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1.
Nanotechnology ; 35(28)2024 Apr 24.
Artigo em Inglês | MEDLINE | ID: mdl-38522104

RESUMO

Surface enhanced Raman spectroscopy (SERS) is a powerful analytical technique that has found application in the trace detection of a wide range of contaminants. In this paper, we report on the fabrication of 2D silver nanodendrites, on silicon chips, synthesized by electrochemical reduction of AgNO3at microelectrodes. The formation of nanodendrites is tentatively explained in terms of electromigration and diffusion of silver ions. Electrochemical characterization suggests that the nanodendrites do not stay electrically connected to the microelectrode. The substrates show SERS activity with an enhancement factor on the order of 106. Density functional theory simulations were carried out to investigate the suitability of the fabricated substrate for pesticide monitoring. These substrates can be functionalized with cyclodextrin macro molecules to help with the detection of molecules with low affinity with silver surfaces. A proof of concept is demonstrated with the detection of the herbicide 2-methyl-4-chlorophenoxyacetic acid (MCPA).

2.
J Relig Health ; 61(5): 3589-3614, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-35064445

RESUMO

Mental health clinicians frequently study the religion and spirituality (R/S) of their patients. There is, however, a paucity of empirical research concerning R/S of patients with bipolar disorder. This lack is exacerbated by the absence of an evaluation of how these studies relate to each other. Reviews to date concern almost exclusively quantitative studies; a review that synthesizes quantitative and qualitative research is needed. The aim of this paper is to provide a synthesis of empirical studies that is useful in clinical practice. Systematic searches for relevant journal articles in SCOPUS, PubMed, and PsycInfo found 14 quantitative and four qualitative studies. The research reveals that intrinsic religiosity and positive religious coping are the dimensions of R/S that have the most positive correlations with improvement of bipolar disorder symptoms as revealed by measures of clinical outcomes. Patients struggle with their religious experiences, and they wish that R/S would be taken into account by mental health professionals. The quantitative studies are not in conflict with the patient/person-centered focus of qualitative studies. This integration of quantitative data with a patient/person-centered focus shows how belief and illness affect each other. The tensions inherent in such an integration provide new insights for research and treatment. Unfortunately, the qualitative literature has not caught up with quantitative approaches in terms of diagnostic rigor.


Assuntos
Transtorno Bipolar , Espiritualidade , Adaptação Psicológica , Transtorno Bipolar/psicologia , Humanos , Saúde Mental , Religião
3.
Sensors (Basel) ; 21(10)2021 May 19.
Artigo em Inglês | MEDLINE | ID: mdl-34069670

RESUMO

Water is a precious resource that is under threat from a number of pressures, including, for example, release of toxic compounds, that can have damaging effect on ecology and human health. The current methods of water quality monitoring are based on sample collection and analysis at dedicated laboratories. Recently, electrochemical-based methods have attracted a lot of attention for environmental sensing owing to their versatility, sensitivity and their ease of integration with cost effective, smart and portable readout systems. In the present work, we report on the fabrication and characterization of platinum-based interdigitated microband electrodes arrays, and their application for trace detection of copper. Using square wave voltammetry after acidification with mineral acids, a limit of detection of 0.8 µg/L was achieved. Copper detection was also undertaken on river water samples and compared with standard analytical techniques. The possibility of controlling the pH at the surface of the sensors-thereby avoiding the necessity to add mineral acids-was investigated. By applying potentials to drive the water splitting reaction at one comb of the sensor's electrode (the protonator), it was possible to lower the pH in the vicinity of the sensing electrode. Detection of standard copper solutions down to 5 µg/L (ppb) using this technique is reported. This reagent free method of detection opens the way for autonomous, in situ monitoring of pollutants in water bodies.

4.
Int J Nurs Pract ; 26(1): e12798, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31749210

RESUMO

AIM: The Suicide Crisis Assessment Nurse service has been developed as a Primary Care suicide intervention over the last decade. The current study aimed to describe the demographic details of users of this nurse led service, and to evaluate subsequent care pathways following this intervention. METHODS: This study was conducted using a retrospective file review with a cross-sectional observational design investigating demographic details of service users and care pathways in a Suicide Crisis Assessment Nurse service within a defined catchment area of Ireland between June 2015 and May 2017. RESULTS: The majority of referrals were managed in Primary Care following Suicide Crisis Assessment Nurse intervention. There was an increase in Primary Care management pathway in the second year of the service which was independent of age and gender. CONCLUSION: There was an increase in referrals to the service over time, and the majority of presentations were managed in primary care following Suicide Crisis Assessment Nurse intervention. The study suggests that primary care interventions for suicidal crises merit further research.


Assuntos
Intervenção em Crise , Procedimentos Clínicos , Atenção Primária à Saúde , Encaminhamento e Consulta , Prevenção do Suicídio , Adulto , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Papel do Profissional de Enfermagem , Estudos Retrospectivos
6.
Future Oncol ; 12(15): 1759-68, 2016 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-27093976

RESUMO

UNLABELLED: We describe the rationale and design of the ongoing randomized, active-controlled, multicenter, Phase III study evaluating the efficacy of pixantrone and rituximab versus gemcitabine and rituximab in patients with diffuse large B-cell lymphoma or follicular grade 3 lymphoma, who are ineligible for high-dose chemotherapy and stem cell transplantation, and who failed front-line regimens containing rituximab. The administration schedule is pixantrone 50 mg/m(2) intravenously (iv.) or gemcitabine 1000 mg/m(2) iv. on days 1, 8 and 15, combined with rituximab 375 mg/m(2) iv. on day 1, up to six cycles. Pixantrone has a conditional European marketing approval for monotherapy in adults with multiple relapsed or refractory aggressive B-cell non-Hodgkin lymphoma. Our trial explores the efficacy of combining pixantrone with rituximab and completes postauthorization measures. TRIAL REGISTRATION NUMBER: NCT01321541.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Linfoma não Hodgkin/tratamento farmacológico , Recidiva Local de Neoplasia/tratamento farmacológico , Adulto , Idoso , Desoxicitidina/administração & dosagem , Desoxicitidina/efeitos adversos , Desoxicitidina/análogos & derivados , Feminino , Humanos , Isoquinolinas/administração & dosagem , Isoquinolinas/efeitos adversos , Masculino , Pessoa de Meia-Idade , Projetos de Pesquisa , Rituximab/administração & dosagem , Rituximab/efeitos adversos , Gencitabina
7.
PLoS One ; 19(3): e0298977, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38437233

RESUMO

OBJECTIVE: To analyse the relationship between health app quality with user ratings and the number of downloads of corresponding health apps. MATERIALS AND METHODS: Utilising a dataset of 881 Android-based health apps, assessed via the 300-point objective Organisation for the Review of Care and Health Applications (ORCHA) assessment tool, we explored whether subjective user-level indicators of quality (user ratings and downloads) correlate with objective quality scores in the domains of user experience, data privacy and professional/clinical assurance. For this purpose, we applied spearman correlation and multiple linear regression models. RESULTS: For user experience, professional/clinical assurance and data privacy scores, all models had very low adjusted R squared values (< .02). Suggesting that there is no meaningful link between subjective user ratings or the number of health app downloads and objective quality measures. Spearman correlations suggested that prior downloads only had a very weak positive correlation with user experience scores (Spearman = .084, p = .012) and data privacy scores (Spearman = .088, p = .009). There was a very weak negative correlation between downloads and professional/clinical assurance score (Spearman = -.081, p = .016). Additionally, user ratings demonstrated a very weak correlation with no statistically significant correlations observed between user ratings and the scores (all p > 0.05). For ORCHA scores multiple linear regression had adjusted R-squared = -.002. CONCLUSION: This study highlights that widely available proxies which users may perceive to signify the quality of health apps, namely user ratings and downloads, are inaccurate predictors for estimating quality. This indicates the need for wider use of quality assurance methodologies which can accurately determine the quality, safety, and compliance of health apps. Findings suggest more should be done to enable users to recognise high-quality health apps, including digital health literacy training and the provision of nationally endorsed "libraries".


Assuntos
Letramento em Saúde , Bibliotecas , Aplicativos Móveis , Saúde Digital , Modelos Lineares
8.
JMIR Hum Factors ; 2024 Sep 23.
Artigo em Inglês | MEDLINE | ID: mdl-39446017

RESUMO

BACKGROUND: Remote patient monitoring (RPM) aims to improve patient access to care and communication with clinical providers. Overall, understanding the usability of RPM applications and their influence on clinical care workflows is limited from the perspectives of clinician end users at a cancer center in the Northeast, United States. OBJECTIVE: Explore the usability and functionality of RPM and elicit the perceptions and experiences of oncology clinicians using RPM for oncology patients after hospital discharge. METHODS: The sample included 30 of 98 clinicians (31% response rate) managing at least five patients in the RPM program and responding to the m-Health Usability between March 2021- October 2021. Overall, clinicians responded positively to the survey. Item responses with the highest proportion of disagreement were explored further. A nested sample of five clinicians who responded to the study survey (30% response rate) participated in interview sessions conducted from November 2021 to February 2022, and averaged 60 minutes each. RESULTS: Survey responses highlighted that RPM was easy to use and learn and verified symptom alerts during follow-up phone calls. Areas to improve identified practice changes from reporting RPM alerts through digital portals and its influence on clinicians' workload burden. Interview sessions revealed three main themes: clinician understanding and usability constraints, patient constraints, and suggestions for improving the program. Subthemes for each theme were explored, characterizing technical and functional limitations that could be addressed to enhance efficiency, workflow, and user experience. CONCLUSIONS: Clinicians support the value of RPM for improving symptom management and engaging with providers. Functional changes to enhance the program's utility, such as input from patients about temporal changes in their symptoms and technical resources for home monitoring devices.

9.
Front Oncol ; 14: 1420888, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39429470

RESUMO

Pretreatment prognostication, on-treatment monitoring, and early detection of physiological symptoms are considerable challenges in cancer. We describe the feasibility of high-resolution wearable data (steps per day, walking speed) to longitudinally profile physiological trajectories extracted from Apple Health data in three patients with lung cancer from diagnosis through cancer treatment after obtaining informed consent. We used descriptive statistics to describe our approach of building longitudinal physiological profiles. The wearable data monitoring period ranged from 58 to 135 weeks, with between 34,319 and 103,535 distinct digital physiological measures collected during this period-the equivalent to 41 measures per day/patient. Longitudinal profiling revealed that wearable data accurately captured physiological changes linked with clinical events such as surgery and hospitalizations as well as initiation (and cessation) of systemic cancer treatment in all three patients. These findings suggest that wearable devices could play a critical role in the management of lung cancer, although larger studies are needed to confirm these preliminary observations and validate their generalizability. Wearable devices hold significant promise for the development of personalized "digital biomarkers," which may enhance risk stratification and management in oncology.

10.
J Natl Cancer Inst Monogr ; 2024(64): 92-99, 2024 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-38924790

RESUMO

The COVID-19 pandemic placed a spotlight on the potential to dramatically increase the use of telehealth across the cancer care continuum, but whether and how telehealth can be implemented in practice in ways that reduce, rather than exacerbate, inequities are largely unknown. To help fill this critical gap in research and practice, we developed the Framework for Integrating Telehealth Equitably (FITE), a process and evaluation model designed to help guide equitable integration of telehealth into practice. In this manuscript, we present FITE and showcase how investigators across the National Cancer Institute's Telehealth Research Centers of Excellence are applying the framework in different ways to advance digital and health equity. By highlighting multilevel determinants of digital equity that span further than access alone, FITE highlights the complex and differential ways structural determinants restrict or enable digital equity at the individual and community level. As such, achieving digital equity will require strategies designed to not only support individual behavior but also change the broader context to ensure all patients and communities have the choice, opportunity, and resources to use telehealth across the cancer care continuum.


Assuntos
COVID-19 , Continuidade da Assistência ao Paciente , Neoplasias , Telemedicina , Humanos , Neoplasias/terapia , Neoplasias/epidemiologia , COVID-19/epidemiologia , Continuidade da Assistência ao Paciente/organização & administração , Estados Unidos , SARS-CoV-2 , Equidade em Saúde , Disparidades em Assistência à Saúde , Acessibilidade aos Serviços de Saúde , Pandemias
11.
J Natl Cancer Inst Monogr ; 2024(64): 76-82, 2024 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-38924792

RESUMO

Modern cancer care is costly and logistically burdensome for patients and their families despite an expansion of technology and medical advances that create the opportunity for novel approaches to care. Therefore, there is a growing appreciation for the need to leverage these innovations to make cancer care more patient centered and convenient. The Memorial Sloan Kettering Making Telehealth Delivery of Cancer Care at Home Efficient and Safe Telehealth Research Center is a National Cancer Institute-designated and funded Telehealth Research Center of Excellence poised to generate the evidence necessary to inform the appropriate use of telehealth as a strategy to improve access to cancer services that are convenient for patients. The center will evaluate telehealth as a strategy to personalize cancer care delivery to ensure that it is not only safe and effective but also convenient and efficient. In this article, we outline this new center's research strategy, as well as highlight challenges that exist in further integrating telehealth into standard oncology practice based on early experiences.


Assuntos
Neoplasias , Assistência Centrada no Paciente , Telemedicina , Humanos , Neoplasias/terapia , Estados Unidos , Oncologia/métodos , Acessibilidade aos Serviços de Saúde , National Cancer Institute (U.S.)
12.
Mycologia ; 105(1): 52-60, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-22778170

RESUMO

The mantle of dead organic material ("canopy soil") associated with the mats of vascular and nonvascular epiphytes found on the branches of trees in the temperate rainforests along the southwestern coast of the South Island of New Zealand were examined for evidence of ectomycorrhizal fungi. DNA sequencing and cluster analysis were used to identify the taxa of fungi present in 74 root tips collected from the canopy soil microhabitat of three old growth Nothofagus menziesii trees in the South West New Zealand World Heritage Area. A diverse assemblage of ectomycorrhizal fungi was found to infect an extensive network of adventitious canopy roots of Nothofagus menziesii in this forest, including 14 phylotypes from nine genera of putative ectomycorrhizal fungi. Seven of the genera identified previously were known to form ectomycorrhizas with terrestrial roots of Nothofagus: Cortinarius, Russula, Cenococcum, Thelephora/Tomentella, Lactarius and Laccaria; two, Clavulina and Leotia, previously have not been reported forming ectomycorrhizas with Nothofagus. Canopy ectomycorrhizas provide an unexpected means for increased host nutrition that may have functional significance in some forest ecosystems. Presumably, canopy ectomycorrhizas on host adventitious roots circumvent the tree-ground-soil nutrient cycle by accessing a wider range of nutrients directly in the canopy than would be possible for non-mycorrhizal or arbuscular mycorrhizal canopy roots. In this system, both host and epiphytes would seem to be in competition for the same pool of nutrients in canopy soil.


Assuntos
Micorrizas/isolamento & purificação , Árvores/microbiologia , Biodiversidade , Ecossistema , Fungos , Dados de Sequência Molecular , Micorrizas/classificação , Micorrizas/genética , Nova Zelândia
13.
JMIR Mhealth Uhealth ; 11: e47043, 2023 11 23.
Artigo em Inglês | MEDLINE | ID: mdl-37995121

RESUMO

BACKGROUND: There are more than 350,000 digital health interventions (DHIs) in the app stores. To ensure that they are effective and safe to use, they should be assessed for compliance with best practice standards. OBJECTIVE: The objective of this paper was to examine and compare the compliance of DHIs with best practice standards and adherence to user experience (UX), professional and clinical assurance (PCA), and data privacy (DP). METHODS: We collected assessment data from 1574 DHIs using the Organisation for the Review of Care and Health Apps Baseline Review (OBR) assessment tool. As part of the assessment, each DHI received a score out of 100 for each of the abovementioned areas (ie, UX, PCA, and DP). These 3 OBR scores are combined to make up the overall ORCHA score (a proxy for quality). Inferential statistics, probability distributions, Kruskal-Wallis, Wilcoxon rank sum test, Cliff delta, and Dunn tests were used to conduct the data analysis. RESULTS: We found that 57.3% (902/1574) of the DHIs had an Organisation for the Review of Care and Health Apps (ORCHA) score below the threshold of 65. The overall median OBR score (ORCHA score) for all DHIs was 61.5 (IQR 51.0-73.0) out of 100. A total of 46.2% (12/26) of DHI's health care domains had a median equal to or above the ORCHA threshold score of 65. For the 3 assessment areas (UX, DP, and PCA), DHIs scored the highest for the UX assessment 75.2 (IQR 70.0-79.6), followed by DP 65.1 (IQR 55.0-73.4) and PCA 49.6 (IQR 31.9-76.1). UX scores had the least variance (SD 13.9), while PCA scores had the most (SD 24.8). Respiratory and urology DHIs were consistently highly ranked in the National Institute for Health and Care Excellence Evidence Standards Framework tiers B and C based on their ORCHA score. CONCLUSIONS: There is a high level of variability in the ORCHA scores of DHIs across different health care domains. This suggests that there is an urgent need to improve compliance with best practices in some health care areas. Possible explanations for the observed differences might include varied market maturity and commercial interests within the different health care domains. More investment to support the development of higher-quality DHIs in areas such as ophthalmology, allergy, women's health, sexual health, and dental care may be needed.


Assuntos
Oftalmologia , Análise de Dados Secundários , Humanos , Feminino , Análise de Dados , Instalações de Saúde , Privacidade
14.
JTO Clin Res Rep ; 4(1): 100440, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36590015

RESUMO

Introduction: Single-agent monoclonal antibody therapy against programmed death-ligand 1 (PD-L1) has modest effects in malignant pleural mesothelioma. Radiation therapy can enhance the antitumor effects of immunotherapy. Nevertheless, the safety of combining anti-PD-L1 therapy with stereotactic body radiation therapy (SBRT) is unknown. We present the results of a phase 1 trial to evaluate the safety of the anti-PD-L1 antibody avelumab plus SBRT in patients with malignant pleural mesothelioma. Methods: This was a single-arm, investigator-initiated trial in patients who progressed on prior chemotherapy. Avelumab was delivered every other week, and SBRT was delivered to one lesion in three to five fractions (minimum of 30 Gy) followed by continuation of avelumab up to 24 months or until disease progression. The primary end point of the study was safety on the basis of grade 3+ nonhematologic adverse events (AEs) within 3 months of SBRT. Results: Thirteen assessable patients received a median of seven cycles (range: 2-26 cycles) of avelumab. There were 27 grade 1, 17 grade 2, four grade 3, and no grade 4 or 5 avelumab-related AEs. The most common were infusion-related allergic reactions (n = 6), anorexia or weight loss (n = 6), fatigue (n = 6), thyroid disorders (n = 5), diarrhea (n = 3), and myalgia or arthralgias (n = 3). There were 10 grade 1, four grade 2, one grade 3, and no grade 4 or 5 SBRT-related AEs. The most common were diarrhea (n = 3), chest pain/myalgia (n = 2), fatigue (n = 2), cough (n = 2), dyspnea (n = 2), and nausea/vomiting (n = 2). Conclusions: Combination avelumab plus SBRT seems tolerable on the basis of the prespecified toxicity end points of the first stage of this Simon two-stage design phase 1 study.

15.
Sci Total Environ ; 813: 152646, 2022 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-34968586

RESUMO

Seagrasses are considered indicators of anthropogenic impact but surprisingly little is known about their temporal and spatial dynamics in impacted seascapes. In this study, we used three decades of Landsat imagery (1988-2018) off the coast of Adelaide, South Australia, to investigate how seagrass cover over 501 km2 responds to changes in land-based inputs, including breakpoints in system trajectory and associated timelags, and the identification of vulnerable meadows. Field data was used to help train benthic classification of summer imagery and define its accuracy. Temporal dynamics of seagrass cover were investigated in relation to annual and multi-year nitrogen and suspended solids loads. Spatial dynamics were inferred from maps of benthic cover persistence and trajectory for each decade. The region experienced a net regrowth of some 11,000 ha of seagrasses since the early 2000s, with the initial large-scale recruitment visible in the imagery 6 years after the closure of sludge outfalls. Seagrass expansion occurred primarily in deeper waters (>10 m) of the central coast and at the seaward edge of the distribution. Recovery continued until 2011 assisted by a window of opportunity created by a decade-long drought and further reductions in nitrogen loads from wastewater treatment plants and industry. Localized seagrass losses however continued to be observed as a result of either permanent or transient increases in suspended solids loads. Seagrass area in the central coast was well correlated (r2 = 0.88) with 5-year running averages of nitrogen and suspended solids loads. Meadows particularly vulnerable to changes in land-based discharges were located at the edges of the distribution, along erosional scarps and at depths >10 m south of the Torrens River. These areas were identified as useful indicators of seagrass status. Overall, seagrass persistence expanded from 48 to 69% of the mapped area, with the region now mostly covered by stable seagrasses.


Assuntos
Ecossistema , Nitrogênio , Estações do Ano , Austrália do Sul
16.
Sci Rep ; 11(1): 4182, 2021 02 18.
Artigo em Inglês | MEDLINE | ID: mdl-33603192

RESUMO

Seagrasses are regarded as indicators and first line of impact for anthropogenic activities affecting the coasts. The underlying mechanisms driving seagrass cover however have been mostly studied on small scales, making it difficult to establish the connection to seagrass dynamics in an impacted seascape. In this study, hyperspectral airborne imagery, trained from field surveys, was used to investigate broadscale seagrass cover and genus distribution along the coast of Adelaide, South Australia. Overall mapping accuracy was high for both seagrass cover (98%, Kappa = 0.93), and genus level classification (85%, Kappa = 0.76). Spectral separability allowed confident genus mapping in waters up to 10 m depth, revealing a 3.5 ratio between the cover of the dominant Posidonia and Amphibolis. The work identified the absence of Amphibolis in areas historically affected by anthropogenic discharges, which occasionally contained Posidonia and might be recovering. The results suggest hyperspectral imagery as a useful tool to investigate the interplay between seagrass cover and genus distribution at large spatial scales.

17.
J Thorac Oncol ; 16(7): 1149-1165, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-33839363

RESUMO

INTRODUCTION: NRG1 rearrangements produce chimeric ligands that subvert the ERBB pathway to drive tumorigenesis. A better understanding of the signaling networks that mediate transformation by NRG1 fusions is needed to inform effective therapeutic strategies. Unfortunately, this has been hampered by a paucity of patient-derived disease models that faithfully recapitulate this molecularly defined cancer subset. METHODS: Patient-derived xenograft (PDX) and cell line models were established from NRG1-rearranged lung adenocarcinoma samples. Transcriptomic, proteomic, and biochemical analyses were performed to identify activated pathways. Efficacy studies were conducted to evaluate HER3- and MTOR-directed therapies. RESULTS: We established a pair of PDX and cell line models of invasive mucinous lung adenocarcinoma (LUAD) (LUAD-0061AS3, SLC3A2-NRG1), representing the first reported paired in vitro and in vivo model of NRG1-driven tumors. Growth of LUAD-0061AS3 models was reduced by the anti-HER3 antibody GSK2849330. Transcriptomic profiling revealed activation of the MTOR pathway in lung tumor samples with NRG1 fusions. Phosphorylation of several MTOR effectors (S6 and 4EBP1) was higher in LUAD-0061AS3 cells compared with human bronchial epithelial cells and the breast cancer cell line MDA-MB-175-VII (DOC4-NRG1 fusion). Accordingly, LUAD-0061AS3 cells were more sensitive to MTOR inhibitors than MDA-MB-175-VII cells and targeting the MTOR pathway with rapamycin blocked growth of LUAD-0061AS3 PDX tumors in vivo. In contrast, MDA-MB-175-VII breast cancer cells had higher MAPK pathway activation and were more sensitive to MEK inhibition. CONCLUSIONS: We identify the MTOR pathway as a candidate vulnerability in NRG1 fusion-positive lung adenocarcinoma that may warrant further preclinical evaluation, with the eventual goal of finding additional therapeutic options for patients in whom ERBB-directed therapy fails. Moreover, our results uncover heterogeneity in downstream oncogenic signaling among NRG1-rearranged cancers, possibly tumor type-dependent, the therapeutic significance of which requires additional investigation.


Assuntos
Neoplasias Pulmonares , Proteômica , Linhagem Celular Tumoral , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Neuregulina-1/genética , Proteínas de Fusão Oncogênica/genética , Serina-Treonina Quinases TOR
18.
Artigo em Inglês | MEDLINE | ID: mdl-34250398

RESUMO

Patients with EGFR-mutant lung cancer have no approved targeted therapies after disease progression on first-line osimertinib, a third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI). Preclinical studies suggest that tumors with both EGFR-sensitizing alteration and acquired second-site EGFR resistance alterations after treatment with osimertinib retain sensitivity to second-generation EGFR TKIs. We hypothesized that dacomitinib, a pan-human epidermal growth factor receptor TKI, may be effective in this setting. METHODS: In this phase II study, patients who had progressed on first-line osimertinib were treated with dacomitinib 45 mg orally daily until disease progression or intolerability. The primary end point was objective response rate. RESULTS: We enrolled 12 patients. Two partial responses were documented (17% objective response rate; 95% CI, 5 to 45). The median progression-free survival was 1.8 months (95% CI, 1.6 to not reached). One patient with an original sensitizing EGFR G719A mutation and one patient without molecular testing available had partial responses, whereas 0 of the 3 patients with second-site acquired EGFR resistance mutations (two C797S and one G724S) met the response criteria. The patient with EGFR G719A has an ongoing response at 17 months, which exceeds prior time on osimertinib (11 months). CONCLUSION: In the first trial evaluating a second-generation EGFR TKI after first-line third-generation osimertinib, we found that dacomitinib after disease progression on osimertinib has limited benefit.


Assuntos
Acrilamidas/uso terapêutico , Compostos de Anilina/uso terapêutico , Antineoplásicos/uso terapêutico , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Mutação , Quinazolinonas/uso terapêutico , Idoso , Idoso de 80 Anos ou mais , Progressão da Doença , Receptores ErbB/genética , Feminino , Humanos , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Projetos Piloto , Estudos Prospectivos , Retratamento
19.
BMJ Open ; 11(9): e049217, 2021 09 06.
Artigo em Inglês | MEDLINE | ID: mdl-34489282

RESUMO

INTRODUCTION: Early phase cancer clinical trials have become increasingly complicated in terms of patient selection and trial procedures-this is reflected in the increasing length of participant information sheets (PIS). Informed consent for early phase clinical trials has been contentious due to the potential ethical issues associated with performing experimental research on a terminally ill population which has exhausted standard treatment options. Empirical studies have demonstrated significant gaps in patient understanding regarding the nature and intent of these trials. This study aims to test whether enhanced informed consent for patient education can improve patient scores on a validated questionnaire testing clinical trial comprehension. METHODS AND ANALYSIS: This is a randomised controlled trial that will allocate patients who are eligible to participate in one of four investigator-initiated clinical trials at the Royal Marsden Drug Development Unit to either a standard arm or an experimental arm, stratified by age and educational level. The standard arm will involve the full length trial PIS, followed by electronic or paper administration of the Quality of Informed Consent Questionnaire Parts A and B (QuIC-A and QuIC-B). The experimental arm will involve the full length trial PIS, exposure to a two-page study aid and 10 online educational videos, followed by administration of the QuIC-A and QuIC-B. The primary endpoint will be the difference (using a one-sided two-sample t-test) in the QuIC-A score, which measures objective understanding, between the standard and experimental arm. Accrual target is at least 17 patients per arm to detect an 8 point difference (80% power, alpha 0.05). ETHICS AND DISSEMINATION: Ethics approval was granted by the National Health Service Health Research Authority on 15 June 2020-IRAS Project ID 277065, Protocol Number CCR5165, REC Reference 20/EE/0155. Results will be disseminated via publication in a relevant journal. TRIAL REGISTRATION NUMBER: NCT04407676; Pre-results.


Assuntos
COVID-19 , Neoplasias , Humanos , Consentimento Livre e Esclarecido , Neoplasias/terapia , Ensaios Clínicos Controlados Aleatórios como Assunto , SARS-CoV-2 , Medicina Estatal , Resultado do Tratamento
20.
Environ Sci Technol ; 44(23): 9055-61, 2010 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-21049989

RESUMO

Surface water sources are increasingly subject to proliferation of toxic cyanobacteria. Direct chlorination of source water containing toxic cyanobacterial cells for different treatment purposes might cause cell damage and toxin release. There is limited information available on chlorination of saxitoxins (STXs: saxitoxin, C-toxins, and gonyautoxins) produced by Anabaena circinalis. This work: (1) investigated the impact of chlorination on cell lysis and toxin/odor compound release in natural waters; (2) assessed the rates of chlorination of total STXs, and (3) estimated apparent rate constants for STX oxidation in ultrapure and natural waters. With a chlorine exposure (CT) value of 7.0 mg x min/L all cells lost viability causing toxin release. Cell-membrane damage occurred faster than released STXs oxidation. All saxitoxin and more than 95% of other STX analogues were subsequently oxidized. Kinetic analysis of the oxidation of STX analogues revealed significant differences in the susceptibility to chlorine, saxitoxin being the easiest to oxidize. Also, concentrations of trihalomethanes, haloacetic acids, and N-nitrosodimethylamine as chlorination byproducts were respectively <50 µg/L and 11 ng/L even at the highest CT value (50.3 mg x min/L).


Assuntos
Anabaena/metabolismo , Desinfecção , Halogenação , Saxitoxina/metabolismo , Poluentes Químicos da Água/análise , Anabaena/efeitos dos fármacos , Anabaena/patogenicidade , Oxirredução , Saxitoxina/análise , Saxitoxina/toxicidade , Purificação da Água
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