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1.
Ann Entomol Soc Am ; 110(5): 449-456, 2017 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-29563645

RESUMO

Research-isolation is a common problem affecting many researchers who are disconnected from their research communities. It can be caused by a number of factors, including physical isolation, unfamiliar research topics, diversity, and the nature of the supervisory relationship. All of these aspects can have an impact on both work and the mental health of researchers. Increasingly, researchers are turning to social media for support, by both looking for communities and for increasing the impact of their work. In this paper, we set out a brief introduction to a range of social media platforms used by researchers and present a discussion of the networks within those platforms aimed at reducing research-isolation. These examples highlight just a few of the number of small communities that have grown online to meet the needs of those seeking support through social media. We conclude with some recommendations for those affected by research-isolation and highlight the need for more research into the role of social media on mental health in academics.

2.
Eur Radiol ; 25(5): 1247-56, 2015 May.
Artigo em Inglês | MEDLINE | ID: mdl-25749786

RESUMO

OBJECTIVES: The objectives are determine the optimal combination of MR parameters for discriminating tumour within the prostate using linear discriminant analysis (LDA) and to compare model accuracy with that of an experienced radiologist. METHODS: Multiparameter MRIs in 24 patients before prostatectomy were acquired. Tumour outlines from whole-mount histology, T2-defined peripheral zone (PZ), and central gland (CG) were superimposed onto slice-matched parametric maps. T2, Apparent Diffusion Coefficient, initial area under the gadolinium curve, vascular parameters (K(trans),Kep,Ve), and (choline+polyamines+creatine)/citrate were compared between tumour and non-tumour tissues. Receiver operating characteristic (ROC) curves determined sensitivity and specificity at spectroscopic voxel resolution and per lesion, and LDA determined the optimal multiparametric model for identifying tumours. Accuracy was compared with an expert observer. RESULTS: Tumours were significantly different from PZ and CG for all parameters (all p < 0.001). Area under the ROC curve for discriminating tumour from non-tumour was significantly greater (p < 0.001) for the multiparametric model than for individual parameters; at 90 % specificity, sensitivity was 41 % (MRSI voxel resolution) and 59 % per lesion. At this specificity, an expert observer achieved 28 % and 49 % sensitivity, respectively. CONCLUSION: The model was more accurate when parameters from all techniques were included and performed better than an expert observer evaluating these data. KEY POINTS: • The combined model increases diagnostic accuracy in prostate cancer compared with individual parameters • The optimal combined model includes parameters from diffusion, spectroscopy, perfusion, and anatominal MRI • The computed model improves tumour detection compared to an expert viewing parametric maps.


Assuntos
Meios de Contraste , Imageamento por Ressonância Magnética/métodos , Espectroscopia de Ressonância Magnética/métodos , Neoplasias da Próstata/patologia , Idoso , Imagem de Difusão por Ressonância Magnética/métodos , Humanos , Aumento da Imagem/métodos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Próstata/patologia , Curva ROC , Sensibilidade e Especificidade
3.
Br J Cancer ; 107(7): 1138-43, 2012 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-22918395

RESUMO

BACKGROUND: Locoregional recurrence is the major cause of treatment failure after surgery for oral squamous cell carcinoma. Molecular diagnostics have the potential to improve on clinicopathological parameters to predict this recurrence and plan adjuvant treatment. The test most frequently applied is based on detecting TP53 mutations, but alternative methodology is required for cases that harbour the wild-type gene. METHODS: One hundred and two cases with tumour-adjacent margins, considered to be clear margins by microscopy, were examined using carefully optimised molecular diagnostics based on detection of the TP53 and Ly-6D markers. The markers were also combined to provide a dual approach. RESULTS: The dual molecular diagnostic identified cases with a significant increase in the probablility of developing locoregional recurrence when tumour-adjacent positive and clear margins were compared (P=0.0001). These tests were most useful when the clearance at the resection margins was 5 mm or less. The TP53-based diagnostic was a better predictor of locoregional recurrence than established clinicopathological parameters. CONCLUSION: The optimised TP53-based diagnostic rapidly identifies an important subgroup of cases with close margins that will benefit from new treatment modalities to reduce the risk of recurrence.


Assuntos
Carcinoma de Células Escamosas/diagnóstico , Carcinoma de Células Escamosas/genética , Neoplasias de Cabeça e Pescoço/diagnóstico , Neoplasias de Cabeça e Pescoço/genética , Recidiva Local de Neoplasia/diagnóstico , Recidiva Local de Neoplasia/genética , Patologia Molecular/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/sangue , Biomarcadores Tumorais/genética , Carcinoma de Células Escamosas/sangue , Carcinoma de Células Escamosas/patologia , Feminino , Genes p53 , Neoplasias de Cabeça e Pescoço/sangue , Neoplasias de Cabeça e Pescoço/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Mutação , Recidiva Local de Neoplasia/sangue , Recidiva Local de Neoplasia/patologia , Estudos Prospectivos
4.
Strahlenther Onkol ; 188(10): 894-900, 2012 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-22933031

RESUMO

BACKGROUND: The goal of the current study was to investigate the tumor control probability (TCP) of advanced radiotherapy technologies for stage III non-small cell lung cancer (NSCLC) and to evaluate potential interplay effects between their applications. MATERIALS AND METHODS: Three-dimensional conformal radiotherapy (3D-CRT) with conventionally fractionated doses of 66 Gy served as reference for 13 patients with stage III NSCLC. Isotoxic dose escalation relative to the corresponding 3D-CRT plans was performed for three technologies and their combinations: intensity-modulated radiotherapy (IMRT), IMRT with a simultaneous integrated boost (IMRT-SIB) of 10% to the gross tumor volume (GTV), and adaptive re-planning twice during the treatment course (ART). All analyses were based on accumulated dose distributions using deformable image registration of CT images, which were acquired weekly during the treatment course. RESULTS: IMRT reduced the mean lung dose (MLD) by 5.6% ± 3.8% compared to 3D-CRT. ART resulted in lung sparing of 7.9% ± 4.8% and 9.2% ± 3.9% in 3D-CRT and IMRT planning, respectively. IMRT and ART escalated the irradiation dose by 6.6% ± 3.2% and 8.8% ± 6.3%, respectively, which was not statistically different. For the 7 patients with the largest GTVs, IMRT-SIB was superior to IMRT and ART with dose escalation of 11.9% ± 3.7%. The combination of ART, IMRT, and SIB achieved maximum dose escalation in all 13 patients by 17.1% ± 5.4% on average, which increased TCP from 19.9% ± 7.0 to 37.1% ± 10.1%. Adaptive re-planning was required to continuously conform the escalated and hypofractionated SIB doses to the shrinking tumor. CONCLUSION: Combining advanced radiotherapy technologies is considered as a safe and effective strategy to maximize local tumor control probability in stage III NSCLC.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/diagnóstico por imagem , Carcinoma Pulmonar de Células não Pequenas/radioterapia , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/radioterapia , Modelos Biológicos , Planejamento da Radioterapia Assistida por Computador/métodos , Adulto , Idoso , Carcinoma Pulmonar de Células não Pequenas/patologia , Terapia Combinada/métodos , Simulação por Computador , Relação Dose-Resposta à Radiação , Humanos , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Radiografia , Dosagem Radioterapêutica , Medição de Risco
5.
Clin Med (Lond) ; 12(2): 140-5, 2012 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-22586789

RESUMO

Patients referred to secondary care for specialist respiratory review frequently undergo multiple hospital attendances for investigations and consultations. This study evaluated the potential of a preclinic telephone consultation and subsequent coordination of tests and face-to-face consultations to reduce hospital visits. Total hospital attendances were recorded for three cohorts (participants, non-participants and comparators) for 6 months from first specialist contact. Patients completed the medical interview satisfaction scale-21 (MISS-21). The study showed that a preclinic telephone consultation can significantly reduce hospital visits over a fixed period without reducing patient satisfaction. In total, 20.8% of the participant group had three or more hospital attendances compared with 42.9% of the non-participant group (p = 0.001) and 44.7% of the comparator group (p = 0.002). Participants had fewer follow up visits and lower rates of non-attendance/late rearrangement of appointments. This service reduces unnecessary hospital visits, seems to improve patient compliance and may save costs associated with non-attendance and follow up consultations.


Assuntos
Serviços Centralizados no Hospital/métodos , Continuidade da Assistência ao Paciente , Encaminhamento e Consulta/organização & administração , Doenças Respiratórias , Telefone , Adulto , Idoso , Agendamento de Consultas , Continuidade da Assistência ao Paciente/economia , Continuidade da Assistência ao Paciente/organização & administração , Redução de Custos/métodos , Cuidado Periódico , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Ambulatório Hospitalar/organização & administração , Ambulatório Hospitalar/estatística & dados numéricos , Participação do Paciente , Satisfação do Paciente/estatística & dados numéricos , Encaminhamento e Consulta/normas , Doenças Respiratórias/diagnóstico , Doenças Respiratórias/terapia , Especialização , Inquéritos e Questionários
6.
Eur Respir J ; 37(2): 264-72, 2011 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-21115606

RESUMO

In between exacerbations, chronic obstructive pulmonary disease (COPD) is usually regarded as a stable condition, but there is increasing recognition of variability in this state. This cross-sectional study assessed patients' perception of symptom variability. Participants were outpatients > 45 yrs old with COPD, current or ex-smokers, forced expiratory volume in 1 s (FEV1) <50% predicted, FEV1/forced vital capacity < 0.7 and no exacerbation leading to therapeutic intervention in the previous 3 months. Patients' perceptions of COPD symptoms and their impact on daily life activities were recorded. Alterations in therapy use in response to COPD worsening were also recorded. COPD symptoms were experienced by 2,258 (92.5%) out of 2,441 patients during the 7 days before interview. Breathlessness was the most common symptom (72.5%). Daily and/or weekly symptom variability was reported by 62.7% of symptomatic patients; the morning was the worst time of day. Factors associated with perception of variability of breathlessness included younger age, symptom severity and recruitment to the study by general practitioners. The perception of variability was significantly different between European countries or regions. Patient-perceived COPD symptoms vary over the day and the week, and impact on daily activities; morning being the worst time of day. The majority of patients appear not to adjust treatment when symptoms worsen.


Assuntos
Doença Pulmonar Obstrutiva Crônica/epidemiologia , Fumar/epidemiologia , Atividades Cotidianas , Corticosteroides/uso terapêutico , Idoso , Broncodilatadores/uso terapêutico , Estudos Transversais , Dispneia/tratamento farmacológico , Dispneia/epidemiologia , Europa (Continente)/epidemiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Medicamentos para o Sistema Respiratório/uso terapêutico , Índice de Gravidade de Doença
7.
Oral Dis ; 17 Suppl 1: 7-22, 2011 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-21382136

RESUMO

Squamous cell carcinoma (SCC) of the oral and oropharyngeal region is the sixth most common malignancy in the world today. Despite numerous advances in treatment, long-term survival from this disease remains poor. Early detection can decrease both morbidity and mortality associated with this neoplasm. However, screening for potentially malignant disease is typically confounded by difficulty in discriminating between reactive/inflammatory lesions vs those lesions that are premalignant in nature. Furthermore, the histologic diagnosis of dysplasia can be subjective and is thus prone to a considerable range of interpretation. Similarly, no definitive, validated criteria exist for predicting which dysplastic lesions are most likely to progress to cancer over time. Given this state of science, the presence of dysplasia can only be used to indicate that an oral lesion may have an increased risk of malignant transformation. Molecular biomarkers capable of identifying the subset of lesions likely to progress to cancer are required to eliminate this clinical diagnostic dilemma. The purpose of this review is to assess the current state of knowledge regarding genetic/epigenetic alterations observed in oral mucosal premalignancy. In addition, recommendations for future research studies directed at defining the predictive capacity of specific biomarkers in this modeling are presented.


Assuntos
Epigênese Genética/genética , Neoplasias Bucais/genética , Lesões Pré-Cancerosas/genética , Biomarcadores Tumorais/genética , Carcinoma de Células Escamosas/genética , Transformação Celular Neoplásica/genética , Pesquisa em Odontologia/tendências , Epigenômica/tendências , Previsões , Humanos
8.
Chron Respir Dis ; 8(1): 31-40, 2011.
Artigo em Inglês | MEDLINE | ID: mdl-21339372

RESUMO

Personalised written action plans are increasingly regarded as an important component of chronic obstructive pulmonary disease (COPD) self-management support and yet they may not be understood by those with limited literacy skills. This study was designed to produce a comprehensible pictorial COPD action plan for use by patients and health care professionals. With advice from a group of doctors and nurses a 'standard' written COPD action plan was translated by a medical artist into a series of pictorial images. These were assessed using the techniques of guessability and translucency in 21 adults attending a COPD clinic in a London hospital. Guessability and translucency scores show that pictograms were reasonably well understood, with only 3 pictograms showing low score in both guessability and translucency questionnaires. These included images depicting increased sputum production, swollen ankles, and use of extra doses of reliever medication. However, after brief spoken reinforcement about self-management, most patients could use the pictorial plan to suggest appropriate self-management behaviour such as when to access medical care. We have developed a pictorial COPD action plan. Pictorial methods represent an effective method of reinforcing the spoken word for all ranges of literacy.


Assuntos
Participação da Comunidade/métodos , Gráficos por Computador , Planejamento de Assistência ao Paciente , Doença Pulmonar Obstrutiva Crônica/terapia , Autocuidado/métodos , Idoso , Feminino , Letramento em Saúde/métodos , Humanos , Masculino , Pessoa de Meia-Idade , Educação de Pacientes como Assunto/métodos
9.
AAPS J ; 23(2): 34, 2021 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-33649990

RESUMO

In May 2020, the EU Reference Laboratory for alternatives to animal testing (EURL ECVAM) published a recommendation report entitled "Recommendation on nonanimal-derived antibodies". In this report, the EURL ECVAM specifically states: "Therefore, taking into consideration the ESAC Opinion on the scientific validity of replacements for animal-derived antibodies, EURL ECVAM recommends that animals should no longer be used for the development and production of antibodies for research, regulatory, diagnostic and therapeutic applications. The provisions of Directive 2010/63/EU should be respected, and EU countries should no longer authorise the development and production of antibodies through animal immunisation, where robust, legitimate scientific justification is lacking." (1). Here, we are providing the American Association of Pharmaceutical Scientists (AAPS) opinion on the EURL ECVAM recommendation report. In brief, there has been a clear and strong progress in reduction of animal use in the drug discovery and development process, including significant reduction of animal use in production of antibody reagents. Yet, it is proposed that more data need to be generated, shared and discussed within the scientific community before a decision to implement the change to non-animal derived antibodies is made.


Assuntos
Alternativas ao Uso de Animais/normas , Anticorpos Monoclonais/isolamento & purificação , Farmácia/normas , Sociedades Farmacêuticas/normas , Tecnologia Farmacêutica/normas , Animais , Anticorpos Monoclonais/genética , Anticorpos Monoclonais/uso terapêutico , União Europeia , Políticas , Proteínas Recombinantes/genética , Proteínas Recombinantes/isolamento & purificação , Proteínas Recombinantes/uso terapêutico , Tecnologia Farmacêutica/métodos , Estados Unidos
10.
Eur Respir J ; 36(1): 96-104, 2010 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-19897551

RESUMO

This report concerns the development and validation of two patient-reported outcomes questionnaires developed to assess chronic obstructive pulmonary disease (COPD) patients' ability to perform morning activities and to evaluate their morning symptoms. Based on interviews with COPD patients, the Capacity of Daily Living during the Morning (CDLM) questionnaire and the Global Chest Symptoms Questionnaire (GCSQ) were developed, linguistically validated and incorporated into two multicentre, randomised trials involving a total of 1,100 COPD patients; those trials were registered at ClinicalTrials.gov (NCT00496470 and NCT00542880). Data from these trials were used to determine the reliability, validity and responsiveness of the questionnaires and to derive estimates of minimal important differences (MIDs). Both questionnaires displayed good-to-high reliability (Cronbach's alpha 0.75-0.93). Analysis of convergent validity showed that CDLM and GCSQ scores correlated significantly (p<0.001) with symptoms, health-related quality of life (HRQoL) and use of rescue medication. In both trials, CDLM and GCSQ scores discriminated between patients with different levels of HRQoL, as assessed by the St George's Respiratory Questionnaire for COPD patients (SGRQ-C), but not with disease severity, as assessed by the Global Initiative for Chronic Obstructive Lung Disease (GOLD) criteria. A significant improvement in CDLM and GCSQ scores occurred in response to treatment. Estimations of MID scores, corresponding to an SGRQ-C MID of 4, were 0.20 for the CDLM questionnaire and 0.15 for the GCSQ. Both the CDLM questionnaire and the GCSQ are easy-to-use, reliable, responsive, self-administered questionnaires that report on patients' symptoms and ability to perform morning activities.


Assuntos
Atividades Cotidianas , Doença Pulmonar Obstrutiva Crônica/fisiopatologia , Doença Pulmonar Obstrutiva Crônica/psicologia , Qualidade de Vida/psicologia , Inquéritos e Questionários , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Reprodutibilidade dos Testes , Índice de Gravidade de Doença , Resultado do Tratamento
11.
Med Phys ; 37(4): 1768-77, 2010 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-20443499

RESUMO

PURPOSE: Modern radiotherapy treatments can be optimized using dose-volume constraints which specify the volume of tumor and organs-at-risk receiving a given threshold dose. Careful derivation and evaluation of rectal constraints is essential to allow safe dose escalation in radiotherapy of prostate cancer. The authors present a new type of hybrid dosimetric constraint which comprises both volumetric and spatial factors of the dose-distribution. The authors also propose a framework to evaluate these constraints. METHODS: The authors used data from the RT01 prostate radiotherapy trial (ISRCTN 47772397) to derive this set of hybrid constraints for the rectum based on measures extracted from dose-surface maps. For comparison, the authors also derive a set of dose-volume constraints. In order to evaluate these dosimetric constraints, the authors propose a new framework for predicting radiation-induced toxicities using Bayesian logistic regression with high-order interactions. The predictive power of the new RT01-based constraints, as well as of two sets of rectal dose-volume constraints proposed in the recent literature-The constraints proposed by other researchers [C. Fiorino, G. Fellin, T. Rancati, V. Vavassori, C. Bianchi, V. C. Borca, G. Girelli, M. Mapelli, L. Menegotti, S. Nava, and R. Valdagni, "Clinical and dosimetric predictors of late rectal syndrome after 3D-CRT for localized prostate cancer: Preliminary results of a multicenter prospective study," Int. J. Radiat. Oncol., Biol., Phys. 70, 1130-1137 (2008)] and the constraints used in the conventional or hypofractionated high dose intensity modulated radiotherapy for prostate cancer (CHHiP) trial [C. P. South, V. S. Khoo, O. Naismith, A. Norman, and D. P. Dearnaley, "A comparison of treatment planning techniques used in two randomised UK external beam radiotherapy trials for localised prostate cancer," Clin. Oncol. (R Coll. Radiol) 20, 15-21 (2008)]--were evaluated using a tenfold cross-validation with follow-up data from the RT01 trial. The predictive power was quantified using receiver-operator characteristic (ROC) curves. Toxicities considered were rectal bleeding, loose stools, and a global toxicity score. RESULTS: Dose-volume constraints had less predictive power than the new type of hybrid constraints. A probabilistic model for predicting rectal bleeding based on the dose-volume constraints proposed by other researchers [C. Fiorino, G. Fellin, T. Rancati, V. Vavassori, C. Bianchi, V. C. Borca, G. Girelli, M. Mapelli, L. Menegotti, S. Nava, and R. Valdagni, "Clinical and dosimetric predictors of late rectal syndrome after 3D-CRT for localized prostate cancer: Preliminary results of a multicenter prospective study," Int. J. Radiat. Oncol., Biol., Phys. 70, 1130-1137 (2008)], the CHHiP dose-volume constraints, the RT01-based dose-volume constraints, and the hybrid constraints resulted in average areas under the ROC curves of 0.56, 0.58, 0.62, and 0.67, respectively. For predicting loose stools, the corresponding values were 0.57, 0.53, 0.66, and 0.71, respectively. The areas under the respective ROC curves for predicting the global toxicity score were 0.58, 0.55, 0.61, and 0.63. CONCLUSIONS: Thus, imposing the new type of hybrid constraints when generating a treatment plan should result in a reduction in the incidence of radiation-induced late rectal toxicity.


Assuntos
Neoplasias da Próstata/radioterapia , Radiometria/métodos , Planejamento da Radioterapia Assistida por Computador/métodos , Radioterapia/métodos , Área Sob a Curva , Teorema de Bayes , Estudos de Coortes , Fracionamento da Dose de Radiação , Relação Dose-Resposta à Radiação , Reações Falso-Positivas , Humanos , Masculino , Curva ROC , Reto/efeitos da radiação , Análise de Regressão
12.
Med Phys ; 37(2): 516-31, 2010 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-20229860

RESUMO

PURPOSE: There is significant current interest in the use of biological image guidance in radiotherapy planning. In lung-cancer treatment, tumor motion due to respiration is known to be a limitation. This is particularly true in PET, where image data are collected over a number of minutes. An in-house-developed 4D PET acquisition mode is described and an analysis of the effects of acquisition parameters on the reconstructed image quality is presented. The potential impact of the resulting biological image quality on radiotherapy planning is then quantified in terms of tumor control probability (TCP). METHODS: Data were acquired using a human torso phantom comprised of a hot '8F-filled spheroidal "tumor" (40 mm in diameter) suspended in an air-filled "lung" cylinder and surrounded by a warm 18F-filled background. Two different sphere-to-background (S/B) ratios were used. The tumor was connected to a 3-axis computer-controlled motion stage and could be moved during PET data acquisition. Images were acquired with a range of count statistics, motion blurring, and CT attenuation correction (CTAC) misalignment. Four simple models were proposed for the assignment of clonogenic cell density according to the voxel value. The impact of image artifacts was then assessed by calculating the TCP, which is the probability that no clonogenic tumor cell remains after a given dose of radiation. TCP was calculated for a uniform dose distribution in the tumor. RESULTS: Reduced count statistics and misaligned CTAC images had the most detrimental impact on the image fidelity. It was found that in both cases the images became less intense, demonstrated by smaller number of voxels at the maximum values. The maximum TCP difference between images with the least and most noise was 3.4% (S/B=3), and with weakest and strongest CT misalignment artifacts, it was 3.2% (S/B = 10). Motion blurring only contributed weakly to the TCP imprecision at 1.7% (S/B=10) between best- and worst-case images. However, the model-calculated TCP showed increasing differences from the ground truth as the complexity of the model increased [maximum difference of approximately 8% (model 3)], which could be attributed to the partial volume effect. CONCLUSIONS: Based on the results of this study, it is believed that simple techniques of biologically guided radiotherapy planning for lung cancer should be feasible at intermediate contrast levels (tumor-to-background ratio of approximately 10) with the clinically achievable image quality.


Assuntos
Fluordesoxiglucose F18 , Interpretação de Imagem Assistida por Computador/métodos , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/radioterapia , Tomografia por Emissão de Pósitrons/métodos , Planejamento da Radioterapia Assistida por Computador/métodos , Radioterapia Assistida por Computador/métodos , Determinação de Ponto Final , Humanos , Compostos Radiofarmacêuticos , Dosagem Radioterapêutica , Reprodutibilidade dos Testes , Sensibilidade e Especificidade
13.
Br J Cancer ; 101(3): 418-23, 2009 Aug 04.
Artigo em Inglês | MEDLINE | ID: mdl-19623179

RESUMO

BACKGROUND: Tumour cells may persist at the operative site after seemingly adequate surgery. Radiotherapy is often given in an attempt to prevent repopulation, but this modality cannot be relied upon to prevent locoregional recurrence. An alternative strategy is to take advantage of the requirement of tumour cells to develop an independent blood supply and block this process to prevent recurrence. METHODS: In this study, we evaluate the effect of the angiogenesis inhibitor, ZD4190, using a rodent model of residual carcinoma in deep tissues, mimicking the clinical scenario where low numbers of malignant cells persist at the operative site. RESULTS: The tumour burden that could be eliminated was dependent on the site where the cells were implanted. Immediate treatment with ZD4190 prevented outgrowth of up to 2.5 x 10(5) cells in the rectus muscle and 1 x 10(5) in the gastrocnemius, whereas control animals developed large tumours. When more than 2.5 x 10(6) cells were implanted into the rectus or 1 x 10(6) into the gastrocnemius and treatment was maintained for 3 weeks, the carcinomas that developed in ZD4190-treated animals showed a reduced microvessel density and increased necrosis when compared with the vehicle-treated controls, but an infiltrative growth pattern was common. CONCLUSION: These findings suggest that antiangiogenic agents have a role to play in preventing outgrowth of residual carcinoma and are likely to be most effective when the tumour burden is minimal.


Assuntos
Inibidores da Angiogênese/uso terapêutico , Neoplasia Residual/tratamento farmacológico , Neoplasias Experimentais/tratamento farmacológico , Quinazolinas/uso terapêutico , Triazóis/uso terapêutico , Animais , Modelos Animais de Doenças , Feminino , Camundongos , Camundongos Endogâmicos C57BL , Neoplasia Residual/irrigação sanguínea , Neoplasia Residual/patologia , Neoplasias Experimentais/irrigação sanguínea , Neoplasias Experimentais/patologia , Fator A de Crescimento do Endotélio Vascular/análise , Receptor 2 de Fatores de Crescimento do Endotélio Vascular/análise
14.
Med Phys ; 36(10): 4379-88, 2009 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-19928068

RESUMO

The technical feasibility and potential benefits of voxel-based nonuniform dose prescriptions for biologically heterogeneous tumors have been widely demonstrated. In some cases, an "ideal" dose prescription has been generated by individualizing the dose to every voxel within the target, but often this voxel-based prescription has been discretized into a small number of compartments. The number of dose levels utilized and the methods used for prescribing doses and assigning tumor voxels to different dose compartments have varied significantly. The authors present an investigation into the relationship between the complexity of the dose prescription and the tumor control probability (TCP) for a number of these methods. The linear quadratic model of cell killing was used in conjunction with a number of modeled tumors heterogeneous in clonogen density, oxygenation, or proliferation. Models based on simple mathematical functions, published biological data, and biological image data were investigated. Target voxels were assigned to dose compartments using (i) simple rules based on the initial biological distribution, (ii) iterative methods designed to maximize the achievable TCP, or (iii) methods based on an ideal dose prescription. The relative performance of the simple rules was found to depend on the form of heterogeneity of the tumor, while the iterative and ideal dose methods performed comparably for all models investigated. In all cases the maximum achievable TCP was approached within the first few (typically two to five) compartments. Results suggest that irrespective of the pattern of heterogeneity, the optimal dose prescription can be well approximated using only a few dose levels but only if both the compartment boundaries and prescribed dose levels are well chosen.


Assuntos
Fracionamento da Dose de Radiação , Modelos Biológicos , Neoplasias/fisiopatologia , Neoplasias/radioterapia , Planejamento da Radioterapia Assistida por Computador/métodos , Radioterapia Assistida por Computador/métodos , Radioterapia Conformacional/métodos , Simulação por Computador , Humanos , Modelos Estatísticos , Dosagem Radioterapêutica
15.
Phys Med Biol ; 54(11): 3563-78, 2009 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-19454782

RESUMO

A target-tracking, intensity-modulated delivery on an Elekta MLCi system was assessed by film measurement with a simulated target-motion trajectory. A toroidally shaped idealized target surrounding an organ at risk necessitating multiple field segments to irradiate the target and spare the organ at risk was defined in a solid-water phantom. The phantom was programmed to move following a reproducible 2D elliptical trajectory in the beam's-eye view with a period of 10 s. Static and target-tracking treatments were planned for delivery on a standard Elekta Precise series linac with integrated MLCi system. Dose was delivered in three ways: (i) a static treatment to a static phantom, (ii) a static treatment to a moving phantom and (iii) a target-tracking treatment to a moving phantom. The dose delivered was assessed by film measurement on the central plane through the target and organ at risk. The target dose blurring was quantified by the standard deviation of the dose to the target which was evaluated as 2.8% for the static treatment to the static phantom, 7.2% for the static treatment to the moving phantom and 2.6% for the tracking treatment to the moving phantom. The mean organ-at-risk dose was 38.2%, 54.0% and 38.2% of the prescription dose for each delivery case. We have therefore shown that the linac is capable of delivering target-tracking fields with MLCs for the target trajectories tested.


Assuntos
Radioterapia Assistida por Computador/métodos , Estudos de Viabilidade , Movimento (Física) , Imagens de Fantasmas , Dosagem Radioterapêutica , Risco , Fatores de Tempo , Gravação em Vídeo
16.
J Asthma ; 46(8): 767-72, 2009 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-19863278

RESUMO

BACKGROUND: There is no comprehensive information available concerning the way in which care is provided for those with allergic conditions in Europe. OBJECTIVE: To determine who cares for those with asthma, allergic dermatitis, and rhinitis in Europe and to determine the involvement of primary care and other healthcare professionals and the use of patient education and guidelines. METHODS: A questionnaire survey of colleagues in 43 institutions in 33 European countries with results being related to published sources of information regarding prevalence of allergic diseases in different countries and published data regarding availability of doctors and expenditure on healthcare. RESULTS: A total of 33 of 43 institutions completed the survey (76.7%) with information being obtained from 26 of the 33 countries surveyed (78.7%). There are wide differences in the use of different healthcare professionals in different countries, with those for asthma, for example, being most likely to be cared for by an allergologist in some countries and by a primary care physician in many others. There was much greater awareness of guidelines for asthma and little reported usage of guidelines in the management of those with allergic skin diseases, and while self-management education was offered most to those with asthma, there was a wide variation in the usage of group education. CONCLUSIONS: Many of the differences revealed by this survey cannot be explained by the availability of different healthcare professionals nor by differences in healthcare expenditure, and such differences need further evaluation to determine their effect on outcomes and the economics of healthcare so that we may determine that which is optimal.


Assuntos
Asma/terapia , Dermatite Alérgica de Contato/terapia , Rinite/terapia , Alergia e Imunologia , Europa (Continente) , Guias como Assunto , Pessoal de Saúde , Humanos , Educação de Pacientes como Assunto , Inquéritos e Questionários
17.
Thorax ; 63(3): 194-200, 2008 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-17901162

RESUMO

OBJECTIVES: To determine the effects of a nurse led intermediate care programme in patients who have been hospitalised with an acute exacerbation of chronic obstructive pulmonary disease (AECOPD). DESIGN: Randomised controlled trial. SETTING: Community and hospital care in west London. PARTICIPANTS: 122 patients with COPD. INTERVENTION: A care package incorporating initial pulmonary rehabilitation and self-management education, provision of a written, personalised COPD action plan, monthly telephone calls and 3 monthly home visits by a specialist nurse for a period of 2 years. MAIN OUTCOME MEASURE: Hospital readmission rate. SECONDARY OUTCOMES: Unscheduled primary care consultations and quality of life. RESULTS: There were no differences in hospital admission rates or in exacerbation rates between the two groups. Self-management of exacerbations was significantly different and the intervention group were more likely to be treated with oral steroids alone or oral steroids and antibiotics, and the initiators of treatment for exacerbations were statistically more likely to be the patients themselves. 12 patients in the control group died during the 2 year period, eight as a result of COPD, compared with six patients in the intervention group, of whom one died from COPD. This is a significant difference. When the numbers were adjusted to reflect the numbers still alive at 2 years, in the intervention group patients reported a total of 171 unscheduled contacts with their general practitioner (GP) and in the control group, 280 contacts. The number needed to treat was 0.558--ie, for every one COPD patient receiving the intervention and self-management advice, there were 1.79 fewer unscheduled contacts with the GP. CONCLUSIONS: An intermediate care package incorporating pulmonary rehabilitation, self-management education and the receipt of a written COPD action plan, together with regular nurse contact, is associated with a reduced need for unscheduled primary care consultations and a reduction in deaths due to COPD but did not affect the hospital readmission rate.


Assuntos
Doença Pulmonar Obstrutiva Crônica/enfermagem , Doença Aguda , Idoso , Serviços de Saúde Comunitária/economia , Serviços de Saúde Comunitária/métodos , Feminino , Custos de Cuidados de Saúde , Hospitalização/estatística & dados numéricos , Humanos , Masculino , Educação de Pacientes como Assunto , Doença Pulmonar Obstrutiva Crônica/economia , Doença Pulmonar Obstrutiva Crônica/fisiopatologia , Qualidade de Vida , Espirometria , Esteroides/uso terapêutico , Comprimidos , Resultado do Tratamento
18.
Thorax ; 63(9): 778-83, 2008 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-18281394

RESUMO

OBJECTIVES: To determine whether well trained lay people could deliver asthma self-management education with comparable outcomes to that achieved by primary care based practice nurses. DESIGN: Randomised equivalence trial. SETTING: 39 general practices in West London and North West England. PARTICIPANTS: 567 patients with asthma who were on regular maintenance therapy. 15 lay educators were recruited and trained to deliver asthma self-management education. INTERVENTION: An initial consultation of up to 45 min offered either by a lay educator or a practice based primary care nurse, followed by a second shorter face to face consultation and telephone follow-up for 1 year. MAIN OUTCOME MEASURES: Unscheduled need for healthcare. SECONDARY OUTCOME MEASURES: Patient satisfaction and need for courses of oral steroids. RESULTS: 567 patients were randomised to care by a nurse (n = 287) or a lay educator (n = 280) and 146 and 171, respectively, attended the first face to face educational session. During the first two consultations, management changes were made in 35/146 patients seen by a practice nurse (24.0%) and in 56/171 patients (32.7%) seen by a lay educator. For 418/567 patients (73.7%), we have 1 year data on use of unscheduled healthcare. Under an intention to treat approach, 61/205 patients (29.8%) in the nurse led group required unscheduled care compared with 65/213 (30.5%) in the lay led group (90% CI for difference -8.1% to 6.6%; 95% CI for difference -9.5% to 8.0%). The 90% CI contained the predetermined equivalence region (-5% to +5%) giving an inconclusive result regarding the equivalence of the two approaches. Despite the fact that all patients had been prescribed regular maintenance therapy, 122/418 patients (29.2%) required courses of steroid tablets during the course of 1 year. Patient satisfaction following the initial face to face consultation was similar in both groups. CONCLUSIONS: It is possible to recruit and train lay educators to deliver a discrete area of respiratory care, with comparable outcomes to those seen by nurses.


Assuntos
Asma/enfermagem , Medicina de Família e Comunidade/normas , Assistência Domiciliar/educação , Profissionais de Enfermagem/normas , Educação de Pacientes como Assunto/normas , Autocuidado/normas , Adolescente , Adulto , Idoso , Inglaterra , Medicina de Família e Comunidade/estatística & dados numéricos , Feminino , Hospitalização/estatística & dados numéricos , Humanos , Masculino , Pessoa de Meia-Idade , Aceitação pelo Paciente de Cuidados de Saúde/estatística & dados numéricos
19.
Eur Respir J ; 32(3): 545-54, 2008 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-18757695

RESUMO

Concepts of asthma severity and control are important in the evaluation of patients and their response to treatment but the terminology is not standardised and the terms are often used interchangeably. This review, arising from the work of an American Thoracic Society/European Respiratory Society Task Force, identifies the need for separate concepts of control and severity, describes their evolution in asthma guidelines and provides a framework for understanding the relationship between current concepts of asthma phenotype, severity and control. "Asthma control" refers to the extent to which the manifestations of asthma have been reduced or removed by treatment. Its assessment should incorporate the dual components of current clinical control (e.g. symptoms, reliever use and lung function) and future risk (e.g. exacerbations and lung function decline). The most clinically useful concept of asthma severity is based on the intensity of treatment required to achieve good asthma control, i.e. severity is assessed during treatment. Severe asthma is defined as the requirement for (not necessarily just prescription or use of) high-intensity treatment. Asthma severity may be influenced by the underlying disease activity and by the patient's phenotype, both of which may be further described using pathological and physiological markers. These markers can also act as surrogate measures for future risk.


Assuntos
Antiasmáticos/uso terapêutico , Asma/tratamento farmacológico , Asma/fisiopatologia , Guias de Prática Clínica como Assunto , Ensaios Clínicos como Assunto , Resistência a Medicamentos , Humanos , Testes de Função Respiratória
20.
Med Phys ; 35(10): 4599-611, 2008 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-18975706

RESUMO

We present a formalism for using functional imaging both to derive patient-specific radiobiological properties and consequently to prescribe optimal nonuniform radiotherapy dose distributions. The ability to quantitatively assess the response to an initial course of radiotherapy would allow the derivation of radiobiological parameters for individual patients. Both an iterative optimization and an analytical approach to this problem were investigated and illustrated by application to the linear-quadratic model of cell killing using simulated parametric data for a modeled tumor. Potential gains in local control were assessed by comparing uniform dose distributions with optimized dose distributions of equal integral dose. The effect on local prescribed dose of variations in effective radiosensitivity, tumor burden, and proliferation rate was investigated, with results suggesting that dose variations would be significant but clinically achievable. The sensitivity of derived parameters to image noise and the effect of varying the initial fractionation and imaging schedule were assessed. The analytical approach proved remarkably robust, with 10% image noise resulting in dose errors of approximately 1% for a clinically relevant set of parameters. Potential benefits were demonstrated by using this formalism to prescribe nonuniform dose distributions for model tumors using a range of literature-derived parameters. The redistribution of dose improved tumor control probability by factors between 1.03 and 4.27 for a range of model tumors.


Assuntos
Algoritmos , Modelos Biológicos , Neoplasias/radioterapia , Radiometria/métodos , Planejamento da Radioterapia Assistida por Computador/métodos , Simulação por Computador , Humanos , Dosagem Radioterapêutica
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