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1.
Clin Oncol (R Coll Radiol) ; 36(7): e197-e208, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38631978

RESUMO

AIMS: The objective of this study was to develop a two-year overall survival model for inoperable stage I-III non-small cell lung cancer (NSCLC) patients using routine radiation oncology data over a federated (distributed) learning network and evaluate the potential of decision support for curative versus palliative radiotherapy. METHODS: A federated infrastructure of data extraction, de-identification, standardisation, image analysis, and modelling was installed for seven clinics to obtain clinical and imaging features and survival information for patients treated in 2011-2019. A logistic regression model was trained for the 2011-2016 curative patient cohort and validated for the 2017-2019 cohort. Features were selected with univariate and model-based analysis and optimised using bootstrapping. System performance was assessed by the receiver operating characteristic (ROC) and corresponding area under curve (AUC), C-index, calibration metrics and Kaplan-Meier survival curves, with risk groups defined by model probability quartiles. Decision support was evaluated using a case-control analysis using propensity matching between treatment groups. RESULTS: 1655 patient datasets were included. The overall model AUC was 0.68. Fifty-eight percent of patients treated with palliative radiotherapy had a low-to-moderate risk prediction according to the model, with survival times not significantly different (p = 0.87 and 0.061) from patients treated with curative radiotherapy classified as high-risk by the model. When survival was simulated by risk group and model-indicated treatment, there was an estimated 11% increase in survival rate at two years (p < 0.01). CONCLUSION: Federated learning over multiple institution data can be used to develop and validate decision support systems for lung cancer while quantifying the potential impact of their use in practice. This paves the way for personalised medicine, where decisions can be based more closely on individual patient details from routine care.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Humanos , Carcinoma Pulmonar de Células não Pequenas/radioterapia , Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Neoplasias Pulmonares/radioterapia , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/mortalidade , Feminino , Masculino , Idoso , Pessoa de Meia-Idade , Sistemas de Apoio a Decisões Clínicas , Idoso de 80 Anos ou mais , Técnicas de Apoio para a Decisão
3.
Hum Reprod ; 35(4): 770-784, 2020 04 28.
Artigo em Inglês | MEDLINE | ID: mdl-32240301

RESUMO

STUDY QUESTION: Can an artificial intelligence (AI)-based model predict human embryo viability using images captured by optical light microscopy? SUMMARY ANSWER: We have combined computer vision image processing methods and deep learning techniques to create the non-invasive Life Whisperer AI model for robust prediction of embryo viability, as measured by clinical pregnancy outcome, using single static images of Day 5 blastocysts obtained from standard optical light microscope systems. WHAT IS KNOWN ALREADY: Embryo selection following IVF is a critical factor in determining the success of ensuing pregnancy. Traditional morphokinetic grading by trained embryologists can be subjective and variable, and other complementary techniques, such as time-lapse imaging, require costly equipment and have not reliably demonstrated predictive ability for the endpoint of clinical pregnancy. AI methods are being investigated as a promising means for improving embryo selection and predicting implantation and pregnancy outcomes. STUDY DESIGN, SIZE, DURATION: These studies involved analysis of retrospectively collected data including standard optical light microscope images and clinical outcomes of 8886 embryos from 11 different IVF clinics, across three different countries, between 2011 and 2018. PARTICIPANTS/MATERIALS, SETTING, METHODS: The AI-based model was trained using static two-dimensional optical light microscope images with known clinical pregnancy outcome as measured by fetal heartbeat to provide a confidence score for prediction of pregnancy. Predictive accuracy was determined by evaluating sensitivity, specificity and overall weighted accuracy, and was visualized using histograms of the distributions of predictions. Comparison to embryologists' predictive accuracy was performed using a binary classification approach and a 5-band ranking comparison. MAIN RESULTS AND THE ROLE OF CHANCE: The Life Whisperer AI model showed a sensitivity of 70.1% for viable embryos while maintaining a specificity of 60.5% for non-viable embryos across three independent blind test sets from different clinics. The weighted overall accuracy in each blind test set was >63%, with a combined accuracy of 64.3% across both viable and non-viable embryos, demonstrating model robustness and generalizability beyond the result expected from chance. Distributions of predictions showed clear separation of correctly and incorrectly classified embryos. Binary comparison of viable/non-viable embryo classification demonstrated an improvement of 24.7% over embryologists' accuracy (P = 0.047, n = 2, Student's t test), and 5-band ranking comparison demonstrated an improvement of 42.0% over embryologists (P = 0.028, n = 2, Student's t test). LIMITATIONS, REASONS FOR CAUTION: The AI model developed here is limited to analysis of Day 5 embryos; therefore, further evaluation or modification of the model is needed to incorporate information from different time points. The endpoint described is clinical pregnancy as measured by fetal heartbeat, and this does not indicate the probability of live birth. The current investigation was performed with retrospectively collected data, and hence it will be of importance to collect data prospectively to assess real-world use of the AI model. WIDER IMPLICATIONS OF THE FINDINGS: These studies demonstrated an improved predictive ability for evaluation of embryo viability when compared with embryologists' traditional morphokinetic grading methods. The superior accuracy of the Life Whisperer AI model could lead to improved pregnancy success rates in IVF when used in a clinical setting. It could also potentially assist in standardization of embryo selection methods across multiple clinical environments, while eliminating the need for complex time-lapse imaging equipment. Finally, the cloud-based software application used to apply the Life Whisperer AI model in clinical practice makes it broadly applicable and globally scalable to IVF clinics worldwide. STUDY FUNDING/COMPETING INTEREST(S): Life Whisperer Diagnostics, Pty Ltd is a wholly owned subsidiary of the parent company, Presagen Pty Ltd. Funding for the study was provided by Presagen with grant funding received from the South Australian Government: Research, Commercialisation and Startup Fund (RCSF). 'In kind' support and embryology expertise to guide algorithm development were provided by Ovation Fertility. J.M.M.H., D.P. and M.P. are co-owners of Life Whisperer and Presagen. Presagen has filed a provisional patent for the technology described in this manuscript (52985P pending). A.P.M. owns stock in Life Whisperer, and S.M.D., A.J., T.N. and A.P.M. are employees of Life Whisperer.


Assuntos
Inteligência Artificial , Microscopia , Austrália , Feminino , Fertilização in vitro , Humanos , Gravidez , Estudos Retrospectivos
4.
J Head Trauma Rehabil ; 35(2): 127-139, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31033744

RESUMO

OBJECTIVE: To describe trajectories of functioning up to 5 years after traumatic brain injury (TBI) that required inpatient rehabilitation in the United States using individual growth curve models conditioned on factors associated with variability in functioning and independence over time. DESIGN: Secondary analysis of population-weighted data from a multicenter longitudinal cohort study. SETTING: Acute inpatient rehabilitation facilities. PARTICIPANTS: A total of 4624 individuals 16 years and older with a primary diagnosis of TBI. MAIN OUTCOME MEASURES: Ratings of global disability and supervision needs as reported by participants or proxy during follow-up telephone interviews at 1, 2, and 5 years postinjury. RESULTS: Many TBI survivors experience functional improvement through 1 and 2 years postinjury, followed by a decline in functioning and decreased independence by 5 years. However, there was considerable heterogeneity in outcomes across individuals. Factors such as older age, non-White race, lower preinjury productivity, public payer source, longer length of inpatient rehabilitation stay, and lower discharge functional status were found to negatively impact trajectories of change over time. CONCLUSIONS: These findings can inform the content, timing, and target recipients of interventions designed to maximize functional independence after TBI.


Assuntos
Lesões Encefálicas Traumáticas , Adulto , Idoso , Lesões Encefálicas Traumáticas/diagnóstico , Lesões Encefálicas Traumáticas/reabilitação , Centers for Disease Control and Prevention, U.S. , Feminino , Humanos , Pacientes Internados , Estudos Longitudinais , Masculino , Medicare , Desempenho Físico Funcional , Estados Unidos
5.
Diabet Med ; 2018 Jun 08.
Artigo em Inglês | MEDLINE | ID: mdl-29882990

RESUMO

AIM: To explore reasons for the poor uptake of accredited diabetes self-management education (DSME) in adults with Type 1 diabetes. METHODS: The study was set in an urban population in South London, UK. A cross sectional survey gathered demographic, diabetes service-use data, psychological scores and reasons for non-attendance at locally-available DSME. In addition, 56 healthcare professionals were surveyed. RESULTS: Responses to surveys were returned by 496 adults with Type 1 diabetes (33% response rate), of whom 263 had attended DSME (53%). Multivariable analysis adjusted for significant variables identified four key variables influencing attendance. Non-attendance was associated with men (OR 0.55 CI 0.37-0.84, p = 0.005), lower educational attainment (OR 0.45 CI 0.28-0.73, p = 0.001), higher glycated haemoglobin (OR 1.74 CI 1.03-2.94, p = 0.04) and healthcare professional encouragement to attend (OR 1.7 CI 1.28-2.3, p = 0.001). The most frequently reported barriers to attendance were work (37%) and time (14%) commitments. Only 49% of healthcare professionals (HCPs) correctly identified the most likely barriers. Those HCPs who had observed courses believed more in their efficacy, with higher uptake within their clinic population. CONCLUSIONS: Social determinants of health, particularly educational attainment and gender, increase health inequalities by influencing decisions to attend evidence-based education courses. Healthcare professional communication is paramount to encourage attendance, and observation of a course may facilitate this.

6.
Eur Radiol ; 28(12): 5182-5194, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-29846804

RESUMO

PURPOSE: To compare the efficacy of use of digital breast tomosynthesis (DBT) with standard digital mammography (DM) workup views in the breast cancer assessment clinic. MATERIALS AND METHODS: The Tomosynthesis Assessment Clinic trial (TACT), conducted between 16 October 2014 and 19 April 2016, is an ethics-approved, monocenter, multireader, multicase split-plot reading study. After written informed consent was obtained, 144 females (age > 40 years) who were recalled to the assessment clinic were recruited into TACT. These cases (48 cancers) were randomly allocated for blinded review of (1) DM workup and (2) DBT, both in conjunction with previous DM from the screening examination. Fifteen radiologists of varying experience levels in the Australia BreastScreen Program were included in this study, wherein each radiologist read 48 cases (16 cancers) in 3 non-overlapping blocks. Diagnostic accuracy was measured by means of sensitivity, specificity, and positive (PPV) and negative predictive values (NPV). The receiver-operating characteristic area under the curve (AUC) was calculated to determine radiologists' performances. RESULTS: Use of DBT (AUC = 0.927) led to improved performance of the radiologists (z = 2.62, p = 0.008) compared with mammography workup (AUC = 0.872). Similarly, the sensitivity, specificity, PPV, and NPV of DBT (0.93, 0.75, 0.64, 0.96) were higher than those of the workup (0.90, 0.56, 0.49, 0.92). Most radiologists (80%) performed better with DBT than standard workup. Cancerous lesions on DBT appeared more severe (U = 33,172, p = 0.02) and conspicuous (U = 24,207, p = 0.02). There was a significant reduction in the need for additional views (χ2 = 17.63, p < 0.001) and recommendations for ultrasound (χ2 = 8.56, p = 0.003) with DBT. CONCLUSIONS: DBT has the potential to increase diagnostic accuracy and simplify the assessment process in the breast cancer assessment clinic. KEY POINTS: • Use of DBT in the assessment clinic results in increased diagnostic accuracy. • Use of DBT in the assessment clinic improves performance of radiologists and also increases the confidence in their decisions. • DBT may reduce the need for additional views, ultrasound imaging, and biopsy.


Assuntos
Neoplasias da Mama/diagnóstico , Mamografia/métodos , Programas de Rastreamento/métodos , Intensificação de Imagem Radiográfica/métodos , Austrália/epidemiologia , Neoplasias da Mama/epidemiologia , Feminino , Humanos , Incidência , Curva ROC
7.
Am J Transplant ; 16(11): 3212-3219, 2016 11.
Artigo em Inglês | MEDLINE | ID: mdl-27106124

RESUMO

Screening for de novo donor-specific antibodies (dnDSA) in stable kidney transplant recipients is routine practice in some centers. Patients with DSA are at increased risk of graft loss and early intervention may improve outcomes. However, the costs and benefits of dnDSA surveillance are unknown. A medical decision analysis to examine a screening strategy was developed for kidney transplant recipients who had stable graft function and were DSA negative 1 year posttransplant. In the base case, a modest 25% reduction in graft loss in dnDSA-positive patients treated with increased immunosuppression resulted in 0.04618 quality-adjusted years (QALYs) gained. However, benefits from reduced graft loss were eliminated if there was a small increased risk of death from added therapy. The incremental cost effectiveness was marginal at approximately $120 000-250 000 per QALY, but could be more or less favorable depending on several key variables such as efficacy of treatment, screening costs, incidence rate of subclinical dnDSA, and patient survival. Screening performed the best in patients with lower mortality rates and higher baseline incidence rates of dnDSA. Further study is warranted to gather the necessary high-quality evidence to justify screening.


Assuntos
Técnicas de Apoio para a Decisão , Rejeição de Enxerto/diagnóstico , Antígenos HLA/imunologia , Isoanticorpos/imunologia , Falência Renal Crônica/imunologia , Transplante de Rim/efeitos adversos , Doadores de Tecidos , Seguimentos , Taxa de Filtração Glomerular , Rejeição de Enxerto/etiologia , Sobrevivência de Enxerto , Humanos , Isoanticorpos/análise , Falência Renal Crônica/cirurgia , Testes de Função Renal , Complicações Pós-Operatórias , Prognóstico , Estudos Prospectivos , Fatores de Risco , Transplantados
8.
Curr Oncol ; 23(Suppl 1): S56-63, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26985148

RESUMO

BACKGROUND: In Canada, discussion about changing from cytology to human papillomavirus (hpv) dna testing for primary screening in cervical cancer is ongoing. However, the Canadian Task Force on Preventive Health Care has not yet made a recommendation, concluding that the evidence is insufficient. METHODS: We used the cervical cancer and hpv transmission models of the Cancer Risk Management Model to study the health and economic outcomes of primary cytology compared with hpv dna testing in 14 screening scenarios with varying screening modalities and intervals. Projected cervical cancer cases, deaths, colposcopies, screens, costs, and incremental cost-effectiveness were evaluated. We performed sensitivity analyses for hpv dna test costs. RESULTS: Compared with triennial cytology from age 25, 5-yearly hpv dna screening alone from age 30 resulted in equivalent incident cases and deaths, but 55% (82,000) fewer colposcopies and 43% (1,195,000) fewer screens. At hpv dna screening intervals of 3 years, whether alone or in an age-based sequence with cytology, screening costs are greater, but at intervals of more than 5 years, they are lower. Scenarios on the cost-effectiveness frontier were hpv dna testing alone every 10, 7.5, 5, or 3 years, and triennial cytology starting at age 21 or 25 when combined with hpv dna testing every 3 years. CONCLUSIONS: Changing from cytology to hpv dna testing as the primary screening test for cervical cancer would be an acceptable strategy in Canada with respect to incidence, mortality, screening and diagnostic test volumes.

9.
Breast ; 24(4): 440-8, 2015 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-25866350

RESUMO

In this paper, we study breast cancer screening policies using computer simulation. We developed a multi-state Markov model for breast cancer progression, considering both the screening and treatment stages of breast cancer. The parameters of our model were estimated through data from the Canadian National Breast Cancer Screening Study as well as data in the relevant literature. Using computer simulation, we evaluated various screening policies to study the impact of mammography screening for age-based subpopulations in Canada. We also performed sensitivity analysis to examine the impact of certain parameters on number of deaths and total costs. The analysis comparing screening policies reveals that a policy in which women belonging to the 40-49 age group are not screened, whereas those belonging to the 50-59 and 60-69 age groups are screened once every 5 years, outperforms others with respect to cost per life saved. Our analysis also indicates that increasing the screening frequencies for the 50-59 and 60-69 age groups decrease mortality, and that the average number of deaths generally decreases with an increase in screening frequency. We found that screening annually for all age groups is associated with the highest costs per life saved. Our analysis thus reveals that cost per life saved increases with an increase in screening frequency.


Assuntos
Neoplasias da Mama/diagnóstico , Análise Custo-Benefício/estatística & dados numéricos , Detecção Precoce de Câncer/economia , Mamografia/economia , Programas de Rastreamento/economia , Adulto , Fatores Etários , Idoso , Canadá , Simulação por Computador , Análise Custo-Benefício/métodos , Detecção Precoce de Câncer/mortalidade , Feminino , Humanos , Mamografia/mortalidade , Programas de Rastreamento/métodos , Pessoa de Meia-Idade , Modelos Teóricos , Fatores de Tempo
11.
Bone Joint J ; 95-B(1): 4-9, 2013 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-23307666

RESUMO

Staphylococcus aureus is one of the leading causes of surgical site infection (SSI). Over the past decade there has been an increase in methicillin-resistant S. aureus (MRSA). This is a subpopulation of the bacterium with unique resistance and virulence characteristics. Nasal colonisation with either S. aureus or MRSA has been demonstrated to be an important independent risk factor associated with the increasing incidence and severity of SSI after orthopaedic surgery. Furthermore, there is an economic burden related to SSI following orthopaedic surgery, with MRSA-associated SSI leading to longer hospital stays and increased hospital costs. Although there is some controversy about the effectiveness of screening and eradication programmes, the literature suggests that patients should be screened and MRSA-positive patients treated before surgical admission in order to reduce the risk of SSI.


Assuntos
Programas de Rastreamento/métodos , Staphylococcus aureus Resistente à Meticilina/isolamento & purificação , Procedimentos Ortopédicos , Cuidados Pré-Operatórios/métodos , Infecções Estafilocócicas/prevenção & controle , Infecção da Ferida Cirúrgica/prevenção & controle , Antibacterianos/economia , Antibacterianos/uso terapêutico , Antibioticoprofilaxia/economia , Infecções Comunitárias Adquiridas/diagnóstico , Infecções Comunitárias Adquiridas/tratamento farmacológico , Infecções Comunitárias Adquiridas/economia , Humanos , Programas de Rastreamento/economia , Staphylococcus aureus Resistente à Meticilina/patogenicidade , Mucosa Nasal/microbiologia , Procedimentos Ortopédicos/economia , Cuidados Pré-Operatórios/economia , Infecções Estafilocócicas/diagnóstico , Infecções Estafilocócicas/tratamento farmacológico , Infecções Estafilocócicas/economia , Infecção da Ferida Cirúrgica/economia , Estados Unidos , Virulência
12.
J BUON ; 17(2): 323-6, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-22740213

RESUMO

PURPOSE: To assist healthcare professionals in using the mini nutrition assessment (MNA) and its short-form (MNASF) for early identification of malnourished elderly lung cancer patients, conducting preoperative nutritional support, and improving patients' postoperative prognosis, quality of life, and survival. METHODS: The MNA with revised cut-off points to better suit the Chinese population was conducted on 103 elderly lung cancer Chinese patients aged 60 or above in the Tianjin Cancer Hospital prior to their scheduled surgery. Patient demographic data, anthropometric parameters, biochemical markers, and postoperative complications were collected and analysed. RESULTS: Of the 103 patients studied 12.6% (13/103) were malnourished, 31.1% (32/103) were at risk of malnutrition, and 56.3% (58/103) had adequate nutrition; the average MNA score was 23.6±3.7. Significant positive correlations were found between total MNA score and body mass index (BMI), mid-arm circumference (MAC), calf circumference (CC), and hemoglobin (Hb) (p<0.05), as well as between total MNA-SF score and BMI, MAC, CC, and total MNA score. Significant negative correlations occurred between total MNA-SF score and age (p<0.05). Among postoperative complications, cardiovascular diseases had the highest morbidity rate (23%), followed by respiratory diseases (22%), and cardiovascular and respiratory diseases combined (19%). No significant relationship between nutritional status with types of morbidity (p=0.235) and postoperative complications (p=0.362) was found. CONCLUSION: The MNA scale is an effective tool to preoperatively evaluate the nutritional status of elderly Chinese patients with lung cancer. These patients have poor nutritional status. Further investigations are needed to re-examine the correlation between the MNA results and postoperative complications.


Assuntos
Avaliação Geriátrica , Indicadores Básicos de Saúde , Neoplasias Pulmonares/cirurgia , Desnutrição , Complicações Pós-Operatórias , Qualidade de Vida , Idoso , Idoso de 80 Anos ou mais , Antropometria , Povo Asiático , Índice de Massa Corporal , Feminino , Seguimentos , Humanos , Neoplasias Pulmonares/complicações , Masculino , Pessoa de Meia-Idade , Avaliação Nutricional , Cuidados Pré-Operatórios , Prognóstico , Medição de Risco
13.
Mol Ecol Resour ; 12(3): 456-63, 2012 May.
Artigo em Inglês | MEDLINE | ID: mdl-22268566

RESUMO

Directly labelling locus-specific primers for microsatellite analysis is expensive and a common limitation to small-budget molecular ecology projects. More cost-effective end-labelling of PCR products can be achieved through a three primer PCR approach, involving a fluorescently labelled universal primer in combination with modified locus-specific primers with 5' universal primer sequence tails. This technique has been widely used but has been limited largely due to a lack of available universal primers suitable for co-amplifying large numbers of size overlapping loci and without requiring locus-specific PCR conditions to be modified. In this study, we report a suite of four high-performance universal primers that can be employed in a three primer PCR approach for efficient and cost-effective fluorescent end-labelling of PCR fragments. Amplification efficiency is maximized owing to high universal primer Tm values (approximately 60+ °C) that enhance primer versatility and enable higher annealing temperatures to be employed compared with commonly used universal primers such as M13. We demonstrate that these universal primers can be combined with multiple fluorophores to co-amplify multiple loci efficiently via multiplex PCR. This method provides a level of multiplexing and PCR efficiency similar to microsatellite fluorescent detection assays using directly labelled primers while dramatically reducing project costs. Primer performance is tested using several alternative PCR strategies that involve both single and multiple fluorophores in single and multiplex PCR across a wide range of taxa.


Assuntos
Primers do DNA/química , Primers do DNA/genética , Fluorescência , Corantes Fluorescentes/química , Tipagem Molecular/métodos , Reação em Cadeia da Polimerase/métodos , Coloração e Rotulagem/métodos , Custos e Análise de Custo , Genótipo , Tipagem Molecular/economia , Reação em Cadeia da Polimerase/economia , Coloração e Rotulagem/economia
14.
Microb Ecol ; 60(1): 55-68, 2010 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-20440490

RESUMO

This study is aimed to assess the formation of photosynthetic biofilms on and within different natural stone materials, and to analyse their biogeophysical and biogeochemical deterioration potential. This was performed by means of artificial colonisation under laboratory conditions during 3 months. Monitoring of microbial development was performed by image analysis and biofilm biomass estimation by chlorophyll extraction technique. Microscopy investigations were carried out to study relationships between microorganisms and the mineral substrata. The model applied in this work corroborated a successful survival strategy inside endolithic microhabitat, using natural phototrophic biofilm cultivation, composed by cyanobacteria and algae, which increased intrinsic porosity by active mineral dissolution. We observed the presence of mineral-like iron derivatives (e.g. maghemite) around the cells and intracellularly and the precipitation of hausmannite, suggesting manganese transformations related to the biomineralisation.


Assuntos
Biofilmes/crescimento & desenvolvimento , Materiais de Construção/microbiologia , Cianobactérias/crescimento & desenvolvimento , Eucariotos/crescimento & desenvolvimento , Biodegradação Ambiental , Clorofila/análise , Materiais de Construção/análise , Microscopia Eletrônica de Varredura , Fotossíntese , Porosidade
15.
Mult Scler ; 15(8): 984-97, 2009 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-19667023

RESUMO

BACKGROUND: The initial Multiple Sclerosis Functional Composite (MSFC) proposal was a three-part composite of quantitative measures of ambulation, upper extremity function, and cognitive function expressed as a single composite Z-score. However, the clinical meaning of an MSFC Z-score change is not obvious. This study instead used MSFC component data to define a patient-specific disease progression event. OBJECTIVE: Evaluate a new method for analyzing disability progression using the MSFC. METHODS: MSFC progression was defined as worsening from baseline on scores of at least one MSFC component by 20% (MSFC Progression-20) or 15% (MSFC Progression-15), sustained for >or=3 months. Progression rates were determined using data from natalizumab clinical studies (Natalizumab Safety and Efficacy in Relapsing Remitting Multiple Sclerosis [AFFIRM] and Safety and Efficacy of Natalizumab in Combination With Interferon Beta-1a in Patients With Relapsing Remitting Multiple Sclerosis [SENTINEL]). Correlations between MSFC progression and other clinical measures were determined, as was sensitivity to treatment effects. RESULTS: Substantial numbers of patients met MSFC progression criteria, with MSFC Progression-15 being more sensitive than MSFC Progression-20, at both 1 and 2 years. MSFC Progression-20 and MSFC Progression-15 were related significantly to Expanded Disability Status Scale (EDSS) score change, relapse rate, and the SF-36 Physical Component Summary (PCS) score change. MSFC Progression-20 and MSFC Progression-15 at 1 year were predictive of EDSS progression at 2 years. Both MSFC progression end points demonstrated treatment effects in AFFIRM, and results were replicated in SENTINEL. CONCLUSION: MSFC Progression-20 and MSFC Progression-15 are sensitive measures of disability progression; correlate with EDSS, relapse rates, and SF-36 PCS; and are capable of demonstrating therapeutic effects in randomized, controlled clinical studies.


Assuntos
Avaliação da Deficiência , Indicadores Básicos de Saúde , Esclerose Múltipla Recidivante-Remitente/diagnóstico , Adulto , Anticorpos Monoclonais/uso terapêutico , Anticorpos Monoclonais Humanizados , Cognição , Progressão da Doença , Quimioterapia Combinada , Feminino , Humanos , Fatores Imunológicos/uso terapêutico , Interferon beta-1a , Interferon beta/uso terapêutico , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Esclerose Múltipla Recidivante-Remitente/tratamento farmacológico , Esclerose Múltipla Recidivante-Remitente/fisiopatologia , Esclerose Múltipla Recidivante-Remitente/psicologia , Natalizumab , Valor Preditivo dos Testes , Modelos de Riscos Proporcionais , Ensaios Clínicos Controlados Aleatórios como Assunto , Recidiva , Sensibilidade e Especificidade , Fatores de Tempo , Resultado do Tratamento , Extremidade Superior/fisiopatologia , Caminhada
17.
Stud Mycol ; 64: 1-15S10, 2009.
Artigo em Inglês | MEDLINE | ID: mdl-20169021

RESUMO

We present a comprehensive phylogeny derived from 5 genes, nucSSU, nucLSU rDNA, TEF1, RPB1 and RPB2, for 356 isolates and 41 families (six newly described in this volume) in Dothideomycetes. All currently accepted orders in the class are represented for the first time in addition to numerous previously unplaced lineages. Subclass Pleosporomycetidae is expanded to include the aquatic order Jahnulales. An ancestral reconstruction of basic nutritional modes supports numerous transitions from saprobic life histories to plant associated and lichenised modes and a transition from terrestrial to aquatic habitats are confirmed. Finally, a genomic comparison of 6 dothideomycete genomes with other fungi finds a high level of unique protein associated with the class, supporting its delineation as a separate taxon.

18.
J Bone Joint Surg Br ; 91(1): 131-7, 2009 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-19092018

RESUMO

In spite of extensive accounts describing the blood supply to the femoral head, the prediction of avascular necrosis is elusive. Current opinion emphasises the contributions of the superior retinacular artery but may not explain the clinical outcome in many situations, including intramedullary nailing of the femur and resurfacing of the hip. We considered that significant additional contribution to the vascularity of the femoral head may exist. A total of 14 fresh-frozen hips were dissected and the medial circumflex femoral artery was cannulated in the femoral triangle. On the test side, this vessel was ligated, with the femoral head receiving its blood supply from the inferior vincular artery alone. Gadolinium contrast-enhanced MRI was then performed simultaneously on both control and test specimens. Polyurethane was injected, and gross dissection of the specimens was performed to confirm the extraosseous anatomy and the injection of contrast. The inferior vincular artery was found in every specimen and had a significant contribution to the vascularity of the femoral head. The head was divided into four quadrants: medial (0), superior (1), lateral (2) and inferior (3). In our study specimens the inferior vincular artery contributed a mean of 56% (25% to 90%) of blood flow in quadrant 0, 34% (14% to 80%) of quadrant 1, 37% (18% to 48%) of quadrant 2 and 68% (20% to 98%) in quadrant 3. Extensive intra-osseous anastomoses existed between the superior retinacular arteries, the inferior vincular artery and the subfoveal plexus.


Assuntos
Artéria Femoral/fisiologia , Necrose da Cabeça do Fêmur/fisiopatologia , Cabeça do Fêmur/irrigação sanguínea , Imageamento por Ressonância Magnética/métodos , Cadáver , Meios de Contraste , Artéria Femoral/anatomia & histologia , Gadolínio DTPA , Humanos , Fluxo Sanguíneo Regional/fisiologia
19.
J Anim Sci ; 87(4): 1261-9, 2009 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-19098231

RESUMO

Short and long-term effects of manipulating dietary CP content and diet quality in weaner diets on health and performance of pigs were investigated in a 2 x 2 factorial combination of CP inclusion (high-CP, 230 g of CP/kg vs. low-CP, 170 g of CP/kg) and diet quality (high-quality, cooked cereals, and animal protein vs. low-quality, raw cereals, and plant protein). Diets were fed ad libitum for 14 d postweaning to pigs weaned at 29.4+/-3.1 d of age and 9.9+/-1.0 kg of BW. From d 14 to slaughter at 104+/-3 kg, all pigs were fed the same series of standard commercial diets. There were 15 replicates per treatment in the weaner phase (<30 kg) and 5 replicates per treatment in the grower-finisher phase (>30 kg). High-quality diets promoted gut health as indicated by improved fecal lactobacilli to coliform ratio (P=0.002) and decreased fecal enterotoxigenic Escherichia coli counts on d 11 postweaning (P=0.028), reducing the risk of postweaning diarrhea and improving pig health from weaning to the end of the weaner phase. Reducing CP content had no effect on gut health. High-CP (P=0.053) and high-quality (P=0.025) diets independently increased ADG during the first 14 d postweaning compared with low-CP and low-quality diets, respectively. There were no interactions between dietary CP content and quality on any of the response criteria investigated. Despite differences in the immediate postweaning period, there was no effect of manipulating diet quality or CP content for 2 wk postweaning on lifetime performance with pigs reaching slaughter weight in 128+/-7 d. These results indicate that high-quality diets may protect pig gut health during the immediate postweaning period. However, it may be possible to use less expensive, decreased quality weaner diets without any adverse effects on long-term performance when weaning older, heavier pigs and where health status, environmental control, and stock management are all maintained to a high standard.


Assuntos
Criação de Animais Domésticos/métodos , Dieta/veterinária , Proteínas Alimentares/administração & dosagem , Suínos/crescimento & desenvolvimento , Desmame , Criação de Animais Domésticos/economia , Animais , Composição Corporal , Contagem de Colônia Microbiana , Dieta/economia , Dieta/normas , Ingestão de Alimentos/fisiologia , Escherichia coli/fisiologia , Fezes/microbiologia , Feminino , Masculino , Distribuição Aleatória , Aumento de Peso/fisiologia
20.
Br J Surg ; 95(3): 369-74, 2008 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-17932877

RESUMO

BACKGROUND: The UK government's fast-track 2-week wait (2WW) rule and colorectal cancer guidelines aimed to detect patients at high risk of having colorectal cancer, but the yield has been poor. A patient consultation questionnaire (PCQ)-based scoring system may be an effective tool for prioritizing colorectal referrals. The aim of this study was to validate the system in a large and ethnically diverse population and to compare it with 2WW referrals. METHODS: Over a 1-year period, all colorectal referrals (2WW and traditional letters) at nine hospitals in Leicestershire were sent a PCQ to complete and return. A weighted numerical score (WNS), which reflects the patient's risk of having colorectal cancer, was calculated and compared with the hospital diagnosis. RESULTS: Of a total of 1422 PCQs returned, 83 patients were diagnosed with colorectal cancer. The 2WW referrals constituted 35.7 per cent of all referrals. The mean WNS of patients with colorectal cancer was significantly higher than that of the other patients (mean 76.3 versus 48.9 respectively; P < 0.001). For similar cancer detection rates (or sensitivity), the specificity of a WNS cut-off of 70 was significantly better than that of the 2WW system (82.7 versus 66.1 per cent; P < 0.001). CONCLUSION: The PCQ-based WNS system improves specificity for detecting colorectal cancer, particularly when the WNS exceeds 70.


Assuntos
Neoplasias Colorretais/diagnóstico , Inquéritos e Questionários/normas , Adulto , Idoso , Idoso de 80 Anos ou mais , Assistência Ambulatorial/normas , Inglaterra , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Encaminhamento e Consulta/normas , Medição de Risco/métodos , Medição de Risco/normas , Sensibilidade e Especificidade
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