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1.
Analyst ; 2024 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-38712606

RESUMO

Plant hormones are important in the control of physiological and developmental processes including seed germination, senescence, flowering, stomatal aperture, and ultimately the overall growth and yield of plants. Many currently available methods to quantify such growth regulators quickly and accurately require extensive sample purification using complex analytic techniques. Herein we used ultra-performance liquid chromatography-high-resolution mass spectrometry (UHPLC-HRMS) to create and validate the prediction of hormone concentrations made using attenuated total reflection Fourier-transform infrared (ATR-FTIR) spectral profiles of both freeze-dried ground leaf tissue and extracted xylem sap of Japanese knotweed (Reynoutria japonica) plants grown under different environmental conditions. In addition to these predictions made with partial least squares regression, further analysis of spectral data was performed using chemometric techniques, including principal component analysis, linear discriminant analysis, and support vector machines (SVM). Plants grown in different environments had sufficiently different biochemical profiles, including plant hormonal compounds, to allow successful differentiation by ATR-FTIR spectroscopy coupled with SVM. ATR-FTIR spectral biomarkers highlighted a range of biomolecules responsible for the differing spectral signatures between growth environments, such as triacylglycerol, proteins and amino acids, tannins, pectin, polysaccharides such as starch and cellulose, DNA and RNA. Using partial least squares regression, we show the potential for accurate prediction of plant hormone concentrations from ATR-FTIR spectral profiles, calibrated with hormonal data quantified by UHPLC-HRMS. The application of ATR-FTIR spectroscopy and chemometrics offers accurate prediction of hormone concentrations in plant samples, with advantages over existing approaches.

2.
Appl Opt ; 62(15): 4074-4079, 2023 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-37706719

RESUMO

Narrow bandpass filters (NBFs), which are designed to accept a narrow wavelength range and simultaneously reject a much wider range, show great potential in applications such as spectral imaging, lidar detection, fluorescence microscopy, and others. In this paper, we propose and numerically simulate NBF technology for infrared (IR) optical applications. The filter is a combination of plasmonic nanostructures and improved induced transmission layers. The operating wavelength range is from 1360 to 5000 nm [short wave mid-infrared radiation(SWM-IR)], with a FWHM of less than 10 nm and maximum optical density of around 10. Therefore, our SWM-IR hybrid filter can distinguish much smaller differences in terms of spectrum information and reduce the background noise level even if using an optical amplifier.

3.
PLoS One ; 17(7): e0271370, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35802594

RESUMO

[This corrects the article DOI: 10.1371/journal.pone.0261742.].

4.
Support Care Cancer ; 30(5): 4417-4428, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35106657

RESUMO

PURPOSE: Identification of unmet needs in person centred and supportive care could be limited by differences in experience across specific cancer populations. Using the experiences of people with lung cancer, we assess distinctions according to demographic and clinical characteristics. METHODS: The English Cancer Patient Experience Survey was linked to the national cancer registry. The primary outcome was experience of the lung cancer pathway when assessed in multi-question models developed with item response theory. Secondary outcomes were experience by treatment received and in separate dimensions of the care pathway: up to diagnosis, treatment information, and staff support. RESULTS: Responses from 15,967 adults with a lung cancer diagnosis between 2009 and 2015 were included. Positive experiences were more likely to be reported by people aged between 65 and 80 (adjusted coefficient 0.08, 95%CI 0.05;0.11), those living in the most deprived areas (adjusted coefficient 0.10, 95%CI 0.05;0.14), diagnosed at lung cancer stage IIA-B (adjusted coefficient 0.09, 95%CI 0.04;0.14), and those diagnosed through inpatient elective admissions (adjusted coefficient 0.17, 95%CI 0.07;0.28). Specific experiences differed across dimensions of care and within lung cancer treatment groups. CONCLUSIONS: Experiences differed according to gender and ethnicity, supporting previous observations in cancer. In contrast to previous studies, people with lung cancer were more likely to report positive pathway experiences at older ages, living in more deprived areas, or diagnosed after stage I, all frequently associated with worse clinical outcomes. The distinct observations in lung cancer specific analyses suggest potential unmet needs, such as in early stage disease and younger age groups.


Assuntos
Neoplasias Pulmonares , Motivação , Adulto , Idoso , Idoso de 80 Anos ou mais , Humanos , Neoplasias Pulmonares/terapia , Avaliação de Resultados da Assistência ao Paciente , Sistema de Registros , Inquéritos e Questionários
5.
PLoS One ; 17(1): e0261742, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-34995300

RESUMO

Extreme weather and globalisation leave our climate vulnerable to invasion by alien species, which have negative impacts on the economy, biodiversity, and ecosystem services. Rapid and accurate identification is key to the control of invasive alien species. However, visually similar species hinder conservation efforts, for example hybrids within the Japanese Knotweed complex.We applied the novel method of ATR-FTIR spectroscopy combined with chemometrics (mathematics applied to chemical data) to historic herbarium samples, taking 1580 spectra in total. Samples included five species from within the interbreeding Japanese Knotweed complex (including three varieties of Japanese Knotweed), six hybrids and five species from the wider Polygonaceae family. Spectral data from herbarium specimens were analysed with several chemometric techniques: support vector machines (SVM) for differentiation between plant types, supported by ploidy levels; principal component analysis loadings and spectral biomarkers to explore differences between the highly invasive Reynoutria japonica var. japonica and its non-invasive counterpart Reynoutria japonica var. compacta; hierarchical cluster analysis (HCA) to investigate the relationship between plants within the Polygonaceae family, of the Fallopia, Reynoutria, Rumex and Fagopyrum genera.ATR-FTIR spectroscopy coupled with SVM successfully differentiated between plant type, leaf surface and geographical location, even in herbarium samples of varying age. Differences between Reynoutria japonica var. japonica and Reynoutria japonica var. compacta included the presence of two polysaccharides, glucomannan and xyloglucan, at higher concentrations in Reynoutria japonica var. japonica than Reynoutria japonica var. compacta. HCA analysis indicated that potential genetic linkages are sometimes masked by environmental factors; an effect that can either be reduced or encouraged by altering the input parameters. Entering the absorbance values for key wavenumbers, previously highlighted by principal component analysis loadings, favours linkages in the resultant HCA dendrogram corresponding to expected genetic relationships, whilst environmental associations are encouraged using the spectral fingerprint region.The ability to distinguish between closely related interbreeding species and hybrids, based on their spectral signature, raises the possibility of using this approach for determining the origin of Japanese knotweed infestations in legal cases where the clonal nature of plants currently makes this difficult and for the targeted control of species and hybrids. These techniques also provide a new method for supporting biogeographical studies.


Assuntos
Espécies Introduzidas , Ploidias , Polygonaceae/classificação , Polygonaceae/crescimento & desenvolvimento , Polygonaceae/genética , Espectroscopia de Infravermelho com Transformada de Fourier
6.
Int J Nurs Stud Adv ; 4: 100077, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38745624

RESUMO

Introduction: More than 2,700 people are diagnosed with mesothelioma each year in the UK. Survival from mesothelioma is poor and to ensure service users' perspectives are incorporated in designing the most effective strategies to improve healthcare in England, the English Cancer Patient Experience Survey (CPES) is carried out annually in people diagnosed with cancer. We assessed whether the mesothelioma population responding to the English CPES is representative of the national mesothelioma population. Method: Data from all people in England from the National Cancer Registry defined as having an incident mesothelioma diagnosis (2009-2015) were included. Data were linked across multiple sources including CPES. Using multivariable logistic regression, clinical and sociodemographic characteristics were compared between CPES respondents with mesothelioma and all people with mesothelioma in England. Results: We identified 15,587 people diagnosed with mesothelioma, of which 1,597 (10.3%) were included in CPES. Adjusted odds ratios showed that representation in CPES decreased with older age, later stage, worse performance status, multiple comorbidities or emergency presentation at diagnosis. Gender was reasonably represented, although people with non-white ethnicity and from more deprived socioeconomic groups were underrepresented. lung cancer nurse specialist assessment was not associated with inclusion in CPES, however, having a lung cancer nurse specialist present at diagnosis was. Representation in CPES was highest for people who had chemo-radiotherapy (fully adjusted odds ratio 6.52 (95% confidence interval 5.34-7.96). Conclusion: Responses were included across all sociodemographic and clinical groups, but there was unbalanced representation when compared with the national mesothelioma population. Patients who do not receive anti-cancer treatment are particularly under-represented. It is important to consider the impact of person characteristics on CPES representation when using cancer experiences to plan service management.

7.
BMC Plant Biol ; 21(1): 522, 2021 Nov 09.
Artigo em Inglês | MEDLINE | ID: mdl-34753418

RESUMO

BACKGROUND: Japanese knotweed (R. japonica var japonica) is one of the world's 100 worst invasive species, causing crop losses, damage to infrastructure, and erosion of ecosystem services. In the UK, this species is an all-female clone, which spreads by vegetative reproduction. Despite this genetic continuity, Japanese knotweed can colonise a wide variety of environmental habitats. However, little is known about the phenotypic plasticity responsible for the ability of Japanese knotweed to invade and thrive in such diverse habitats. We have used attenuated total reflection Fourier-transform infrared (ATR-FTIR) spectroscopy, in which the spectral fingerprint generated allows subtle differences in composition to be clearly visualized, to examine regional differences in clonal Japanese knotweed. RESULTS: We have shown distinct differences in the spectral fingerprint region (1800-900 cm- 1) of Japanese knotweed from three different regions in the UK that were sufficient to successfully identify plants from different geographical regions with high accuracy using support vector machine (SVM) chemometrics. CONCLUSIONS: These differences were not correlated with environmental variations between regions, raising the possibility that epigenetic modifications may contribute to the phenotypic plasticity responsible for the ability of R. japonica to invade and thrive in such diverse habitats.


Assuntos
Fallopia japonica/crescimento & desenvolvimento , Espectroscopia de Infravermelho com Transformada de Fourier , Adaptação Fisiológica/genética , Clima , Meio Ambiente , Fallopia japonica/química , Fallopia japonica/genética , Espécies Introduzidas , Filogeografia , Solo
8.
JTO Clin Res Rep ; 2(6): 100176, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-34590024

RESUMO

INTRODUCTION: Optimal management of people with advanced NSCLC depends on accurate identification of predictive markers. Yet, real-world data in this setting are limited. We describe the impact, timeliness, and outcomes of molecular testing for patients with advanced NSCLC and good performance status in England. METHODS: In collaboration with Public Health England, patients with stages IIIB to IV NSCLC, with an Eastern Cooperative Oncology Group performance status of 0 to 2, in England, between June 2017 and December 2017, were identified. All English hospitals were invited to record information. RESULTS: A total of 60 of 142 invited hospitals in England participated in this study and submitted data on 1157 patients. During the study period, 83% of patients with advanced adenocarcinoma underwent molecular testing for three recommended predictive biomarkers (EGFR, ALK, and programmed death-ligand 1). A total of 80% of patients with nonsquamous carcinomas on whom biomarker testing was performed had adequate tissue for analysis on initial sampling. First-line treatment with a tyrosine kinase inhibitor was received by 71% of patients with adenocarcinoma and a sensitizing EGFR mutation and by 59% of those with an ALK translocation. Of patients with no driver mutation and a programmed death-ligand 1 expression of greater than or equal to 50%, 47% received immunotherapy. CONCLUSIONS: We present a comprehensive data set for molecular testing in England. Although molecular testing is well established in England, timeliness and uptake of targeted therapies should be improved.

9.
Int J Ment Health Nurs ; 30(6): 1630-1639, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34342099

RESUMO

The Nursing and Midwifery Board of Australia's Code of Conduct for Nurses sets out the professional behaviour and conduct expectations for nurses in all practice settings. The publication of a revised version in 2018, which included expectations related to culturally safe and respectful practice and Aboriginal and Torres Strait Islander Peoples' health, caused reverberations beyond the profession of nursing. A controversy that the changes required nurses to verbally apologize for being white before their interactions with Aboriginal and Torres Strait Islander people gained the attention of the mainstream media. This interpretation, which came from outside nursing, was disputed by the Board. Challenged by these events, the authors were interested in understanding the actual impacts of the changes from the perspectives of nurses in practice. This research, carried out nearly three years after publication, has focused specifically on the speciality of mental health nurses in this context. The objective of this research was to undertake a social analysis focused on the impact that changes in the Code have had on the culture of mental health nursing utilizing a qualitative methodology. Eight mental health nurses were interviewed. The research found that there was little evidence of any impact on mental health nursing practice. Many of the participants were unaware of the amendments to the Code, whilst those nurses who were aware did not perceive that it had led to any real change within mental health nursing or service delivery.


Assuntos
Serviços de Saúde do Indígena , Enfermeiras e Enfermeiros , Enfermagem Psiquiátrica , Humanos , Saúde Mental , Havaiano Nativo ou Outro Ilhéu do Pacífico
10.
Nanomaterials (Basel) ; 11(8)2021 Aug 23.
Artigo em Inglês | MEDLINE | ID: mdl-34443976

RESUMO

Dichroic circular polarizers (DCP) represent an important group of optical filters that transfer only that part of the incident light with the desired polarization state and absorb the remainder. However, DCPs are usually bulky and exhibit significant optical loss. Moreover, the integration of these kinds of DCP devices can be difficult and costly as different compositions of chemicals are needed to achieve the desired polarization status. Circular polarizers based on metasurfaces require only thin films in the order of hundreds of nanometers but are limited by their sensitivity to angle of incidence. Furthermore, few existing solutions offer broadband operation in the visible range. By using computational simulations, this paper proposes and analyses a plasmonic DCP structure operating in the visible, from 400 nm to 700 nm which overcomes these drawbacks. The resulting circular dichroism transmission (CDT) is more than 0.9, and the maximum transmission efficiency is greater than 78% at visible wavelengths. These CDT characteristics are largely independent of angle of incidence up to angles of 80 degrees.

11.
Contemp Nurse ; 57(1-2): 140-156, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33989117

RESUMO

Background: For nearly thirty years, significant concerns have been raised about the public-provided mental health services for Aboriginal and Torres Strait Islander peoples. Staff have been identified as having little understanding of Indigenous culture, and this had resulted in inappropriate treatment. In attempting to understand what specialist knowledge exists to guide mental health nursing practice with Aboriginal and Torres Strait Islander peoples, the authors have turned to published peer-reviewed literature.Methods: The approach chosen to explore this area was an integrative review. This provided a method to identify, analyse, and synthesise a wide range of literature.Results: The available evidence points to the need that treatment planning must be focused on the promotion of social and emotional wellbeing and not simply the treatment of symptoms. It also emphasises the importance of cultural safety informed by awareness and understanding of social, cultural and historical factors that can impact the health and treatment of Aboriginal and Torres Strait Islander peoples. Within the literature, staff reported difficulty in understanding how knowledge about social and emotional wellbeing could translate into practice. Nurses working in mental health contexts reported not feeling adequately prepared for, or confident in this area of practice.Conclusions: There is a paucity of current literature on mental health nursing practice for Aboriginal and Torres Strait Islander peoples, with the literature available not providing clear guidance for effective and meaningful practice.


Assuntos
Enfermagem Psiquiátrica , Atenção à Saúde , Humanos , Saúde Mental , Havaiano Nativo ou Outro Ilhéu do Pacífico
12.
Int J Nurs Stud ; 118: 103718, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32859375

RESUMO

BACKGROUND: Cancer nurse specialists are advanced practitioners who offer continuity of care and expert support for people diagnosed with specific cancers. Health Education England's Cancer Workforce Plan prioritises expansion of cancer nurse specialist numbers by 2021 as part of the Cancer Taskforce Strategy for England. OBJECTIVE: To assess whether working practices of advanced practice specialist nurses are associated with clinical outcomes for people with lung cancer. METHODS: Adults with non-small cell lung cancer followed from 30 days post-diagnosis in English secondary care were obtained from the English National Lung Cancer Audit, 2007 to 2011. A national survey of lung cancer nurse specialists provided information on self-reported working practices. Mortality and unplanned admissions from 30 days to 12 months post diagnosis were respectively analysed using Cox and Poisson regression. Outcomes were assessed according to patients' receipt of initial assessments by a lung cancer nurse specialist and according to trust-level reported working practices. Regression models were adjusted for individual sociodemographic and clinical characteristics, error adjusted for intracorrelations within regional cancer networks, and presented separately according to patients' treatment pathways (surgery, chemotherapy, radiotherapy, or no anti-cancer therapy). RESULTS: Data for 108,115 people with lung cancer were analysed and associations with mortality and unplanned admissions were infrequent. Among people receiving only radiotherapy, however, the hazard for death was 17% lower among those who received an assessment by a lung cancer nurse specialist, compared with no assessment (hazard ratio = 0.83, 95% confidence interval 0.73-0.94; p = 0.003). The hazard was also lower among those receiving surgery (hazard ratio = 0.91, 0.84-0.99; p = 0.028). Among those receiving radiotherapy, nurse specialists' reported confidence within multidisciplinary team settings was associated with a lower risk of death (hazard ratio = 0.88, 0.78-1.00; p = 0.049) and a lower rate of unplanned cancer-related admissions (incidence rate ratio = 0.83, 0.73-0.95; p = 0.007). Lung cancer nurse specialist assessments before/at diagnosis, were associated with a 5% lower rate of unplanned admissions, compared to when assessments occurred after diagnosis. CONCLUSION: The contribution of nurse specialist working practices was occasionally associated with better outcomes for people with lung cancer. These were not limited to a single treatment pathway, but do indicate discrete relationships within pathways. Our study provides initial measures of overall lung cancer nurse specialist working practices at trusts, however, more detailed studies with longitudinal measurement of lung cancer nurse specialist-patient interaction are needed to better ascertain impacts on long-term patient outcomes. The findings highlight opportunities for potential improvement in effectiveness of service and care management.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Enfermeiros Especialistas , Adulto , Inglaterra , Humanos , Neoplasias Pulmonares/terapia , Estudos Retrospectivos
13.
J Psychosoc Nurs Ment Health Serv ; 58(11): 15-18, 2020 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-33119117

RESUMO

Culture is a crucial factor in understanding variations in stigma experiences among young people (age ≤25 years). Cultural beliefs influence the range of social responses that mental health issues elicit, including forms of treatment and role expectations of carers. The current article explores the influence that stigma and culture can have on young people with mental illness. It highlights that it is impossible for nurses to be cognizant of all belief systems related to mental illness. Hence, cultural safety is an approach that can facilitate engagement with the nuances of a young person's culture and provide the foundations of appropriate care. [Journal of Psychosocial Nursing and Mental Health Services, 58(11), 15-18.].


Assuntos
Cultura , Transtornos Mentais/psicologia , Enfermagem Psiquiátrica , Estigma Social , Adolescente , Adulto , Humanos , Serviços de Saúde Mental , Adulto Jovem
14.
Br J Cancer ; 123(11): 1588-1589, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32958826

RESUMO

The UK has the highest incidence of mesothelioma in the world, but services vary across the country partly due to uneven geographical distribution of cases. The Mesothelioma UK-funded national organisational audit has highlighted challenges in accessing diagnostic procedures such as thoracoscopy, as well as identifying examples of best practice, including access to clinical trials and specialist therapeutic procedures. To ensure equitable and optimal patient care, cancer alliances should have established referral pathways to specialist multidisciplinary team (MDT) services for discussion of all mesothelioma patients.


Assuntos
Oncologia/normas , Mesotelioma/terapia , Padrão de Cuidado , Humanos , Reino Unido
15.
Lung Cancer ; 140: 27-34, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31846785

RESUMO

OBJECTIVES: Healthcare systems increasingly recognise the importance of service users' perspectives for improving care organisation and delivery. The English Cancer Patient Experience Survey (CPES) is carried out annually, however, its representativeness within cancer types is unknown. We have explored if the CPES results are representative of people with lung cancer. MATERIALS AND METHODS: We linked cancer registry data across multiple sources to assess how CPES represents sociodemographic and clinical characteristics of the National Lung Cancer Audit population, accounting for post-sampling mortality bias. Multivariable logistic regression was used to compare people included and not included in CPES. RESULTS: Of 240,375 people diagnosed (2009-2015), 15,967 (7 %) were included in CPES. Gender and ethnicity were reasonably represented, as were sociodemographic and clinical groupings, although more received anti-cancer treatment (96 % of CPES respondents vs. 56 % of patients nationally; adjusted odds ratio = 10.3, 95 % confidence interval 9.4-11.2 for any anti-cancer treatment) with chemotherapy most over-represented, followed by surgery and then radiotherapy. CPES under-represented older, more socioeconomically deprived, and certain clinical groups, including those with worse performance status, multiple comorbidities, and diagnosis via emergency presentation. CONCLUSION: CPES includes patients across the sociodemographic and clinical spectrum indicating its value for research and service planning. Unbalanced representation of incident lung cancer cases is a limitation that must be considered in context of using CPES findings to implement service changes. Although half the national lung cancer population who received no anti-cancer treatment do not have their experiences represented, the strength of this dataset is in providing detailed comparisons of patient experiences across different treatment groups.


Assuntos
Tumor Carcinoide/epidemiologia , Carcinoma Pulmonar de Células não Pequenas/epidemiologia , Neoplasias Pulmonares/epidemiologia , Auditoria Médica/estatística & dados numéricos , Sistema de Registros/estatística & dados numéricos , Carcinoma de Pequenas Células do Pulmão/epidemiologia , Idoso , Idoso de 80 Anos ou mais , Tumor Carcinoide/patologia , Tumor Carcinoide/terapia , Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma Pulmonar de Células não Pequenas/terapia , Terapia Combinada , Comorbidade , Feminino , Seguimentos , Humanos , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/terapia , Masculino , Prognóstico , Carcinoma de Pequenas Células do Pulmão/patologia , Carcinoma de Pequenas Células do Pulmão/terapia , Inquéritos e Questionários , Taxa de Sobrevida , Reino Unido/epidemiologia
16.
Thorax ; 75(3): 237-243, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-31879316

RESUMO

BACKGROUND: Approximately 15%-20% of all non-small cell lung cancer (NSCLC) cases present with stage I disease. Surgical resection traditionally offers the best chance of a cure but some patients will not have this treatment due to older age, comorbidities or personal choice. Stereotactic ablative radiotherapy (SABR) has become an established curative intent treatment option for patients who are not selected for or do not choose surgery. The aim of this study is to compare survival at 90 days, 6 months, 1 year and 2 years for patients who received either lobectomy or SABR. METHODS: We used data from the 2015 National Lung Cancer Audit database and linked with Hospital Episode Statistics and the radiotherapy dataset to identify patients with NSCLC stage IA-IB and performance status (PS) 0-2 who underwent surgery or SABR treatment. We assessed the likelihood of death at 90 days, 6 months, 1 year and 2 year after diagnosis and procedure date to observe survival between two patient groups. RESULTS: We identified 2373 patients in our cohort, 476 of whom had SABR. The median difference between date of diagnosis and date of treatment for surgery patients was 17 days while for SABR patients it was 73 days. Increasing age and worsening PS were associated with having SABR rather than surgery. Survival between the two treatment modalities was similar early on but by 1-year people who had surgery did better than those who had SABR (adjusted ORs 2.12, 95% CI 1.35 to 2.31). This difference persisted at 2 years and when the analysis was restricted to patients aged <80 years and with PS 0 or 1 and stage IA only. CONCLUSION: Our analysis suggests that patients who have lobectomy have a better survival compared with SABR patients; however, we found considerable delays in patients receiving SABR which may contribute to poorer long-term outcomes with this treatment option. Reducing these delays should be a key focus in development and reorganisation of services.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/radioterapia , Carcinoma Pulmonar de Células não Pequenas/cirurgia , Neoplasias Pulmonares/radioterapia , Neoplasias Pulmonares/cirurgia , Pneumonectomia , Radiocirurgia , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Carcinoma Pulmonar de Células não Pequenas/patologia , Bases de Dados Factuais , Inglaterra , Feminino , Seguimentos , Indicadores Básicos de Saúde , Humanos , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Radiocirurgia/métodos , Taxa de Sobrevida , Fatores de Tempo , Tempo para o Tratamento
17.
Blood Adv ; 3(22): 3661-3673, 2019 11 26.
Artigo em Inglês | MEDLINE | ID: mdl-31751472

RESUMO

Acute myeloid leukemias (AML) harboring a constitutively active internal tandem duplication (ITD) mutation in the FMS-like kinase tyrosine kinase (FLT3) receptor are associated with poor patient prognosis. Despite initial clinical responses to FLT3 kinase inhibitors, patients eventually relapse. Mechanisms of resistance include the acquisition of secondary FLT3 mutations and protective stromal signaling within the bone marrow niche. Here we show that LAM-003, a prodrug of the heat shock protein 90 inhibitor LAM-003A, has cytotoxic activity against AML cell lines and primary samples harboring FLT3-ITD. LAM-003 regressed tumors in an MV-4-11 xenograft mouse model and extended survival in a MOLM-13 systemic model. LAM-003 displayed synergistic activity with chemotherapeutic drugs and FLT3 inhibitors, with the most robust synergy being obtained with venetoclax, a BCL-2 inhibitor. This finding was verified in a MOLM-13 systemic survival model in which the combination significantly prolonged survival compared with the single agents. Importantly, LAM-003 exhibited equipotent activity against FLT3 inhibitor-resistant mutants of FLT3, such as D835 or F691, in cytotoxic and FLT3 degradation assays. LAM-003 also retained potency in AML cells grown in stromal-conditioned media that were resistant to FLT3 inhibitors. Lastly, a genome-wide CRISPR screen revealed epigenetic regulators, including KDM6A, as determinants of LAM-003 sensitivity in AML cell lines, leading to the discovery of synergy with an EZH2 inhibitor. Collectively, these preclinical findings support the use of LAM-003 in FLT3-ITD patients with AML who no longer respond to FLT3 inhibitor therapy either as a single agent or in combination with drugs known to be active in AML.


Assuntos
Antineoplásicos/farmacologia , Resistencia a Medicamentos Antineoplásicos/genética , Duplicação Gênica , Leucemia Mieloide Aguda/genética , Inibidores de Proteínas Quinases/farmacologia , Tirosina Quinase 3 Semelhante a fms/genética , Animais , Antineoplásicos/uso terapêutico , Linhagem Celular Tumoral , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Sinergismo Farmacológico , Epigênese Genética , Regulação Leucêmica da Expressão Gênica/efeitos dos fármacos , Humanos , Leucemia Mieloide Aguda/tratamento farmacológico , Camundongos , Mutação , Inibidores de Proteínas Quinases/uso terapêutico
18.
Thorax ; 74(6): 546-550, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-30661021

RESUMO

INTRODUCTION: Data from the National Lung Cancer Audit (NLCA) often show variation in outcomes between lung cancer units which are not entirely explained by case mix. We explore the association between the organisation of services and patient outcome. METHODS: Details of service provision were collected via an electronic survey in June 2017. An overall organisational score derived from eleven key service factors from national lung cancer commissioning guidance was calculated for each organisation. The results for each hospital were linked to their patient outcome results from the 2015 NLCA cases. Multivariate logistic regression analysis was used to link the organisational score to patient outcomes. RESULTS: Lung cancer unit organisational audit scores varied from 0 to 11. Thirty-eight (29%) units had a score of 0-4, 64 (50%) had a score of 5-7 and 27 (21%) had a score of 8-11. Multivariate regression analysis revealed that, compared with an organisational score of 0-4, patients seen at units with a score of 8-11 had higher 1-year survival (adjusted OR (95% CI)=2.30 (1.04 to 5.08), p<0.001), higher curative-intent treatment rate (adjusted OR (95% CI)=1.62 (1.26 to 2.09), p<0.001) and greater likelihood of receiving treatment within 62 days (adjusted OR (95% CI)=1.49 (1.20 to 1.86), p<0.001). CONCLUSION: National variation in the provision of services and workforce remain. We provide evidence that adherence to the national lung commissioning guidance has the potential to improve patient outcomes within the current service structure.


Assuntos
Atenção à Saúde/normas , Fidelidade a Diretrizes , Neoplasias Pulmonares/terapia , Medicina , Avaliação de Resultados em Cuidados de Saúde , Idoso , Idoso de 80 Anos ou mais , Inglaterra , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Inquéritos e Questionários
19.
BMC Cancer ; 18(1): 1144, 2018 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-30458807

RESUMO

BACKGROUND: A minority of European countries have participated in international comparisons with high level data on lung cancer. However, the nature and extent of data collection across the continent is simply unknown, and without accurate data collection it is not possible to compare practice and set benchmarks to which lung cancer services can aspire. METHODS: Using an established network of lung cancer specialists in 37 European countries, a survey was distributed in December 2014. The results relate to current practice in each country at the time, early 2015. The results were compiled and then verified with co-authors over the following months. RESULTS: Thirty-five completed surveys were received which describe a range of current practice for lung cancer data collection. Thirty countries have data collection at the national level, but this is not so in Albania, Bosnia-Herzegovina, Italy, Spain and Switzerland. Data collection varied from paper records with no survival analysis, to well-established electronic databases with links to census data and survival analyses. CONCLUSION: Using a network of committed clinicians, we have gathered validated comparative data reporting an observed difference in data collection mechanisms across Europe. We have identified the need to develop a well-designed dataset, whilst acknowledging what is feasible within each country, and aspiring to collect high quality data for clinical research.


Assuntos
Coleta de Dados/estatística & dados numéricos , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/terapia , Oncologia/estatística & dados numéricos , Coleta de Dados/métodos , Bases de Dados Factuais/estatística & dados numéricos , Europa (Continente) , Humanos , Oncologia/métodos
20.
Eur J Oncol Nurs ; 36: 103-111, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30322500

RESUMO

PURPOSE: Health services across the world utilise advanced practice in cancer care. In the UK, lung cancer nurse specialists (LCNS) are recognised as key components of quality care in national guidelines, yet access to LCNS contact is unequal and some responsibilities are reportedly left undone. We assess whether any variation in working practices of LCNS is attributable to factors of the lung cancer service at the hospital trust. METHOD: Nationwide workload analysis of LCNS working practices in England, linked at trust level to patient data from the National Lung Cancer Audit. Chi-squared tests were performed to assess whether patient contact, workload, involvement in multidisciplinary teams (MDT), and provision of key interventions were related to 1) the trust's lung cancer service size, 2) LCNS caseload, 3) anti-cancer treatment facilities and 4) lung cancer patient survival. RESULTS: Unpaid overtime was substantial for over 60% of nurses and not associated with particular service factors assessed; lack of administrative support was associated with large caseloads and chemotherapy facilities. LCNS at trusts with no specialty were more likely to challenge all MDT members (80%) compared with those at surgical (53%) or chemotherapy (58%) trusts. The most frequent specialist nursing intervention to not be routinely offered was proactive case management. CONCLUSION: Working practices of LCNS vary according to service factors, most frequently associated with trust anti-cancer treatment facilities. High workload pressures and limited ability to provide key interventions should be addressed across all services to ensure patients have access to recommended standards of care.


Assuntos
Administração de Caso/organização & administração , Acessibilidade aos Serviços de Saúde/organização & administração , Neoplasias Pulmonares/enfermagem , Enfermeiros Clínicos/organização & administração , Enfermagem Oncológica/organização & administração , Carga de Trabalho , Inglaterra , Humanos , Qualidade da Assistência à Saúde
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