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1.
J Appl Gerontol ; : 7334648241233375, 2024 Feb 12.
Artigo em Inglês | MEDLINE | ID: mdl-38347680

RESUMO

Comorbid dementia complicates cancer therapy decision-making in older adults. We aimed to synthesize the recent literature (<5 years) on the challenges associated with cancer therapy decision-making among older people living with dementia (PLWD) and their caregivers. Of the 20,763 references, 8767 had their title and abstract screened, and eight met the inclusion criteria. Six studies were qualitative, one study employed mixed methods, and one study was quasi-experimental. Most studies were conducted in the UK (89%) and reported homogeneity in race and geography. Breast (56%) and prostate (45%) were the most frequent reported cancers. Five studies (56%) reported multiple types of dementia, with two (22%) indicating stages. The studies indicated that communication between patients, caregivers, and clinical teams might alleviate stress caused by worsening health prospects and potential ethical concerns. Information from this review can lead to better-informed, patient-centered treatment decision processes among older PLWD and cancer, their caregivers, and clinicians.

2.
Support Care Cancer ; 32(2): 111, 2024 Jan 18.
Artigo em Inglês | MEDLINE | ID: mdl-38236449

RESUMO

BACKGROUND: National studies reporting the prevalence of cannabis use have focused on individuals with a history of cancer without distinction by their treatment status, which can impact symptom burden. While pain is a primary motivation to use cannabis in cancer, the magnitude of its association with cannabis use remains understudied. METHODS: We examined cannabis use and pain management among 5523 respondents of the Behavioral Risk Factor Surveillance System with a cancer history. Survey-weighted prevalence proportions of respondents' cannabis use are reported, stratified on cancer treatment status. Regression models estimated odds ratios (ORs) and 95% confidence intervals (CIs) of cancer-related pain and cannabis use. RESULTS: Cannabis use was slightly more prevalent in those undergoing active treatment relative to those who were not undergoing active treatment (9.3% vs. 6.2%; P=0.05). Those under active treatment were more likely to use cannabis medicinally (71.6% vs. 50.0%; P=0.03). Relative to those without cancer-related pain, persons with pain under medical control (OR 2.1, 95% CI, 1.4-3.2) or uncontrolled pain were twice as likely to use cannabis (OR 2.0, 95% CI, 1.1-3.5). CONCLUSIONS: Use of cannabis among cancer patients may be related to their treatment and is positively associated with cancer-related pain. Future research should investigate the associations of cannabis use, symptom burden, and treatment regimens across the treatment spectrum to facilitate interventions.


Assuntos
Dor do Câncer , Cannabis , Neoplasias , Humanos , Manejo da Dor , Dor do Câncer/tratamento farmacológico , Dor do Câncer/epidemiologia , Dor do Câncer/etiologia , Dor/tratamento farmacológico , Dor/epidemiologia , Dor/etiologia , Motivação , Neoplasias/complicações , Neoplasias/epidemiologia
4.
J Clin Pharmacol ; 64(1): 67-79, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37691236

RESUMO

Ritlecitinib is a small molecule in clinical development that covalently and irreversibly inhibits Janus kinase 3 (JAK3) and the TEC family of kinases (BTK, BMX, ITK, TXK, and TEC). This phase 1, open-label, parallel-group study assessed target occupancy and functional effects of ritlecitinib on JAK3 and TEC family kinases in healthy participants aged 18-60 years who received 50 or 200 mg single doses of ritlecitinib on day 1. Blood samples to assess ritlecitinib pharmacokinetics, target occupancy, and pharmacodynamics were collected over 48 hours. Target occupancy was assessed using mass spectroscopy. Functional inhibition of JAK3-dependent signaling was measured by the inhibition of the phosphorylation of its downstream target signal transducer and activator of transcription 5 (pSTAT5), following activation by interleukin 15 (IL-15). The functional inhibition of Bruton's tyrosine kinase (BTK)-dependent signaling was measured by the reduction in the upregulation of cluster of differentiation 69 (CD69), an early marker of B-cell activation, following treatment with anti-immunoglobulin D. Eight participants received one 50 mg ritlecitinib dose and 8 participants received one 200 mg dose. Ritlecitinib plasma exposure increased in an approximately dose-proportional manner from 50 to 200 mg. The maximal median JAK3 target occupancy was 72% for 50 mg and 64% for 200 mg. Ritlecitinib 50 mg had >94% maximal target occupancy of all TEC kinases, except BMX (87%), and 200 mg had >97% for all TEC kinases. For BTK and TEC, ritlecitinib maintained high target occupancy throughout a period of 48 hours. Ritlecitinib reduced pSTAT5 levels following IL-15- and BTK-dependent signaling in a dose-dependent manner. These target occupancy and functional assays demonstrate the dual inhibition of the JAK3- and BTK-dependent pathways by ritlecitinib. Further studies are needed to understand the contribution to clinical effects of inhibiting these pathways.


Assuntos
Interleucina-15 , Janus Quinase 3 , Humanos , Tirosina Quinase da Agamaglobulinemia , Transdução de Sinais , Inibidores de Proteínas Quinases/farmacologia , Fatores Imunológicos
5.
Cancer Res Commun ; 3(9): 1917-1926, 2023 09 22.
Artigo em Inglês | MEDLINE | ID: mdl-37772996

RESUMO

Symptoms such as pain, nausea, and anxiety are common in individuals with cancer. Treatment of these issues is often challenging. Cannabis products may be helpful in reducing the severity of these symptoms. While some studies include data on the prevalence of cannabis use among patients with cancer, detailed data remain limited, and none have reported the prevalence of cannabidiol (CBD) use in this population. Adult patients with cancer attending eight clinics at a large, NCI-designated Comprehensive Cancer Center completed a detailed, cannabis-focused questionnaire between 2021 and 2022. Eligible participants were diagnosed with invasive cancer and treated in the past 12 months. Summary statistics were calculated to describe the sample regarding cannabis use. Approximately 15% (n = 142) of consented patients (n = 934) reported current cannabis use (defined as use within the past 12 months). Among which, 75% reported cannabis use in the past week. Among current cannabis users, 39% (n = 56; 6% overall) used CBD products. Current users reported using cannabis a median of 4.5 (interquartile range: 0.6­7.0) days/week, 2.0 (1.0­3.0) times per use/day, and for 3 years (0.8­30.0). Use patterns varied by route of administration. Patients reported moderate to high relief of symptoms with cannabis use. This study is the most detailed to date in terms of cannabis measurement and provides information about the current state of cannabis use in active cancer. Future studies should include complete assessments of cannabis product use, multiple recruitment sites, and diverse patient populations. SIGNIFICANCE: Clinicians should be aware that patients are using cannabis products and perceive symptom relief with its use.


Assuntos
Canabidiol , Cannabis , Alucinógenos , Maconha Medicinal , Neoplasias , Adulto , Humanos , Cannabis/efeitos adversos , Canabidiol/uso terapêutico , Maconha Medicinal/uso terapêutico , Prevalência , Dor/induzido quimicamente , Agonistas de Receptores de Canabinoides , Neoplasias/tratamento farmacológico
6.
J Pharmacol Exp Ther ; 386(1): 80-92, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-37142443

RESUMO

Blocking chemokine receptor C-C chemoattractant cytokine (chemokine) receptor (CCR) 6-dependent T cell migration has therapeutic promise in inflammatory diseases. PF-07054894 is a novel CCR6 antagonist that blocked only CCR6, CCR7, and C-X-C chemoattractant cytokine (chemokine) receptor (CXCR) 2 in a ß-arrestin assay panel of 168 G protein-coupled receptors. Inhibition of CCR6-mediated human T cell chemotaxis by (R)-4-((2-(((1,4-Dimethyl-1H-pyrazol-3-yl)(1-methylcyclopentyl)methyl)amino)-3,4-dioxocyclobut-1-en-1-yl)amino)-3-hydroxy-N,N-dimethylpicolinamide (PF-07054894) was insurmountable by CCR6 ligand, C-C motif ligand (CCL) 20. In contrast, blockade of CCR7-dependent chemotaxis in human T cells and CXCR2-dependent chemotaxis in human neutrophils by PF-07054894 were surmountable by CCL19 and C-X-C motif ligand 1, respectively. [3H]-PF-07054894 showed a slower dissociation rate for CCR6 than for CCR7 and CXCR2 suggesting that differences in chemotaxis patterns of inhibition could be attributable to offset kinetics. Consistent with this notion, an analog of PF-07054894 with fast dissociation rate showed surmountable inhibition of CCL20/CCR6 chemotaxis. Furthermore, pre-equilibration of T cells with PF-07054894 increased its inhibitory potency in CCL20/CCR6 chemotaxis by 10-fold. The functional selectivity of PF-07054894 for inhibition of CCR6 relative to CCR7 and CXCR2 is estimated to be at least 50- and 150-fold, respectively. When administered orally to naïve cynomolgus monkeys, PF-07054894 increased the frequency of CCR6+ peripheral blood T cells, suggesting that blockade of CCR6 inhibited homeostatic migration of T cells from blood to tissues. PF-07054894 inhibited interleukin-23-induced mouse skin ear swelling to a similar extent as genetic ablation of CCR6. PF-07054894 caused an increase in cell surface CCR6 in mouse and monkey B cells, which was recapitulated in mouse splenocytes in vitro. In conclusion, PF-07054894 is a potent and functionally selective CCR6 antagonist that blocks CCR6-mediated chemotaxis in vitro and in vivo. SIGNIFICANCE STATEMENT: The chemokine receptor, C-C chemoattractant cytokine (chemokine) receptor 6 (CCR6) plays a key role in the migration of pathogenic lymphocytes and dendritic cells into sites of inflammation. (R)-4-((2-(((1,4-Dimethyl-1H-pyrazol-3-yl)(1-methylcyclopentyl)methyl)amino)-3,4-dioxocyclobut-1-en-1-yl)amino)-3-hydroxy-N,N-dimethylpicolinamide (PF-07054894) is a novel CCR6 small molecule antagonist that illustrates the importance of binding kinetics in achieving pharmacological potency and selectivity. Orally administered PF-07054894 blocks homeostatic and pathogenic functions of CCR6, suggesting that it is a promising therapeutic agent for the treatment of a variety of autoimmune and inflammatory diseases.


Assuntos
Quimiocinas CC , Interleucina-23 , Humanos , Animais , Camundongos , Quimiocinas CC/genética , Receptores CCR7 , Ligantes , Linfócitos T , Inflamação , Receptores CCR6
7.
JCO Oncol Pract ; 19(6): 327-329, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-37075269

RESUMO

Delirium continues to be challenging for medical providers, patients, and caregivers. In a recent editorial, the authors review a retrospective analysis of critically ill, nonterminal patients with cancer admitted to a mixed medical-surgical ICU and discuss how these findings offer opportunities for intervention and goals-of-care conversations.


Assuntos
Delírio , Neoplasias , Humanos , Prognóstico , Estudos Retrospectivos , Delírio/diagnóstico , Unidades de Terapia Intensiva
8.
Artigo em Inglês | MEDLINE | ID: mdl-36990682

RESUMO

BACKGROUND: The total artificial heart (TAH) is an implanted device approved as a modality to stabilize patients with severe biventricular heart failure or persistent ventricular arrhythmias for evaluation and bridge to transplantation. According to the Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS), about 450 patients received a TAH between 2006 and 2018. Patients being evaluated for a TAH are often critically ill and a TAH offers the best chance at survival. Given the prognostic uncertainty of these patients, there is a crucial need for preparedness planning to help patients and their caregivers plan for living and supporting a loved one with a TAH. AIM: To describe an approach to preparedness planning and highlight the importance of palliative care. METHODS: We reviewed the current needs and approaches to preparedness planning for a TAH. We categorized our findings and suggest a guide to maximize conversations with patients and their decision makers. RESULTS: We identified four critical areas to address: the decision maker, minimal acceptable outcome/maximal acceptable burden, living with the device, and dying with the device. We suggest using a framework of mental and physical outcomes and locations of care as a way to identify minimal acceptable outcome and maximal acceptable burden. CONCLUSION: Decision making for a TAH is complex. There is an urgency and patients do not always have capacity. Identifying legal decision makers and social support is critical. The surrogate decision makers should be included in preparedness planning including discussions about end-of-life care and treatment discontinuation. Having palliative care as members of the interdisciplinary mechanical circulatory support team can assist in these preparedness conversations.

9.
Appl Ergon ; 110: 104000, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-36958252

RESUMO

'Medication errors' are a significant concern and are associated with a higher incidence of adverse events and unintentional patient harm than any other aspect of healthcare. While much research has focused on adverse medication errors, limited studies have specifically examined 'normal' medication delivery performance and the interactions between tasks, agents, and information within the medication administration system. This article describes a study that applied the Event Analysis of Systemic Teamwork (EAST) model to study the hospital medication administration system to identify opportunities to optimise performance and patient safety. Key findings of this study demonstrate that this is a highly complex system, comprising many social agents and a relatively closely linked series of tasks and information. However, most of the workload relies on a small proportion of healthcare professionals. Significantly, the patient has a minimal role in the medication administration system during their hospital stay. The research has shown that this approach enables mapping networks and their interdependencies to optimise the system as a whole rather than its parts in isolation.


Assuntos
Erros de Medicação , Segurança do Paciente , Humanos , Erros de Medicação/prevenção & controle , Pessoal de Saúde , Instalações de Saúde , Análise de Sistemas
11.
J Cancer Educ ; 38(1): 301-308, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-34767182

RESUMO

The current study evaluated formal training around spiritual care for healthcare providers and the relationships between that training, perceived barriers to spiritual care, and frequency of inquiry around spiritual topics. A mixed methods explanatory sequential design was used. Quantitative methods included an online survey administered to providers at The Ohio State University Comprehensive Cancer Center. Main and interactive effects of formal training and barriers to spiritual care on frequency of inquiry around spiritual topics were assessed with two-way ANOVA. Qualitative follow-up explored provider strategies to engage spiritual topics. Among 340 quantitative participants, most were female (82.1%) or White (82.6%) with over one-half identifying as religious (57.5%). The majority were nurses (64.7%) and less than 10% of all providers (n = 26) indicated formal training around spiritual care. There were main effects on frequency of inquiry around spiritual topics for providers who indicated "personal discomfort" as a barrier (p < 0.001), but not formal training (p = 0.526). Providers who indicated "personal discomfort" as a barrier inquired about spirituality less frequently, regardless of receiving formal training (M = 8.0, SD = 1.41) or not (M = 8.76, SD = 2.96). There were no interactive effects between training and "may offend patients" or "personal discomfort" (p = 0.258 and 0.125, respectively). Qualitative analysis revealed four strategies with direct and indirect approaches: (1) permission-giving, (2) self-awareness/use-of-self, (3) formal assessment, and (4) informal assessment. Training for providers should emphasize self-awareness to address intrapersonal barriers to improve the frequency and quality of spiritual care for cancer patients.


Assuntos
Terapias Espirituais , Espiritualidade , Humanos , Feminino , Masculino , Pessoal de Saúde/educação , Inquéritos e Questionários , Ohio
12.
Bioanalysis ; 14(10): 627-692, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35578974

RESUMO

The 15th edition of the Workshop on Recent Issues in Bioanalysis (15th WRIB) was held on 27 September to 1 October 2021. Even with a last-minute move from in-person to virtual, an overwhelmingly high number of nearly 900 professionals representing pharma and biotech companies, contract research organizations (CROs), and multiple regulatory agencies still eagerly convened to actively discuss the most current topics of interest in bioanalysis. The 15th WRIB included three Main Workshops and seven Specialized Workshops that together spanned 1 week in order to allow exhaustive and thorough coverage of all major issues in bioanalysis, biomarkers, immunogenicity, gene therapy, cell therapy and vaccines. Moreover, in-depth workshops on biomarker assay development and validation (BAV) (focused on clarifying the confusion created by the increased use of the term "context of use" [COU]); mass spectrometry of proteins (therapeutic, biomarker and transgene); state-of-the-art cytometry innovation and validation; and critical reagent and positive control generation were the special features of the 15th edition. This 2021 White Paper encompasses recommendations emerging from the extensive discussions held during the workshop, and is aimed to provide the bioanalytical community with key information and practical solutions on topics and issues addressed, in an effort to enable advances in scientific excellence, improved quality and better regulatory compliance. Due to its length, the 2021 edition of this comprehensive White Paper has been divided into three parts for editorial reasons. This publication (Part 2) covers the recommendations on ISR for Biomarkers, Liquid Biopsies, Spectral Cytometry, Inhalation/Oral & Multispecific Biotherapeutics, Accuracy/LLOQ for Flow Cytometry. Part 1A (Endogenous Compounds, Small Molecules, Complex Methods, Regulated Mass Spec of Large Molecules, Small Molecule, PoC), Part 1B (Regulatory Agencies' Inputs on Bioanalysis, Biomarkers, Immunogenicity, Gene & Cell Therapy and Vaccine) and Part 3 (TAb/NAb, Viral Vector CDx, Shedding Assays; CRISPR/Cas9 & CAR-T Immunogenicity; PCR & Vaccine Assay Performance; ADA Assay Comparability & Cut Point Appropriateness) are published in volume 14 of Bioanalysis, issues 9 and 11 (2022), respectively.


Assuntos
Citometria de Fluxo , Biomarcadores/análise , Citometria de Fluxo/métodos , Humanos , Indicadores e Reagentes , Biópsia Líquida , Espectrometria de Massas
13.
Front Oncol ; 12: 789910, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35463315

RESUMO

Objective: Women make up a majority of the gynecologic oncology workforce. Increasing the numbers of women in leadership has been proposed as a path towards professional gender equity. This study examined whether leadership gender and departmental infrastructure impact the work environment for women gynecologic oncologists. Methods: Members of a 472-member private Facebook group "Women of Gynecologic Oncology" (WGO) who self-identified as women gynecologic oncologists provided demographics, practice infrastructure, personal experience with workplace bullying, gender discrimination, microaggressions using a REDcap survey platform. Results: Of 250 (53%) respondents to this survey, most were younger than age 50 years (93.6%); White (82.2%) and non-Hispanic (94.3%); married (84.7%); and parenting (75.2%). Practice environments included academic (n=152, 61.0%), hospital employed (n=57, 22.9%), and private practice (n=31, 12.4%), and 89.9% supervised trainees. A significant percent of respondents had experienced bullying (52.8%), gender discrimination (57%) and microaggressions (83%). Age, race, ethnicity, practice setting, or mentorship were not statistically significantly associated with these experiences. Reported perpetrators were varied and included colleagues (84%), patients (44%), staff (41%), administrators (18%), and trainees (16%). Prevalence of bullying (55.0 vs 47.7%, p=0.33), gender discrimination (59.1 vs 52.3%, p=0.33) and microaggressions (83.3 vs 83.0%, p=1.00) were similar irrespective of departmental leadership gender. Conclusions: Women gynecologic oncologists report a high prevalence of workplace bullying, gender discrimination and microaggressions regardless of the gender of their immediate leadership. Proactive and deliberate structural interventions to improve the work environment for surgeons who are women are urgently needed.

14.
Curr Hematol Malig Rep ; 17(1): 31-38, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-35028826

RESUMO

Hematologic malignancies are most likely to present in the seventh and eighth decades of life. Continued population growth will lead to increasing numbers of older adults with hematologic malignancies. Oncology care for older adults is complex and must account for the effect of aging on disease biology and treatment tolerance. Multidisciplinary oncology care has been utilized in solid tumor oncology for decades, initially driven by the need for multi-modality treatment. In this review, we make the case for multidisciplinary oncogeriatric care for older adults with hematologic malignancies in order to best navigate the intersection of aging and blood cancer.


Assuntos
Neoplasias Hematológicas , Neoplasias , Idoso , Envelhecimento , Neoplasias Hematológicas/diagnóstico , Neoplasias Hematológicas/epidemiologia , Neoplasias Hematológicas/terapia , Humanos , Oncologia
15.
J Geriatr Oncol ; 13(4): 410-415, 2022 05.
Artigo em Inglês | MEDLINE | ID: mdl-35074322

RESUMO

BACKGROUND: Older adults with gastrointestinal cancers undergoing surgery often experience poor outcomes, such as prolonged postoperative hospital length of stay (LOS), intensive care unit (ICU) use, hospital readmissions, and complications. Involvement of geriatricians in the care of older adults with cancer can improve outcomes. We conducted a randomized trial of a perioperative geriatric intervention (PERI-OP) in older patients with gastrointestinal cancer undergoing surgery. METHODS: From 9/2016-4/2019, we randomly assigned patients age ≥ 65 with gastrointestinal cancer planning to undergo surgical resection to receive PERI-OP or usual care. Patients assigned to PERI-OP met with a geriatrician preoperatively in the outpatient setting and postoperatively as an inpatient consultant. The primary outcome was postoperative hospital LOS. Secondary outcomes included postoperative ICU use, 90-day hospital readmission rates, and complication rates. We conducted intention-to-treat (ITT) and per-protocol (PP) analyses. RESULTS: ITT analyses included 137/160 patients who underwent surgery (usual care = 68/78, intervention = 69/82). PP analyses included the 68 usual care patients and the 30/69 intervention patients who received the preoperative and postoperative intervention components. ITT analyses demonstrated no significant differences between intervention and usual care in postoperative hospital LOS (7.23 vs 8.21 days, P = 0.374), ICU use (23.2% vs 32.4%, P = 0.257), 90-day hospital readmission rates (21.7% vs 25.0%, P = 0.690), or complication rates (17.4% vs 20.6%, P = 0.668). In PP analyses, intervention patients had shorter postoperative hospital LOS (5.90 vs 8.21 days, P = 0.024), but differences in ICU use (13.3% vs 32.4%, P = 0.081), 90-day hospital readmission rates (16.7% vs 25.0%, P = 0.439), and complication rates (6.7% vs 20.6%, P = 0.137) remained non-significant. CONCLUSIONS: In this randomized trial, PERI-OP did not have a significant impact on postoperative hospital LOS, ICU use, hospital readmissions, or complications. However, the subgroup who received PERI-OP as planned experienced encouraging results. Future studies of PERI-OP should include efforts, such as telehealth, to ensure the intervention is delivered as planned.


Assuntos
Neoplasias , Readmissão do Paciente , Idoso , Humanos , Tempo de Internação , Neoplasias/complicações , Neoplasias/cirurgia , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia
16.
Am J Hosp Palliat Care ; 39(9): 1046-1051, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34607493

RESUMO

BACKGROUND: There is increased interest in the role of spirituality in the cancer care context, but how it may inspire individuals to pursue a career as a healthcare provider is unknown. We sought to determine the relationship between intrinsic religiosity, religious identity, provider role, and spiritual motivations to practice medicine. METHODS: A cross-sectional survey was administered to healthcare providers at a large, Midwest Comprehensive Cancer Center. The relationship between provider type, intrinsic religiosity, religious identity, and spiritual motivations to practice medicine was assessed with binary logistic regression. RESULTS: Among 340 participants, most were female (82.1%) or Caucasian (82.6%) and identified as being religious (57.5%); median age was 35 years (IQR: 31-48). Providers included nurses (64.7%), physicians (17.9%), and "other" (17.4%). Compared with physicians, nurses were less likely to agree that they felt responsible for reducing pain and suffering in the world (OR: 0.12, p = 0.03). Similarly, "other" providers were less likely than physicians to believe that the practice of medicine was a calling (OR: 0.28, p = 0.02). Providers with a high self-reported intrinsic religiosity demonstrated a much greater likelihood to believe that the practice of medicine is a calling (OR:1.75, p = 0.001), as well as believe that personal R&S beliefs influence the practice of medicine (OR:3.57, p < 0.001). Provider religious identity was not associated with spiritual motivations to practice medicine (all p > 0.05). CONCLUSION: Intrinsic religiosity had the strongest relationship with spiritual motivations to practice medicine. Understanding these motivations may inform interventions to avoid symptoms of provider burnout in cancer care.


Assuntos
Medicina , Neoplasias , Adulto , Estudos Transversais , Feminino , Humanos , Masculino , Motivação , Neoplasias/terapia , Religião , Religião e Medicina , Espiritualidade , Inquéritos e Questionários
17.
Cancer Gene Ther ; 29(3-4): 369-382, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-33753870

RESUMO

Vigil® is a personalized vaccine that enhances tumor neoantigen expression. We investigated for the first time safety and efficacy of Vigil in combination with atezolizumab in relapsed ovarian cancer (OC) patients. This is a randomized, Phase 1 study of Vigil, an autologous tumor tissue transfected vaccine encoding for GMCSF and bi-shRNA-furin thereby creating enhanced immune activation and TGFß expression control. Part 1 is a safety assessment of Vigil (1 × 10e7 cells/mL/21 days) plus atezolizumab (1200 mg/21 days). Part 2 is a randomized study of Vigil first (Vigil-1st) or atezolizumab first (Atezo-1st) for two cycles followed by the combination of both agents. The primary endpoint of the study was the determination of safety. Twenty-four patients were enrolled in the study; three patients to Part 1 and 21 to Part 2. Patients in Part 1 completed combination therapy without dose-limiting toxicity justifying expansion to Part 2. Twenty-one patients were randomized (1:1) to Part 2 to Vigil-1st (n = 11) or Atezo-1st (n = 10). Grade 3/4 treatment-related adverse events of Atezo-1st vs. Vigil-1st were 17.2% vs. 5.1%. Median overall survival (OS) was not reached (NR) (Vigil-1st) vs. 10.8 months (Atezo-1st) (hazard ratio [HR] 0.33). The exploratory subset analysis of BRCAwt suggested improved OS benefit [NR in Vigil-1st vs. 5.2 months in Atezo-1st, HR 0.16, p 0.027]. The Vigil-1st combination therapy with atezolizumab was safe and results in support continued investigation in BRCAwt patients.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica , Neoplasias Ovarianas , Anticorpos Monoclonais Humanizados , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma Epitelial do Ovário , Feminino , Humanos , Modafinila/uso terapêutico , Recidiva Local de Neoplasia , Neoplasias Ovarianas/tratamento farmacológico
18.
Front Oncol ; 11: 775050, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34956894

RESUMO

The incidence of hematologic malignancies (HMs) is highest in the seventh decade of life and coincides with increasing occult, age-related vulnerabilities. Identification of frailty is useful in prognostication and treatment decision-making for older adults with HMs. This real-world analysis describes 311 older adults with HMs evaluated in a multidisciplinary oncogeriatric clinic. The accumulation of geriatric conditions [1-unit increase, hazards ratio (HR) = 1.13, 95% CI 1.00-1.27, p = 0.04] and frailty assessed by the Rockwood Clinical Frailty Scale (CFS, mild/moderate/severe frailty vs. very fit/well, HR = 2.59, 95% CI 1.41-4.78, p = 0.002) were predictive of worse overall survival. In multivariate analysis, HM type [acute leukemia, HR = 3.84, 95% CI 1.60-9.22, p = 0.003; myelodysplastic syndrome (MDS)/myeloproliferative neoplasm (MPN)/bone marrow failure, HR = 2.65, 95% CI 1.10-6.35, p = 0.03], age (per 5-year increase, HR = 1.46, 95% CI 1.21-1.76, p < 0.001), hemoglobin (per 1 g/dl decrease, HR = 1.21, 95% CI 1.05-1.40, p = 0.009), deficit in activities of daily living (HR = 2.20, 95% CI 1.11-4.34, p = 0.02), and Mini Nutrition Assessment score (at-risk of malnutrition vs. normal, HR = 2.00, 95% CI 1.07-3.73, p = 0.03) were independently associated with risk of death. The most commonly prescribed geriatric interventions were in the domains of audiology (56%) and pharmacy (54%). The Rockwood CFS correlated with prescribed interventions in nutrition (p = 0.01) and physical function (p < 0.001) domains. Geriatric assessment with geriatric intervention can be practically integrated into the routine care of older adults with HMs.

19.
Geriatr Orthop Surg Rehabil ; 12: 21514593211003065, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33868766

RESUMO

INTRODUCTION: Persistent misconceptions of frailty and dementia in geriatric patients impact physician-patient communication and leave patients vulnerable to disempowerment. Physicians may inappropriately focus the discussion of treatment options to health care proxies instead of patients. Our study explores the consenting process in a decision-making capable orthogeriatric trauma patient population to determine if there is a relationship between increased patient age and surgical consent by health care proxy. METHODS: Patients aged 65 and older who underwent operative orthopaedic fracture fixation between 1 of 2 Level 1 Trauma Centers were retrospectively reviewed. Decision-making capable status was defined as an absence of patient history of cognitive impairment and a negative patient pre-surgical Confusion Assessment Method (CAM) and Mini-Cog Assessment screen. Provider of surgical consent was the main outcome and was determined by signature on the consent form. RESULTS: 510 patients were included, and 276 (54.1%) patients were deemed capable of consent. In 27 (9.8%) of 276 decision-capable patients, physicians obtained consent from health care proxies. 20 of these 27 patients (74.1%) were 80 years of age or older. However, in patients aged 70 to 79, only 7 health care proxies provided consent. (p = 0.07). For every unit increase in age, the log odds of proxy consent increased by .0008 (p < 0.001). Age (p < 0.001), income level (p = 0.03), and physical presence of proxy at consult (p < 0.001) were factors associated with significantly increased utilization of health care proxy provided consent. Language other than English was a significant predictor of proxy-provided consent (p = 0.035). 48 (22%) decision-making incapable patients provided their own surgical consent. DISCUSSION: The positive linear association between age and health care proxy provided consent in cognitively intact geriatric orthopaedic patients indicates that increased patient age impacts the consenting process. Increased physician vigilance and adoption of institutional consenting guidelines can reinforce appropriate respect of geriatric patients' consenting capacity.

20.
Ergonomics ; 64(8): 1072-1090, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-33775234

RESUMO

Communication failure within health care teams is a major cause of patient harm across health care settings. Factors which contribute to communication failure include actual or perceived 'power'. Whilst a great deal of ergonomics research has focussed on teamwork in health care, the role of power in relation to measurable patient safety and performance outcomes remains relatively unknown. This article presents the findings from a review of the literature on power within multidisciplinary health care team settings. Following a systematic literature search, nineteen studies were evaluated in terms of research design, methods and analyses across the included studies. The main impacts resulting from power imbalances include negative effects on team collaboration, decision-making, communication and overall performance. Wider patient safety research, and more specifically the ergonomics discipline, is encouraged to address the complex interplay between power and teamwork in the health care sector.Practitioner Statement: We conducted a review of studies focussed on the influence of power on teamwork in health care. The findings show that power can have negative impacts on collaboration, decision-making, communication, and team performance. We conclude that power represents an important area for ergonomics, both in health care and other settings.Abbreviations: CRM: crew resource management; TEM: threat and error management; SNA: social network analysis; EAST: event analysis of systemic teamwork.


Assuntos
Atenção à Saúde , Equipe de Assistência ao Paciente , Comunicação , Humanos , Segurança do Paciente
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