity affected cell seeding capabilities but not metastatic colonization or proliferation in vivo. Here we characterized NEK5 function in breast cancer systems and we implicate NEK5 in regulating specific steps of metastatic progression.


Assuntos
Neoplasias da Mama , Quinases Relacionadas a NIMA , Animais , Neoplasias da Mama/genética , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Transição Epitelial-Mesenquimal , Feminino , Humanos , Camundongos , Quinases Relacionadas a NIMA/genética , Fenótipo , RNA Interferente Pequeno
7.
Anticancer Drugs ; 31(8): 759-775, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32796402

RESUMO

Breast cancer affects women globally; the majority of breast cancer-related mortalities are due to metastasis. Acquisition of a mesenchymal phenotype has been implicated in the progression of breast cancer cells to an invasive, metastatic state. Triple-negative breast cancer (TNBC) subtypes have high rates of metastases, recurrence, and have poorer prognoses compared to other breast cancer types, partially due to lack of commonly targeted receptors. Kinases have diverse and pivotal functions in metastasis in TNBC, and discovery of new kinase targets for TNBC is warranted. We previously used a screening approach to identify intermediate-synthesis nonpotent, nonselective small-molecule inhibitors from the Published Kinase Inhibitor Set that reversed the mesenchymal phenotype in TNBC cells. Two of these inhibitors (GSK346294A and GSK448459A) are structurally similar, but have unique kinase activity profiles and exhibited differential biologic effects on TNBC cells, specifically on epithelial-to-mesenchymal transition (EMT). Here, we further interrogate these effects and compare activity of these inhibitors on transwell migration, gene (qRT-PCR) and protein (western blot) expressions, and cancer stem cell-like behavior. We incorporated translational patient-derived xenograft models in these studies, and we focused on the lead inhibitor hit, GSK346294A, to demonstrate the utility of our comparative analysis as a screening modality to identify novel kinase targets and signaling pathways to pursue in TNBC. This study introduces a new method for discovering novel kinase targets that reverse the EMT phenotype; this screening approach can be applied to all cancer types and is not limited to breast cancer.


Assuntos
Biomarcadores Tumorais/metabolismo , Neoplasias Pulmonares/tratamento farmacológico , Células-Tronco Neoplásicas/efeitos dos fármacos , Inibidores de Proteínas Quinases/farmacologia , Transdução de Sinais/efeitos dos fármacos , Bibliotecas de Moléculas Pequenas/farmacologia , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Animais , Apoptose , Proliferação de Células , Transição Epitelial-Mesenquimal , Feminino , Humanos , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/secundário , Camundongos , Estrutura Molecular , Células-Tronco Neoplásicas/metabolismo , Células-Tronco Neoplásicas/patologia , Fosforilação , Neoplasias de Mama Triplo Negativas/metabolismo , Neoplasias de Mama Triplo Negativas/patologia , Células Tumorais Cultivadas , Ensaios Antitumorais Modelo de Xenoenxerto
8.
BMC Palliat Care ; 19(1): 136, 2020 Aug 27.
Artigo em Inglês | MEDLINE | ID: mdl-32854691

RESUMO

BACKGROUND: A critical barrier to improving the quality of end-of-life (EOL) cancer care is our lack of understanding of the mechanisms underlying variation in EOL treatment intensity. This study aims to fill this gap by identifying 1) organizational and provider practice norms at major US cancer centers, and 2) how these norms influence provider decision making heuristics and patient expectations for EOL care, particularly for minority patients with advanced cancer. METHODS: This is a multi-center, qualitative case study at six National Comprehensive Cancer Network (NCCN) and National Cancer Institute (NCI) Comprehensive Cancer Centers. We will theoretically sample centers based upon National Quality Forum (NQF) endorsed EOL quality metrics and demographics to ensure heterogeneity in EOL intensity and region. A multidisciplinary team of clinician and non-clinician researchers will conduct direct observations, semi-structured interviews, and artifact collection. Participants will include: 1) cancer center and clinical service line administrators; 2) providers from medical, surgical, and radiation oncology; palliative or supportive care; intensive care; hospital medicine; and emergency medicine who see patients with cancer and have high clinical practice volume or high local influence (provider interviews and observations); and 3) adult patients with metastatic solid tumors and whom the provider would not be surprised if they died in the next 12 months and their caregivers (patient and caregiver interviews). Leadership interviews will probe about EOL institutional norms and organization. We will observe inpatient and outpatient care for two weeks. Provider interviews will use vignettes to probe explicit and implicit motivations for treatment choices. Semi-structured interviews with patients near EOL, or their family members and caregivers will explore past, current, and future decisions related to their cancer care. We will import transcribed field notes and interviews into Dedoose software for qualitative data management and analysis, and we will develop and apply a deductive and inductive codebook to the data. DISCUSSION: This study aims to improve our understanding of organizational and provider practice norms pertinent to EOL care in U.S. cancer centers. This research will ultimately be used to inform a provider-oriented intervention to improve EOL care for racial and ethnic minority patients with advanced cancer. TRIAL REGISTRATION: Clinicaltrials.gov ; NCT03780816 ; December 19, 2018.


Assuntos
Institutos de Câncer/normas , Protocolos Clínicos , Qualidade da Assistência à Saúde/normas , Assistência Terminal/normas , Institutos de Câncer/organização & administração , Humanos , Entrevistas como Assunto/métodos , Pesquisa Qualitativa
9.
Breast Cancer Res Treat ; 174(3): 759-767, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30607634

RESUMO

PURPOSE: Increasingly epidemiological cohorts are being linked to claims data to provide rich data for healthcare research. These cohorts tend to be different than the general United States (US) population. We will analyze healthcare utilization of Nurses' Health Study (NHS) participants to determine if studies of newly diagnosed incident early-stage breast cancer can be generalized to the broader US Medicare population. METHODS: Analytic cohorts of fee-for-service NHS-Medicare-linked participants and a 1:13 propensity-matched SEER-Medicare cohort (SEER) with incident breast cancer in the years 2007-2011 were considered. Screening leading to, treatment-related, and general utilization in the year following early-stage breast cancer diagnosis were determined using Medicare claims data. RESULTS: After propensity matching, NHS and SEER were statistically balanced on all demographics. NHS and SEER had statistically similar rates of treatments including chemotherapy, breast-conserving surgery, mastectomy, and overall radiation use. Rates of general utilization include those related to hospitalizations, total visits, and emergency department visits were also balanced between the two groups. Total spending in the year following diagnosis were statistically equivalent for NHS and SEER ($36,180 vs. $35,399, p = 0.70). CONCLUSIONS: NHS and the general female population had comparable treatment and utilization patterns following diagnosis of early-stage incident breast cancers with the exception of type of radiation therapy received. This study provides support for the larger value of population-based cohorts in research on healthcare costs and utilization in breast cancer.


Assuntos
Neoplasias da Mama/terapia , Planos de Pagamento por Serviço Prestado/organização & administração , Medicare/estatística & dados numéricos , Enfermeiras e Enfermeiros/estatística & dados numéricos , Idoso , Idoso de 80 Anos ou mais , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/patologia , Planos de Pagamento por Serviço Prestado/estatística & dados numéricos , Feminino , Seguimentos , Custos de Cuidados de Saúde , Humanos , Revisão da Utilização de Seguros , Estadiamento de Neoplasias , Aceitação pelo Paciente de Cuidados de Saúde , Pontuação de Propensão , Programa de SEER , Estados Unidos
10.
Med Care ; 56(12): e83-e89, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-29334524

RESUMO

BACKGROUND: In an effort to overcome quality and cost constraints inherent in population-based research, diverse data sources are increasingly being combined. In this paper, we describe the performance of a Medicare claims-based incident cancer identification algorithm in comparison with observational cohort data from the Nurses' Health Study (NHS). METHODS: NHS-Medicare linked participants' claims data were analyzed using 4 versions of a cancer identification algorithm across 3 cancer sites (breast, colorectal, and lung). The algorithms evaluated included an update of the original Setoguchi algorithm, and 3 other versions that differed in the data used for prevalent cancer exclusions. RESULTS: The algorithm that yielded the highest positive predictive value (PPV) (0.52-0.82) and κ statistic (0.62-0.87) in identifying incident cancer cases utilized both Medicare claims and observational cohort data (NHS) to remove prevalent cases. The algorithm that only used NHS data to inform the removal of prevalent cancer cases performed nearly equivalently in statistical performance (PPV, 0.50-0.79; κ, 0.61-0.85), whereas the version that used only claims to inform the removal of prevalent cancer cases performed substantially worse (PPV, 0.42-0.60; κ, 0.54-0.70), in comparison with the dual data source-informed algorithm. CONCLUSIONS: Our findings suggest claims-based algorithms identify incident cancer with variable reliability when measured against an observational cohort study reference standard. Self-reported baseline information available in cohort studies is more effective in removing prevalent cancer cases than are claims data algorithms. Use of claims-based algorithms should be tailored to the research question at hand and the nature of available observational cohort data.


Assuntos
Neoplasias da Mama/epidemiologia , Estudos de Coortes , Neoplasias Colorretais/epidemiologia , Armazenamento e Recuperação da Informação/métodos , Revisão da Utilização de Seguros/estatística & dados numéricos , Neoplasias Pulmonares/epidemiologia , Idoso , Idoso de 80 Anos ou mais , Algoritmos , Feminino , Humanos , Medicare , Prevalência , Estados Unidos/epidemiologia
11.
Breast Cancer Res Treat ; 162(3): 409-417, 2017 04.
Artigo em Inglês | MEDLINE | ID: mdl-28160158

RESUMO

PURPOSE: Breast conservation therapy (BCT) for early-stage breast cancer involves lumpectomy followed by whole breast radiotherapy, which can involve either standard fractionation (SRT) or accelerated fractionation (ART). This systematic review and meta-analysis was performed to determine whether any benefit exists for ART or SRT. MATERIALS AND METHODS: We searched MEDLINE (1966-2014), all seven databases of the Cochrane Library (1968-2014), EMBASE (1974-2014), clinicaltrials.gov, ISRCTN, WHO ICTRP, and meeting abstracts in the Web of Science Core Collection (1900-2014). RCTs comparing SRT to ART among women undergoing BCT with stage T1-T2 and/or N1 breast cancer or carcinoma in situ were included. Follow-up was 30 days for acute toxicity, or three years for disease control and late toxicity. RESULTS: 13 trials with 8189 participants were included. No differences were observed in local failure (n = 7 trials; RR 0.97; 95% CI 0.78-1.19, I 2 = 0%), locoregional failure, (n = 8 trials; RR 0.86; 95% CI 0.63-1.16, I 2 = 0%), or survival (n = 4 trials; RR 1.00; 95% CI 0.85-1.17, I 2 = 0%). ART was associated with significantly less acute toxicity (n = 5 trials; RR 0.36; 95% CI 0.21-0.62, I 2 = 20%), but no difference in late cosmesis (RR 0.95; 95% CI 0.81-1.12, I 2 = 54%). CONCLUSIONS: ART use does not reduce disease control or worsen long-term cosmetic outcome, and may decrease the risk of acute radiation toxicity as compared to SRT.


Assuntos
Neoplasias da Mama/patologia , Neoplasias da Mama/radioterapia , Hipofracionamento da Dose de Radiação , Neoplasias da Mama/mortalidade , Feminino , Humanos , Estadiamento de Neoplasias , Razão de Chances , Viés de Publicação , Radioterapia Adjuvante , Ensaios Clínicos Controlados Aleatórios como Assunto , Resultado do Tratamento
12.
Bioorg Med Chem Lett ; 26(14): 3216-3219, 2016 07 15.
Artigo em Inglês | MEDLINE | ID: mdl-27261181

RESUMO

A series of compounds in which various halogen substituents were incorporated into a phenyl ring of a tris-(phenylalkyl)amine scaffold, was synthesized and evaluated for affinity to h5-HT2 receptors. In general, all compounds were found to have good affinity for the 5-HT2B receptor and were selective over 5-HT2A and 5-HT2C receptors. Compound 9i was the most selective compound in this study and is the highest affinity 5-HT2B receptor ligand bearing a tris-(phenylalkyl)amine scaffold to date.


Assuntos
Aminas/farmacologia , Receptor 5-HT2B de Serotonina/metabolismo , Aminas/síntese química , Aminas/química , Relação Dose-Resposta a Droga , Humanos , Ligantes , Estrutura Molecular , Receptor 5-HT2A de Serotonina/metabolismo , Receptor 5-HT2C de Serotonina/metabolismo , Relação Estrutura-Atividade
13.
Bioorg Med Chem Lett ; 25(17): 3451-4, 2015 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-26227772

RESUMO

A group of aporphine alkaloids related to (±)-nantenine (1) and bearing a C4 phenyl and various C1 or N-substituents, was synthesized and evaluated for affinity to h5-HT receptors. In general, unlike nantenine, the analogs lack affinity for the h5-HT(2A) receptor and other 5-HT receptors but bind selectively to the h5-HT(2B) receptor. With regards to 5-HT(2B) affinity, there appears to be a low tolerance for bulky C1 or N-substituents when the C4 phenyl moiety is present. Compound 5a had the highest 5-HT(2B) affinity of the compounds tested, was found to be an antagonist and is selective vs other CNS receptors.


Assuntos
Aporfinas/química , Receptor 5-HT2A de Serotonina/metabolismo , Antagonistas do Receptor 5-HT2 de Serotonina/química , Aporfinas/farmacologia , Estrutura Molecular , Antagonistas do Receptor 5-HT2 de Serotonina/farmacologia , Relação Estrutura-Atividade
14.
Bioorg Med Chem Lett ; 25(22): 5102-6, 2015 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-26475518

RESUMO

A series of C1 aporphine analogs related to compound 5 and that contain substituted allylic, alkynyl, nitrile, ester and benzyl groups was synthesized and evaluated for affinity at h5HT2A and α1A receptors in functional activity assays that measure calcium release. The presence of branched allylic substituent groups diminished affinity for the h5HT2A receptor. Likewise, the alkynyl, nitrile and ester derivatives evaluated displayed lower 5-HT2A receptor affinity as compared to 5. Hydrophobic, steric and electronic effects impact the affinity of p-substituted benzyl derivatives 8i-8k but in different ways. High hydrophobicity and size favor 5-HT2A affinity whereas, high electronegativity disfavors 5-HT2A affinity. p-Bromobenzyl analog 8k was identified as a 5-HT2A receptor selective ligand, with the highest 5-HT2A receptor affinity of any aporphine known to date. Most of the other analogs were selective for the 5-HT2A versus the α1A receptor. ChemScore binding energies from docking studies correlated qualitatively with the observed trends in affinity for 8i-8k, although the binding energies were not well differentiated quantitatively.


Assuntos
Aporfinas/farmacologia , Compostos Heterocíclicos de 4 ou mais Anéis/farmacologia , Agonistas do Receptor 5-HT2 de Serotonina/farmacologia , Antagonistas de Receptores Adrenérgicos alfa 1/síntese química , Antagonistas de Receptores Adrenérgicos alfa 1/farmacologia , Aporfinas/síntese química , Compostos Heterocíclicos de 4 ou mais Anéis/síntese química , Humanos , Interações Hidrofóbicas e Hidrofílicas , Ligantes , Simulação de Acoplamento Molecular , Receptor 5-HT2A de Serotonina/metabolismo , Agonistas do Receptor 5-HT2 de Serotonina/síntese química , Relação Estrutura-Atividade
15.
Bioorg Med Chem Lett ; 24(7): 1664-7, 2014 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-24630561

RESUMO

A set of aporphine analogs related to nantenine was evaluated for antagonist activity at 5-HT2A and α1A adrenergic receptors. With regards to 5-HT2A receptor antagonism, a C2 allyl group is detrimental to activity. The chiral center of nantenine is not important for 5-HT2A antagonist activity, however the N6 nitrogen atom is a critical feature for 5-HT2A antagonism. Compound 12b was the most potent 5-HT2A aporphine antagonist identified in this study and has similar potency to previously identified aporphine antagonists 2 and 3. The ring A and N6 modifications examined were detrimental to α1A antagonism. A slight eutomeric preference for the R enantiomer of nantenine was observed in relation to α1A antagonism.


Assuntos
Aporfinas/farmacologia , Receptor 5-HT2A de Serotonina/metabolismo , Antagonistas do Receptor 5-HT2 de Serotonina/farmacologia , Aporfinas/síntese química , Aporfinas/química , Relação Dose-Resposta a Droga , Humanos , Estrutura Molecular , Antagonistas do Receptor 5-HT2 de Serotonina/síntese química , Antagonistas do Receptor 5-HT2 de Serotonina/química , Relação Estrutura-Atividade
16.
Cureus ; 16(7): e65207, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-39176344

RESUMO

Androgen deprivation therapy (ADT) is one of the effective treatment methods for prostate cancer, often used with radiation therapy. Among the key ADT agents is leuprolide, a synthetic gonadotropin-releasing hormone agonist, which effectively suppresses testosterone production which is a requisite for the growth and division of prostate cancer cells. However, leuprolide is associated with several well-known side effects and less common dermatological reactions. In this case, we present an 80-year-old male patient with stage IIB prostate cancer who developed diffuse maculopapular dermatitis following leuprolide acetate ADT. The patient first experienced mild dermatitis following the fifth monthly 7.5 mg leuprolide injection before it developed into a general body rash after six injections. The dermatitis manifested on the patient's arms, thighs, calves, dorsum, and back of hands but sparing the abdomen, face, and neck. The pruritic dermatitis was managed successfully with a three-week course of prednisone which led to complete resolution without long-term sequelae. This case highlights the importance of recognizing and managing dermatological side effects associated with ADT. Clinicians should maintain an index of suspicion and act promptly when these side effects manifest. Systematic reporting and further research are essential to enhance patient safety and understanding of drug-related dermatological manifestations.

17.
Int J Radiat Oncol Biol Phys ; 120(1): 102-110, 2024 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-38490619

RESUMO

PURPOSE: Disparities in access to a multidisciplinary cancer consultation (MDCc) persist, and the role of physician relationships remains understudied. This study examined the extent to which multilevel factors, including patient characteristics and patient-sharing network measures reflecting the structure of physician relationships, are associated with an MDCc and receipt of stereotactic body radiation therapy versus surgery among patients with early-stage non-small cell lung cancer (NSCLC). METHODS AND MATERIALS: In this cross-sectional study, we analyzed Surveillance, Epidemiology, and End Results (SEER)-Medicare data for patients diagnosed with stage I-IIA NSCLC from 2016 to 2017. We assembled patient-sharing networks and identified cancer specialists who were locally unique for their specialty, herein referred to as linchpins. The proportion of linchpin cancer specialists for each hospital referral region (HRR) was calculated as a network-based measure of specialist scarcity. We used multilevel multinomial logistic regression to estimate associations between study variables and receipt of an MDCc and multilevel logistic regression to examine the relationship between patient receipt of an MDCc and initial treatment. RESULTS: Our study included 6120 patients with stage I-IIA NSCLC, of whom 751 (12.3%) received an MDCc, 1729 (28.3%) consulted only a radiation oncologist, 2010 (32.8%) consulted only a surgeon, and 1630 (26.6%) consulted neither specialist within 2 months of diagnosis. Compared with patients residing in an HRR with a low proportion of linchpin surgeons, those residing in an HRR with a high proportion of linchpin surgeons had a 2.99 (95% CI, 1.87-4.78) greater relative risk of consulting only a radiation oncologist versus receiving an MDCc and a 2.70 (95% CI, 1.68-4.35) greater relative risk of consulting neither specialist versus receiving an MDCc. Patients who received an MDCc were 5.32 times (95% CI, 4.27-6.63) more likely to receive stereotactic body radiation therapy versus surgery. CONCLUSIONS: Physician networks are associated with receipt of an MDCc and treatment, underscoring the potential for leveraging patient-sharing network analysis to improve access to lung cancer care.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Acessibilidade aos Serviços de Saúde , Disparidades em Assistência à Saúde , Neoplasias Pulmonares , Medicare , Radiocirurgia , Encaminhamento e Consulta , Programa de SEER , Humanos , Carcinoma Pulmonar de Células não Pequenas/terapia , Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma Pulmonar de Células não Pequenas/radioterapia , Neoplasias Pulmonares/terapia , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/radioterapia , Estados Unidos , Idoso , Masculino , Feminino , Encaminhamento e Consulta/estatística & dados numéricos , Disparidades em Assistência à Saúde/estatística & dados numéricos , Estudos Transversais , Acessibilidade aos Serviços de Saúde/estatística & dados numéricos , Idoso de 80 Anos ou mais , Radiocirurgia/estatística & dados numéricos , Estadiamento de Neoplasias , Equipe de Assistência ao Paciente
18.
JCO Oncol Pract ; 20(6): 787-796, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38386962

RESUMO

PURPOSE: Oncology outreach is a common strategy for extending cancer care to rural patients. However, a nationwide characterization of the traveling workforce that enables this outreach is lacking, and the extent to which outreach reduces travel burden for rural patients is unknown. METHODS: This cross-sectional study analyzed a rural (nonurban) subset of a 100% fee-for-service sample of 355,139 Medicare beneficiaries with incident breast, colorectal, and lung cancers. Surgical, medical, and radiation oncologists were linked to patients using Part B claims, and traveling oncologists were identified by observing hospital service area (HSA) transition patterns. We defined oncology outreach as the provision of cancer care by a traveling oncologist outside of their primary HSA. We used hierarchical gamma regression models to examine the separate associations between patient receipt of oncology outreach and one-way patient travel times to chemotherapy, radiotherapy, and surgery. RESULTS: On average, 9,935 of 39,960 oncologists conducted annual outreach, where 57.8% traveled with low frequency (0-1 outreach visits/mo), 21.1% with medium frequency (1-3 outreach visits/mo), and 21.1% with high frequency (>3 outreach visits/mo). Oncologists provided surgery, radiotherapy, and chemotherapy to 51,715, 27,120, and 5,874 rural beneficiaries, respectively, of whom 2.5%, 6.9%, and 3.6% received oncology outreach. Rural patients who received oncology outreach traveled 16% (95% CI, 11 to 21) and 11% (95% CI, 9 to 13) less minutes to chemotherapy and radiotherapy than those who did not receive oncology outreach, corresponding to expected one-way savings of 15.9 (95% CI, 15.5 to 16.4) and 11.9 (95% CI, 11.7 to 12.2) minutes, respectively. CONCLUSION: Our study introduces a novel claims-based approach for tracking the nationwide traveling oncology workforce and supports oncology outreach as an effective means for improving rural access to cancer care.


Assuntos
Viagem , Humanos , Estudos Transversais , Masculino , Feminino , Oncologia , Idoso , Neoplasias/terapia , Neoplasias/epidemiologia , População Rural , Estados Unidos/epidemiologia
19.
Tetrahedron ; 69(42)2013 Oct 21.
Artigo em Inglês | MEDLINE | ID: mdl-24187388

RESUMO

Oxa-Pictet-Spengler cyclization and microwave-assisted C-H arylation have been implemented as key steps in the synthesis of new isochroman heterocycles containing a 4,5,6a,7-tetrahydrodibenzo[de,g]chromene motif. These isochromans may be easily transformed to phenanthrene alkaloids via acidic cleavage of the isochroman ring and standard synthetic manipulations thereafter. The route described is attractive in that it provides access to two biologically interesting scaffolds in simple and high yielding synthetic steps.

20.
Learn Health Syst ; 7(3): e10353, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-37448458

RESUMO

Introduction: Healthcare systems are actively working to innovate their care delivery models, seeking to improve service quality, improve patient and provider satisfaction, and reduce cost. Methods: By critically evaluating our experiences to date, this article highlights challenges systems may face in the process of trying to redesign healthcare and offers insights on how to navigate hurdles. We identify barriers to-and ultimately approaches to promote-rapid, scalable, sustainable, and transformative care redesign. Results: Dedicated electronic health record IT and analytic support, and ongoing leadership engagement and communication, play a valuable role in enabling redesign efforts. Flexible, but guided, innovation support helps teams stay accountable and motivated, while accommodating new project needs and directions. Understanding the change ecosystem and evaluating and sharing outcomes on an ongoing basis, enables teams to adapt as needed. Facilitation and support help realize the value of diverse, engaged teams; novel approaches and techniques draw out innovative perspectives and promote creative thinking. Conclusions: Although not an exhaustive list of challenges or strategies to overcome them, we hope these insights will contribute to a culture of innovation and support other institutions in their healthcare redesign initiatives.

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