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OBJECTIVE: Globally, the number of older adults surviving cancer is anticipated to grow rapidly over the next decades. Cancer and its treatment can leave survivors with a myriad of challenges including physical changes which impact independence and quality of life. This project explored the relationship of income level with concerns and help-seeking for physical changes following treatment in older Canadian survivors of cancer. METHODS: A Canada-wide survey of community-dwelling survivors of cancer explored their experiences with survivorship care one to three years following completion of treatment. A secondary trend analysis examined the relationship of income with older adults' level of concern and help-seeking experiences regarding physical consequences they attributed to their cancer treatment. RESULTS: In total, 7,975 people aged 65 years and older who survived cancer responded to the survey, of whom 5,891 (73.9%) indicated annual household income. Prostate (31.3%), colorectal (22.7%) and breast (21.8%) cancer accounted for the majority of respondents. Of those who reported household income data, over 90% wrote about the impact of physical changes following treatment, their concerns about the changes, and whether they sought help for their concerns. The most frequently identified physical challenge was fatigue (63.7%). Older survivors with low annual household incomes of less than $CA25,000 reported the highest levels of concern about multiple physical symptoms. 25% or more of the survey respondents across all income levels reported difficulty finding assistance for their concerns about the physical challenges, especially in their local communities. CONCLUSION: Older survivors of cancer can experience a range of physical changes, amenable to intervention by physical therapy, yet experience challenges obtaining relevant help. Those with low income are more severely affected, even within a universal healthcare system. Financial assessment and tailored follow-up are recommended.
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Supervivientes de Cáncer , Neoplasias , Masculino , Humanos , Anciano , Calidad de Vida , Canadá/epidemiología , Neoplasias/diagnóstico , Neoplasias/epidemiología , Neoplasias/terapia , SobrevivientesRESUMEN
OBJECTIVE: To describe the treatment and outcome of a foal with a fresh allogenic cancellous bone graft after surgical debridement of a traumatic septic osteitis. ANIMAL: A neonatal Quarter Horse foal. STUDY DESIGN: Case report. METHODS: The foal sustained a traumatic laceration exposing the proximal third metatarsal bone. One week after surgical debridement and closure, radiographic signs of septic osteitis were noted along the physeal scar. The lesion was debrided, and antimicrobial therapy was implemented. The infection resolved but left a large defect in the metaphysis and epiphysis. Grafting was indicated to avoid pathologic fractures of the plantar and proximal cortices. Due to a discrepancy between defect size and the bone stock of the foal, an allogeneic cancellous bone graft was harvested from the dam's tuber coxae and used to fill the foal's defect. RESULTS: No adverse reactions to the graft were noted. After 1 month, the wound had healed. Radiographic examination was consistent with graft incorporation in the bone structure. The foal was sound at a walk and trot when examined at 6, 12, and 21 months. The bone's contour was even and its structure homogeneously radio dense. The surgical site of the mare healed without complications. CONCLUSION: Fresh allogenic cancellous bone grafting resulted in the healing of a large traumatic-septic bone defect in a foal, with an excellent functional and cosmetic outcome. For future use, compatibility testing should be considered prior to allogeneic bone grafting.
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Trasplante de Células Madre Hematopoyéticas , Enfermedades de los Caballos , Huesos Metatarsianos , Osteítis , Caballos , Animales , Femenino , Hueso Esponjoso/trasplante , Cicatriz/veterinaria , Metatarso , Osteítis/veterinaria , Epífisis , Trasplante de Células Madre Hematopoyéticas/veterinaria , Trasplante Óseo/veterinaria , Enfermedades de los Caballos/cirugíaRESUMEN
BACKGROUND: Audio recordings of oncology clinic discussions can help patients retain and understand information about their disease and treatment decisions. Access to this tool relies on acceptance of recordings by oncologists. This is the first study to evaluate experience and attitudes of oncologists toward patients recording clinic visits. METHODS: Medical, radiation, and surgicalâ¯oncologists from 5 US cancer centers and community affiliates were surveyed to evaluate clinicians'â¯experience, beliefs, and practices regarding patient-initiated recordings. RESULTS: Amongâ¯360â¯oncologists (69%â¯response rate), virtually all (93%) have experienced patients seeking to record visits. Although 75%â¯are comfortableâ¯with recording, 25% are uncomfortableâ¯and 56% report concerns ranging fromâ¯less thorough discussionsâ¯to legal liability. Most (85%) always agree when patients ask to record, butâ¯15% never or selectively allow recording.â¯Althoughâ¯51%â¯believe recordingâ¯isâ¯positive for the patient-physician relationship, a sizable minority report that it canâ¯lead to less detailed conversationsâ¯(28%) orâ¯avoidance of difficult topics, including prognosisâ¯(33%). Views did not vary based onâ¯subspecialty, practice setting, orâ¯geographicâ¯region, but older age and years in practice were associated with more positiveâ¯views of recording. The majority of clinicians (72%) desireâ¯institutional policies to govern guidelines about recordings. CONCLUSIONS: Most oncologists are comfortable with patient requests to record visits, but a sizable minority remain uncomfortable, and access toâ¯recordingâ¯varies solelyâ¯on physician preference. This difference in care delivery may benefit from institutional policies that promote access while addressing legitimate physician concerns over privacy and appropriate use of recordings.
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Oncología Médica , Oncólogos , Atención Ambulatoria , Humanos , Relaciones Médico-Paciente , Encuestas y CuestionariosRESUMEN
PURPOSE OF REVIEW: The purpose of this brief review is to highlight significant recent developments in survivorship research and care of older adults following cancer treatment. The aim is to provide insight into care and support needs of older adults during cancer survivorship as well as directions for future research. RECENT FINDINGS: The numbers of older adult cancer survivors are increasing globally. Increased attention to the interaction between age-related and cancer-related concerns before, during, and after cancer treatment is needed to optimize outcomes and quality of life among older adult survivors. Issues of concern to older survivors, and ones associated with quality of life, include physical and cognitive functioning and emotional well-being. Maintaining activities of daily living, given limitations imposed by cancer treatment and other comorbidities, is of primary importance to older survivors. Evidence concerning the influence of income and rurality, experiences in care coordination and accessing services, and effectiveness of interventions remains scant for older adults during survivorship. There is a clear need for further research relating to tailored intervention and health care provider knowledge and education. Emerging issues, such as the use of medical assistance in dying, must be considered in this population.
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Supervivientes de Cáncer , Neoplasias , Actividades Cotidianas , Anciano , Supervivientes de Cáncer/psicología , Humanos , Neoplasias/psicología , Neoplasias/terapia , Calidad de Vida/psicología , SupervivenciaRESUMEN
PURPOSE: We sought to investigate the patient and physician approaches to malignant bowel obstruction (MBO) due to recurrent gynecologic cancer by (1) comparing patient and physician expectations and priorities during a new MBO diagnosis, and (2) highlighting factors that facilitate patient-doctor communication. METHODS: Patients were interviewed about their experience during an admission for MBO, and physicians were interviewed about their general approach towards MBO. Interviews were analyzed for themes using QDAMiner qualitative analysis software. The analysis utilized the framework analysis and used both predetermined themes and those that emerged from the data. RESULTS: We interviewed 14 patients admitted with MBO from recurrent gynecologic cancer and 15 gynecologic oncologists. We found differences between patients and physicians regarding plans for next chemotherapy treatments, foremost priorities, communication styles, and need for end-of-life discussions. Both patients and physicians felt that patient-physician communication was improved in situations of trust, understanding patient preferences, corroboration of information, and increased time spent with patients during and before the MBO. CONCLUSION: Gaps in patient-physician communication could be targeted to improve the patient experience and physician counseling during a difficult diagnosis. Our findings emphasize a need for patient-physician discussions to focus on expectations for future cancer-directed treatments, support for patients at home with home health or hospice level support in line with their wishes, and acknowledgement of uncertainty while providing direct information about the MBO diagnosis.
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Neoplasias de los Genitales Femeninos , Obstrucción Intestinal , Oncólogos , Comunicación , Femenino , Neoplasias de los Genitales Femeninos/complicaciones , Humanos , Obstrucción Intestinal/etiología , Obstrucción Intestinal/terapia , Cuidados Paliativos , Relaciones Médico-PacienteRESUMEN
BACKGROUND: Pre-treatment tumour-associated lymphocytes (TILs) and stromal lymphocytes (SLs) are independent predictive markers of future pathological complete response (pCR) in HER2-positive breast cancer. Whilst studies have correlated baseline lymphocyte levels with subsequent pCR, few have studied the impact of neoadjuvant therapy on the immune environment. METHODS: We performed TIL analysis and T-cell analysis by IHC on the pretreatment and 'On-treatment' samples from patients recruited on the Phase-II TCHL (NCT01485926) clinical trial. Data were analysed using the Wilcoxon signed-rank test and the Spearman rank correlation. RESULTS: In our sample cohort (n = 66), patients who achieved a pCR at surgery, post-chemotherapy, had significantly higher counts of TILs (p = 0.05) but not SLs (p = 0.08) in their pre-treatment tumour samples. Patients who achieved a subsequent pCR after completing neo-adjuvant chemotherapy had significantly higher SLs (p = 9.09 × 10-3) but not TILs (p = 0.1) in their 'On-treatment' tumour biopsies. In a small cohort of samples (n = 16), infiltrating lymphocyte counts increased after 1 cycle of neo-adjuvant chemotherapy only in those tumours of patients who did not achieve a subsequent pCR. Finally, reduced CD3 + (p = 0.04, rho = 0.60) and CD4 + (p = 0.01, rho = 0.72) T-cell counts in 'On-treatment' biopsies were associated with decreased residual tumour content post-1 cycle of treatment; the latter being significantly associated with increased likelihood of subsequent pCR (p < 0.01). CONCLUSIONS: The immune system may be 'primed' prior to neoadjuvant treatment in those patients who subsequently achieve a pCR. In those patients who achieve a pCR, their immune response may return to baseline after only 1 cycle of treatment. However, in those who did not achieve a pCR, neo-adjuvant treatment may stimulate lymphocyte influx into the tumour.
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Neoplasias de la Mama , Terapia Neoadyuvante , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/genética , Femenino , Humanos , Linfocitos , Linfocitos Infiltrantes de Tumor , Pronóstico , Receptor ErbB-2/genéticaRESUMEN
Patients with cancer face many difficult decisions and encounter many clinical situations that undermine decisional capacity. For this reason, assessing decision-making capacity should be thought of at every medical encounter. The culmination of variable disease trajectories, following patients to the end of life, use of high-risk treatments, and other weighty personal decisions require attention to patients' ability to engage in decisions. Oncologists develop meaningful relationships with their patients. This familiarity may lead to forgoing the process of diligently assessing a patient's cognitive ability and/or decisional capacity when important decisions need to be made. While the process may feel like it takes place spontaneously, many subtle and overt details are involved with the decisions around cancer care that require pointed questioning and probing. Thus, there are many ways to fall short in determining decisional capacity. Clinicians are inconsistent in their decisional capacity determinations and generally assume more decisional capacity than the patient has. Consult and referral services such as ethics and psychiatry can help with treatment decisions and with assessing underlying psychosocial and psychiatric conditions. Decisional capacity may fluctuate and requires a variable amount of decisional ability depending on the clinical situation; hence, it is time-specific and decision-specific. This review is intended to provide a summary of key components of decisional capacity while highlighting areas in need of clinical refinement.
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Toma de Decisiones/ética , Competencia Mental/psicología , Neoplasias/psicología , Neoplasias/terapia , Participación del Paciente/psicología , Humanos , Consentimiento Informado/ética , Consentimiento Informado/normas , Neoplasias/diagnóstico , Oncólogos/ética , Relaciones Médico-Paciente/ética , Derivación y Consulta/normas , Cuidado Terminal/ética , Cuidado Terminal/normasRESUMEN
The abnormal deposition of calcium within renal parenchyma, termed nephrocalcinosis, frequently occurs as a result of impaired renal calcium handling. It is closely associated with renal stone formation (nephrolithiasis) as elevated urinary calcium levels (hypercalciuria) are a key common pathological feature underlying these clinical presentations. Although monogenic causes of nephrocalcinosis and nephrolithiasis are rare, they account for a significant disease burden with many patients developing chronic or end-stage renal disease. Identifying underlying genetic mutations in hereditary cases of nephrocalcinosis has provided valuable insights into renal tubulopathies that include hypercalciuria within their varied phenotypes. Genotypes affecting other enzyme pathways, including vitamin D metabolism and hepatic glyoxylate metabolism, are also associated with nephrocalcinosis. As the availability of genetic testing becomes widespread, we cannot be imprecise in our approach to nephrocalcinosis. Monogenic causes of nephrocalcinosis account for a broad range of phenotypes. In cases such as Dent disease, supportive therapies are limited, and early renal replacement therapies are necessitated. In cases such as renal tubular acidosis, a good renal prognosis can be expected providing effective treatment is implemented. It is imperative we adopt a precision-medicine approach to ensure patients and their families receive prompt diagnosis, effective, tailored treatment and accurate prognostic information.
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Heterogeneidad Genética , Mutación , Nefrocalcinosis/genética , Fenotipo , Adenilil Ciclasas/genética , Animales , Claudinas/genética , Humanos , Proteínas de Transporte de Membrana/genética , Nefrocalcinosis/patología , Receptores Sensibles al Calcio/genética , Vitamina D3 24-Hidroxilasa/genéticaRESUMEN
BACKGROUND: As scientific techniques evolve, historical informed consent forms may inadequately address modern research proposals, leading to ethical questions regarding research with archived biospecimens. SUBJECTS, MATERIALS, AND METHODS: We conducted focus groups among patients with cancer recruited from Massachusetts General Hospital to explore views on medical research, biobanking, and scenarios based on real biospecimen research dilemmas. Our multidisciplinary team developed a structured focus group guide, and all groups were recorded and transcribed. Transcripts were coded for themes by two independent investigators using NVivo software. RESULTS: Across five focus groups with 21 participants, we found that most participants were supportive of biobanks and use of their own tissue to advance scientific knowledge. Many favor allowing research beyond the scope of the original consent to proceed if recontact is impossible. However, participants were not comfortable speaking for other patients who may oppose research beyond the original consent. This was viewed as a potential violation of participants' rights or interests. Participants were also concerned with a "slippery slope" and potential scientific abuse if research were permitted without adherence to original consent. There was strong support for recontact and reconsent when possible and for the concept of broad consent at the time of tissue collection. CONCLUSION: Our participants support use of their tissue to advance research and generally support any productive scientific approach. However, in the absence of broad initial consent, when recontact is impossible, a case-by-case decision must be made regarding a proposal's potential benefits and harms. Many participants support broad use of their tissue, but a substantial minority object to use beyond the original consent. IMPLICATIONS FOR PRACTICE: For prospective studies collecting tissue for future research, investigators should consider seeking broad consent, to allow for evolution of research questions and methods. For studies using previously collected tissues, researchers should attempt recontact and reconsent for research aims or methods beyond the scope of the original consent. When reconsent is not possible, a case-by-case decision must be made, weighing the scientific value of the biobank, potential benefits of the proposed research, and the likelihood and nature of risks to participants and their welfare interests. This study's data suggest that many participants support broad use of their tissue and prefer science to move forward.
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Bancos de Muestras Biológicas/normas , Neoplasias/fisiopatología , Bancos de Tejidos/normas , Femenino , Grupos Focales , Humanos , MasculinoRESUMEN
Primate lentiviruses, including the human and simian immunodeficiency viruses (HIV and SIV), produce infections marked by persistent, ongoing viral replication. This occurs despite the presence of virus-specific adaptive immune responses, including antibodies targeting the viral envelope glycoprotein (Env), and evolution of antibody-escape variants is a well-documented feature of lentiviral infection. Here, we examined the evolutionary dynamics of the SIV env gene during early infection (≤29 weeks postinfection) in a cohort of four SIVmac251-infected rhesus macaques. We tracked env evolution during acute and early infection using frequent sampling and ultradeep sequencing of viral populations, capturing a transmission bottleneck and the subsequent reestablishment of Env diversity. A majority of changes in the gp120 subunit mapped to two short clusters, one in the first variable region (V1) and one in V4, while most changes in the gp41 subunit appeared in the cytoplasmic domain. Variation in V1 was dominated by short duplications and deletions of repetitive sequence, while variation in V4 was marked by short in-frame deletions and closely overlapping substitutions. The most common substitutions in both patches did not alter viral replicative fitness when tested using a highly sensitive, deep-sequencing-based competition assay. Our results, together with the observation that very similar or identical patterns of sequence evolution also occur in different macaque species infected with related but divergent strains of SIV, suggest that resistance to early, strain-specific anti-Env antibodies is the result of temporally and mutationally predictable pathways of escape that occur during the early stages of infection.IMPORTANCE The envelope glycoprotein (Env) of primate lentiviruses mediates entry by binding to host cell receptors followed by fusion of the viral membrane with the cell membrane. The exposure of Env complexes on the surface of the virion results in targeting by antibodies, leading to selection for virus escape mutations. We used the SIV/rhesus macaque model to track in vivo evolution of variation in Env during acute/early infection in animals with and without antibody responses to Env, uncovering remarkable variation in animals with antibody responses within weeks of infection. Using a deep-sequencing-based fitness assay, we found substitutions associated with antibody escape had little to no effect on inherent replicative capacity. The ability to readily propagate advantageous changes that incur little to no replicative fitness costs may be a mechanism to maintain continuous replication under constant immune selection, allowing the virus to persist for months to years in the infected host.
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Anticuerpos Antivirales , Productos del Gen env/inmunología , Secuenciación de Nucleótidos de Alto Rendimiento , Síndrome de Inmunodeficiencia Adquirida del Simio/genética , Síndrome de Inmunodeficiencia Adquirida del Simio/inmunología , Virus de la Inmunodeficiencia de los Simios/inmunología , Animales , Anticuerpos Antivirales/genética , Anticuerpos Antivirales/inmunología , Macaca mulattaRESUMEN
CD19-targeted chimeric antigen receptor (CAR) T-cells (CAR19s) show remarkable efficacy in the treatment of relapsed/refractory acute lymphocytic leukemia and Non-Hodgkin's lymphoma. However, the use of CAR T-cell therapy against CD19-negative hematological cancers and solid tumors has been challenging. We propose CD19-fusion proteins (CD19-FPs) to leverage the benefits of CAR19s while retargeting this validated cellular therapy to alternative tumor antigens. We demonstrate the ability of a fusion of CD19 extracellular domain (ECD) and a human epidermal growth factor receptor 2 (HER2) single-chain antibody fragment to retarget CAR19s to kill HER2+ CD19- tumor cells. To enhance the modularity of this technology, we engineered a more robust CD19 ECD via deep mutational scanning with yeast display and flow cytometric selections for improved protease resistance and anti-CD19 antibody binding. These enhanced CD19 ECDs significantly increase, and in some cases recover, fusion protein expression while maintaining target antigen affinity. Importantly, CD19-FPs retarget CAR19s to kill tumor cells expressing multiple distinct antigens, including HER2, CD20, EGFR, BCMA, and Clec12A as N- or C-terminal fusions and linked to both antibody fragments and fibronectin ligands. This study provides fundamental insights into CD19 sequence-function relationships and defines a flexible and modular platform to retarget CAR19s to any tumor antigen.
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Antígenos CD19/metabolismo , Inmunoterapia Adoptiva/métodos , Neoplasias/terapia , Proteínas Recombinantes de Fusión/metabolismo , Anticuerpos de Cadena Única/metabolismo , Linfocitos T/inmunología , Antígenos CD19/genética , Antígenos CD19/inmunología , Antígenos de Neoplasias/inmunología , Línea Celular Tumoral , Células HEK293 , Humanos , Mutagénesis , Neoplasias/inmunología , Neoplasias/patología , Dominios Proteicos/genética , Ingeniería de Proteínas , Receptor ErbB-2/antagonistas & inhibidores , Receptores Quiméricos de Antígenos/inmunología , Receptores Quiméricos de Antígenos/metabolismo , Proteínas Recombinantes de Fusión/genética , Proteínas Recombinantes de Fusión/inmunología , Anticuerpos de Cadena Única/genética , Anticuerpos de Cadena Única/inmunología , Linfocitos T/metabolismo , Linfocitos T/trasplanteRESUMEN
BACKGROUND: Electronic health records are being adopted due to numerous potential benefits. This requires the development of objective metrics to characterize morbidity, comparable to studies performed in centers without an electronic health record. We outline the development of an electronic version of the postoperative morbidity score for integration into our electronic health record. METHODS: Twohundred and three frail patients who underwent elective surgery were reviewed. We retrospectively defined postoperative morbidity score on postoperative day 3. We also recorded potential electronic surrogates for morbidities that could not be easily extracted in an objective format. We compared discriminative capability (area under the receiver operator curve) for patients having prolonged length of stay or complex discharge requirements. RESULTS: One hundred thirty-nine patients (68%) had morbidity in ≥1 postoperative morbidity score domain. Initial electronic surrogates were overly sensitive, identifying 173 patients (84%) as having morbidity. We refined our definitions using backward logistic regression against "gold-standard" postoperative morbidity score. The final electronic postoperative morbidity score differed from the initial version in its definition of cardiac and neurological morbidity. There was no significant difference in the discriminative capability between electronic postoperative morbidity score and postoperative morbidity score for either outcome (area under the receiver operator curve: 0.66 vs 0.66 for complex discharge requirement, area under the receiver operator curve: 0.66 vs 0.67 for a prolonged length of stay; P> .05 for both). Patients with postoperative morbidity score or electronic postoperative morbidity score-defined morbidity on day 3 had increased risk of prolonged length of stay (P < .001 for both). CONCLUSIONS: We present a variant of postoperative morbidity score based on objective electronic metrics. Discriminative performance appeared comparable to gold-standard definitions for discharge outcomes. Electronic postoperative morbidity score may allow characterization of morbidity within our electronic health record, but further study is required to assess external validity.
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Técnicas de Apoyo para la Decisión , Procedimientos Quirúrgicos Electivos/efectos adversos , Registros Electrónicos de Salud , Fragilidad/complicaciones , Complicaciones Posoperatorias/etiología , Factores de Edad , Anciano , Anciano de 80 o más Años , Femenino , Anciano Frágil , Fragilidad/diagnóstico , Humanos , Tiempo de Internación , Masculino , Complicaciones Posoperatorias/terapia , Valor Predictivo de las Pruebas , Reproducibilidad de los Resultados , Estudios Retrospectivos , Medición de Riesgo , Factores de Riesgo , Factores de Tiempo , Resultado del TratamientoRESUMEN
BACKGROUND: This study explores whether externalizing religious and spiritual beliefs is associated with advanced-stage colon cancer at initial oncology presentation and whether this association is stronger for blacks than for whites. METHODS: Patients who had newly diagnosed, invasive colon cancer were recruited at 9 sites in the Chicago metropolitan area. Eligible patients were non-Hispanic white or black, ages 30 to 79 years, and diagnosed with a primary invasive colon cancer. Patients were interviewed on prior screening and diagnosis. Social and attitudinal constructs were measured, including the God Locus of Health Control (GLHC) and Religious Problem Solving. The final response rate was 52% and included 407 patients. RESULTS: The median age was 59 years (range, 30-79 years), and 51% of participants were black. Cancer stage was available for 389 (96%) patients and was divided between late stage (stages III-IV; 60%) and early stage (stages I-II; 40%). Multivariate analysis indicated that patients in the highest tertile of scores on the GLHC were more likely have an advanced stage of disease at presentation (odds ratio, 2.14; 95% confidence interval, 1.00-4.59; P = .05) compared with those in the lowest tertile. No significant interaction was identified between race and GLHC scores for stage at presentation (P = .78). CONCLUSIONS: In a large sample of black and white individuals across diverse health care systems, higher scores on the GLHC predicted late disease stage at presentation. Although blacks had significantly higher GLHC scores, race was not associated with stage at presentation, nor was the association between GLHC and stage limited to blacks. Further work is needed to better understand this association and to develop interventions to better connect the religious and health care spheres. Cancer 2018;124:2578-87. © 2018 American Cancer Society.
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Neoplasias del Colon , Religión , Población Urbana , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Actitud Frente a la Salud/etnología , Negro o Afroamericano/psicología , Negro o Afroamericano/estadística & datos numéricos , Colon/patología , Neoplasias del Colon/diagnóstico , Neoplasias del Colon/patología , Estadificación de Neoplasias , Aceptación de la Atención de Salud/psicología , Aceptación de la Atención de Salud/estadística & datos numéricos , Factores Socioeconómicos , Estados Unidos , Población Urbana/estadística & datos numéricos , BlancoRESUMEN
OBJECTIVE: The application of adjunctive mediators in Autologous chondrocyte implantation (ACI) techniques might be useful for improving the dedifferentiated chondrocyte phenotype, to support neocartilage formation and inhibit post-traumatic cartilage destruction. In this study we examined if (a) interleukin 10 treatment can cause chondrogenic phenotype stabilization and matrix preservation in mechanically injured cartilage and if (b) IL-10 can promote chondrogenesis in a clinically applied collagen scaffold for ACI treatment. MATERIALS AND METHODS: For (a) bovine articular cartilage was harvested, subjected to an axial unconfined injury and treated with bovine IL-10 (1-10,000 pg/ng/ml). For (b) a post-operatively remaining ACI graft was treated with human IL-10. Expression levels of type I/II/X collagen, SOX9 and aggrecan were measured by qPCR (a,b). After 3 weeks cell death was analyzed (nuclear blebbing and TUNEL assay) and matrix composition was determined by GAG measurements and immunohistochemistry (aggrecan, type I/II collagen, hyaluronic acid). STATISTICS: One way ANOVA analysis with Bonferroni's correction. RESULTS: (a) IL-10 stabilized the chondrogenic phenotype after injurious compression and preserved matrix integrity. This was indicated by elevated expression of chondrogenic markers COL2A1, ACAN, SOX9, while COL1A1 and COL10A1 were reduced. An increased GAG content paralleled this and histological staining of type 2 collagen, aggrecan and toluidine blue were enhanced after 3 weeks. (b) IL-10 [100 pg/ml] improved the chondrogenic differentiation of human chondrocytes, which was accompanied by cartilaginous matrix formation after 3 weeks of incubation. CONCLUSION: Interleukin-10 is a versatile adjuvant candidate to control the post-injurious environment in cartilage defects and promote chondrogenesis in ACI grafts.
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Cartílago Articular/lesiones , Condrogénesis/efectos de los fármacos , Interleucina-10/farmacología , Animales , Apoptosis/efectos de los fármacos , Cartílago Articular/efectos de los fármacos , Cartílago Articular/metabolismo , Cartílago Articular/patología , Bovinos , Células Cultivadas , Condrocitos/efectos de los fármacos , Condrocitos/patología , Condrocitos/trasplante , Colágeno/metabolismo , Matriz Extracelular/metabolismo , Glicosaminoglicanos/metabolismo , Humanos , Andamios del TejidoRESUMEN
In Canada, 45% of new cancer cases and 63% of cancer deaths occur amongst Canadians 70 years and older. These older people with cancer and their families present particular needs and concerns that often remain under-recognized and unmet. As the number of older Canadians is expected to more than double in the next 25 years, we must integrate understanding of aging into oncology nursing practice, education, policy, and research, developing models of care that optimize appropriate outcomes for older adults. We present the Canadian Association of Nurses in Oncology (CANO) Oncology and Aging Special Interest Group (SIG), as an initiative to mobilize oncology nurses in addressing these concerns. In an overview of the 2015 CANO conference workshop that launched this group, we highlight practice concerns and priorities identified through interactive discussion with participants. We also describe development of the SIG since 2015, including objectives that will define next steps.
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Phosphatidylinositol analogs (PIAs) were originally designed to bind competitively to the Akt PH domain and prevent membrane translocation and activation. d-3-Deoxy-dioctanoylphosphatidylinositol (d-3-deoxy-diC8PI), but not compounds with altered inositol stereochemistry (e.g., l-3-deoxy-diC8PI and l-3,5-dideoxy-diC8PI), is cytotoxic. However, high resolution NMR field cycling relaxometry shows that both cytotoxic and non-toxic PIAs bind to the Akt1 PH domain at the site occupied by the cytotoxic alkylphospholipid perifosine. This suggests that another mechanism for cytotoxicity must account for the difference in efficacy of the synthetic short-chain PIAs. In MCF-7 breast cancer cells, with little constitutively active Akt, d-3-deoxy-diC8PI (but not l-compounds) decreases viability concomitant with increased cleavage of PARP and caspase 9, indicative of apoptosis. d-3-Deoxy-diC8PI also induces a decrease in endogenous levels of cyclins D1 and D3 and blocks downstream retinoblastoma protein phosphorylation. siRNA-mediated depletion of cyclin D1, but not cyclin D3, reduces MCF-7 cell proliferation. Thus, growth arrest and cytotoxicity induced by the soluble d-3-deoxy-diC8PI occur by a mechanism that involves downregulation of the D-type cyclin-pRb pathway independent of its interaction with Akt. This ability to downregulate D-type cyclins contributes, at least in part, to the anti-proliferative activity of d-3-deoxy-diC8PI and may be a common feature of other cytotoxic phospholipids.
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Neoplasias de la Mama/patología , Ciclina D1/metabolismo , Regulación hacia Abajo/efectos de los fármacos , Ácidos Fosfatidicos/farmacología , Fosfatidilinositoles/farmacología , Proteína de Retinoblastoma/metabolismo , Transducción de Señal/efectos de los fármacos , Muerte Celular/efectos de los fármacos , Femenino , Humanos , Células MCF-7 , Espectroscopía de Resonancia Magnética , Ácidos Fosfatidicos/química , Fosfatidilinositoles/química , Fosforilación/efectos de los fármacos , Dominios Homólogos a Pleckstrina , Proteínas Proto-Oncogénicas c-akt/química , Proteínas Proto-Oncogénicas c-akt/metabolismo , ARN Interferente Pequeño/metabolismo , Proteínas Quinasas p38 Activadas por Mitógenos/metabolismoAsunto(s)
Alfabetización en Salud , Neoplasias , Genómica , Humanos , Conocimiento , Neoplasias/terapiaRESUMEN
BACKGROUND: Cancer and its treatment lead to increased financial distress for patients. To the authors' knowledge, to date, no standardized patient-reported outcome measure has been validated to assess this distress. METHODS: Patients with AJCC Stage IV solid tumors receiving chemotherapy for at least 2 months were recruited. Financial toxicity was measured by the COmprehensive Score for financial Toxicity (COST) measure. The authors collected data regarding patient characteristics, clinical trial participation, health care use, willingness to discuss costs, psychological distress (Brief Profile of Mood States [POMS]), and health-related quality of life (HRQOL) as measured by the Functional Assessment of Cancer Therapy: General (FACT-G) and the European Organization for Research and Treatment of Cancer (EORTC) QOL questionnaires. Test-retest reliability, internal consistency, and validity of the COST measure were assessed using standard-scale construction techniques. Associations between the resulting factors and other variables were assessed using multivariable analyses. RESULTS: A total of 375 patients with advanced cancer were approached, 233 of whom (62.1%) agreed to participate. The COST measure demonstrated high internal consistency and test-retest reliability. Factor analyses revealed a coherent, single, latent variable (financial toxicity). COST values were found to be correlated with income (correlation coefficient [r] = 0.28; P<.001), psychosocial distress (r = -0.26; P<.001), and HRQOL, as measured by the FACT-G (r = 0.42; P<.001) and by the EORTC QOL instruments (r = 0.33; P<.001). Independent factors found to be associated with financial toxicity were race (P = .04), employment status (P<.001), income (P = .003), number of inpatient admissions (P = .01), and psychological distress (P = .003). Willingness to discuss costs was not found to be associated with the degree of financial distress (P = .49). CONCLUSIONS: The COST measure demonstrated reliability and validity in measuring financial toxicity. Its correlation with HRQOL indicates that financial toxicity is a clinically relevant patient-centered outcome. Cancer 2017;123:476-484. © 2016 American Cancer Society.
Asunto(s)
Quimioterapia/economía , Neoplasias/economía , Neoplasias/epidemiología , Adulto , Anciano , Ensayos Clínicos como Asunto , Análisis Costo-Beneficio , Femenino , Humanos , Masculino , Persona de Mediana Edad , Neoplasias/tratamiento farmacológico , Medición de Resultados Informados por el Paciente , Calidad de Vida , Encuestas y CuestionariosRESUMEN
PURPOSE: Adults with intellectual disabilities experience poorer physical health and health care quality, but there is limited information on the potential for reducing emergency hospital admissions in this population. We describe overall and preventable emergency admissions for adults with vs without intellectual disabilities in England and assess differences in primary care management before admission for 2 common ambulatory care-sensitive conditions (ACSCs). METHODS: We used electronic records to study a cohort of 16,666 adults with intellectual disabilities and 113,562 age-, sex-, and practice-matched adults without intellectual disabilities from 343 English family practices. Incident rate ratios (IRRs) from conditional Poisson regression were analyzed for all emergency and preventable emergency admissions. Primary care management of lower respiratory tract infections and urinary tract infections, as exemplar ACSCs, before admission were compared in unmatched analysis between adults with and without intellectual disabilities. RESULTS: The overall rate for emergency admissions for adults with vs without intellectual disabilities was 182 vs 68 per 1,000 per year (IRR = 2.82; 95% CI, 2.66-2.98). ACSCs accounted for 33.7% of emergency admissions among the former compared with 17.3% among the latter (IRR = 5.62; 95% CI, 5.14-6.13); adjusting for comorbidity, smoking, and deprivation did not fully explain the difference (IRR = 3.60; 95% CI, 3.25-3.99). Although adults with intellectual disability were at nearly 5 times higher risk for admission for lower respiratory tract infections and urinary tract infections, they had similar primary care use, investigation, and management before admission as the general population. CONCLUSIONS: Adults with intellectual disabilities are at high risk for preventable emergency admissions. Identifying strategies for better detecting and managing ACSCs, including lower respiratory and urinary tract infections, in primary care could reduce hospitalizations.
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Servicio de Urgencia en Hospital/estadística & datos numéricos , Discapacidad Intelectual , Uso Excesivo de los Servicios de Salud/estadística & datos numéricos , Admisión del Paciente/estadística & datos numéricos , Personas con Discapacidades Mentales/estadística & datos numéricos , Adulto , Estudios de Casos y Controles , Inglaterra/epidemiología , Femenino , Humanos , MasculinoRESUMEN
PURPOSE: Discussions between oncologists and advanced cancer patients (ACPs) may touch on the complex issue of clinical trial participation. Numerous initiatives have sought to improve the quality of these potentially difficult conversations. However, we have limited data about what ACPs know about clinical research as they enter such discussions as, to date, such research has focused on the period following informed consent. This study examines ACPs' understanding of clinical research in the treatment period before consent. METHODS: We conducted in-depth interviews with adult ACPs with limited treatment options at four clinics in an academic medical center. So as not to influence patients' perspectives, interviewers probed patients' knowledge of clinical research only if the patient first brought up the topic. Interviews (40-60 min) were audio-recorded, transcribed, and analyzed thematically and via quantitative content analysis by an interdisciplinary team. RESULTS: Of 78 patients recruited, 56 (72%) spontaneously brought up the topic of clinical research during interview and are included in this analysis. Qualitative thematic analysis and quantitative content analysis revealed that patients' knowledge varied in terms of (1) accuracy and (2) specificity (level of detail). ACPs who spoke with high specificity were not always accurate, and ACPs with accurate knowledge included both high- and low-specificity speakers. CONCLUSIONS: ACPs' knowledge of clinical research is variable. Patients who can discuss the technical details of their care may or may not understand the broader purpose and procedures of clinical trials. Understanding this variability is important for improving patient-provider communication about clinical research and supporting efforts to provide individualized care for ACPs.