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1.
Eur J Oncol Nurs ; 71: 102610, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38914026

RESUMO

INTRODUCTION: Healthcare professionals are vital in preparing people living with and beyond cancer about the risks of chronic pain after cancer treatment. To do so, healthcare professionals need to be knowledgeable and confident about chronic pain after cancer treatment, yet little is known about their understanding or confidence of this common long-term and late side effect of cancer treatment. AIM: To identify healthcare professionals' knowledge and understanding of chronic pain after cancer treatment and consider how confident they are to inform, listen and signpost people living with and beyond cancer to appropriate information and support. METHOD: A cross sectional online survey was distributed to healthcare professionals in the UK via cancer and primary care networks, cancer alliances and social media. The survey consisted of four domains: 1) knowledge and understanding, 2) information and support, 3) confidence and 4) barriers. Quantitative data were analysed with descriptive statistics and free text comments were analysed using qualitative content analysis. RESULTS: Healthcare professionals reported limited knowledge and understanding of chronic pain after cancer treatment. Healthcare professionals lacked confidence to talk to people about chronic pain after cancer treatment and viewed their lack of knowledge as a barrier. Additional barriers included 'Limited service provision', 'Conflict between services', 'Not my role' and 'Challenges in diagnosing chronic pain in cancer survivors'. CONCLUSION: Chronic pain after cancer can be a significant issue for those living with and beyond cancer, yet healthcare professionals report limited knowledge of it or understanding of the impact. More education is needed to increase healthcare professionals' knowledge and confidence in chronic pain after cancer treatment.


Assuntos
Dor Crônica , Conhecimentos, Atitudes e Prática em Saúde , Neoplasias , Humanos , Estudos Transversais , Reino Unido , Dor Crônica/terapia , Masculino , Feminino , Neoplasias/complicações , Inquéritos e Questionários , Adulto , Pessoa de Meia-Idade , Pessoal de Saúde/psicologia , Manejo da Dor/métodos , Atitude do Pessoal de Saúde
2.
Sci Rep ; 13(1): 10896, 2023 07 05.
Artigo em Inglês | MEDLINE | ID: mdl-37407631

RESUMO

A novel method aimed at evaluating the active drag profile during front-crawl swimming is proposed. Fourteen full trials were conducted with each trial using a stationary load cell set-up and a commercial resistance trainer to record the tension force in a rope, caused by an athlete swimming. Seven different stroke cycles in each experiment were identified for resampling time dependent data into position dependent data. Active drag was then calculated by subtracting resistance trainer force data away from the stationary load cell force data. Mean active drag values across the stroke cycle were calculated for comparison with existing methods, with mean active drag values calculated between 76 and 140 N depending on the trial. Comparing results with established active drag methods, such as the Velocity Perturbation Method (VPM), shows agreement in the magnitude of the mean active drag forces. Repeatability was investigated using one athlete, repeating the load cell set-up experiment, indicating results collected could range by 88 N depending on stroke cycle position. Variation in results is likely due to inconsistencies in swimmer technique and power output, although further investigation is required. The method outlined is proposed as a representation of the active drag profile over a full stroke cycle.


Assuntos
Fenômenos Mecânicos , Natação , Humanos , Fenômenos Biomecânicos , Gravitação
3.
BMJ Mil Health ; 169(e1): e34-e38, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-33483453

RESUMO

INTRODUCTION: The 'golden hour' is a universal paradigm that suggests trauma patients have lower morbidity and mortality when provided with medical care within 1 hour after injury. The objective of this study was to examine whether transport time from point of injury to a military treatment facility (MTF) in-theatre was associated with patient-reported outcomes, such as post-traumatic stress disorder (PTSD), depression and quality of life (QOL), among US service members with combat-related injury. METHODS: Participants were injured between March 2003 and March 2016 and completed standardised assessments of PTSD, depression and QOL for theWounded Warrior Recovery Project (WWRP) between January 2013 and November 2017. Multivariable regressions were used to assess the relationship between transport time (≤1 hour or >1 hour from injury to MTF) and positive screens for PTSD and depression, and QOL, respectively.Overall, 45.6% of participants (n=879) arrived at an MTF within 1 hour postinjury. About 8 years passed between when participants were injured on deployment and when they completed their first WWRP assessment. Approximately 48% of participants screened positive for PTSD and 51.3% for depression, with a mean QOL score of 0.513 (SD=0.150). After adjusting for covariates, transport time was not significantly associated with PTSD (OR 1.04, 95% CI 0.79 to 1.38; p=0.77), depression (OR 0.92, 95% CI 0.69 to 1.21; p=0.55) or QOL (ß=0.009; p=0.38). CONCLUSION: Transport time was not associated with patient-reported outcomes among US service members with combat-related injury. These findings are important as we seek to understand how combat casualties may be affected by extended medical evacuation or transport times anticipated in future expeditionary operations.


Assuntos
Militares , Transtornos de Estresse Pós-Traumáticos , Humanos , Qualidade de Vida , Campanha Afegã de 2001- , Medidas de Resultados Relatados pelo Paciente
4.
S Afr J Sports Med ; 35(1): v35i1a15080, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38249765

RESUMO

Background: Despite an increase in the professionalism and participation of female cricket, the coaching of female pace bowling is still reliant on male-derived knowledge. Objectives: To investigate the association between key male-derived kinematic and anthropometric parameters and ball release speed (BRS) in female pace bowlers. Methods: Eleven female pace bowlers participated in this study. BRS, and four anthropometric and five kinematic parameters were determined. Stepwise linear regression and Pearson Product Moment correlations were used to identify anthropometric and kinematic parameters linked to BRS. Results: The best predictor of BRS explaining 89% of the observed variance was the bowling shoulder angle at ball release. The best anthropometric predictor of BRS was height explaining 53% of the observed variance. Other parameters correlated with BRS included: run-up speed (r = 0.75, p = 0.013) and arm length (r = 0.61, p = 0.046). When height was controlled for, the front knee angle at front foot contact was also correlated to BRS (r = 0.68, p = 0.044). No relationship was found between trunk flexion and BRS. Conclusion: Faster BRS were characterised by faster run-up speeds, straighter front knees, and delayed arm circumduction similar to male pace bowlers. The lack of relationship between trunk flexion and BRS may highlight female pace bowlers adopting a bowling technique where BRS is contributed to by trunk rotation as well as trunk flexion. This knowledge is likely to be useful in the talent identification and coaching of female pace bowlers.

5.
J Dairy Sci ; 105(10): 8558-8568, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-36055843

RESUMO

The US dairy industry has made substantial gains in reducing the greenhouse gas emission intensity of a gallon of milk. At the same time, consumer and investor interest for improved environmental benefits or reduced environmental impact of food production continues to grow. Following a trend of increasing greenhouse gas emission commitments for businesses across sectors of the economy, the US dairy industry has committed to a goal of net zero greenhouse gas emissions by 2050. The Paris Climate Accord's goal is to reduce warming of the atmosphere to less than 1.5 to 2°C based on preindustrial levels, which is different from emission goals of historic climate agreements that focus on emission reduction targets. Most of the emissions that account for the greenhouse gas footprint of a gallon of milk are from the short-lived climate pollutant CH4, which has a half-life of approximately 10 yr. The relatively new accounting system Global Warming Potential Star and the unit CO2 warming equivalents gives the industry the appropriate metrics to quantify their current and projected warming impact on future emissions. Incorporating this metric into potential future emissions pathways can allow the industry to understand the magnitude of emissions reductions needed to no longer contribute additional warming. Deterministic modeling was performed across the dairy industry's emission areas of enteric fermentation, manure management, feed production, and other upstream emissions necessary for dairy production. By reducing farm-level absolute emissions by 23% based on current levels, there is the opportunity for the US dairy industry to realize climate neutrality within the next few decades.


Assuntos
Gases de Efeito Estufa , Animais , Dióxido de Carbono/análise , Bovinos , Indústria de Laticínios , Gases de Efeito Estufa/metabolismo , Esterco/análise , Leite/química
6.
Science ; 371(6527): 386-390, 2021 01 22.
Artigo em Inglês | MEDLINE | ID: mdl-33479150

RESUMO

Convergent evolution provides insights into the selective drivers underlying evolutionary change. Snake venoms, with a direct genetic basis and clearly defined functional phenotype, provide a model system for exploring the repeated evolution of adaptations. While snakes use venom primarily for predation, and venom composition often reflects diet specificity, three lineages of cobras have independently evolved the ability to spit venom at adversaries. Using gene, protein, and functional analyses, we show that the three spitting lineages possess venoms characterized by an up-regulation of phospholipase A2 (PLA2) toxins, which potentiate the action of preexisting venom cytotoxins to activate mammalian sensory neurons and cause enhanced pain. These repeated independent changes provide a fascinating example of convergent evolution across multiple phenotypic levels driven by selection for defense.


Assuntos
Venenos Elapídicos/enzimologia , Elapidae/classificação , Elapidae/genética , Evolução Molecular , Fosfolipases A2 do Grupo IV/genética , Dor , Células Receptoras Sensoriais/fisiologia , Adaptação Biológica/genética , Animais , Venenos Elapídicos/genética , Filogenia , Células Receptoras Sensoriais/metabolismo
7.
J Dairy Sci ; 104(2): 2422-2437, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33309361

RESUMO

Circadian and metabolic systems are interlocked and reciprocally regulated. To determine if the circadian system regulates glucose homeostasis and mammary development, the function of the circadian system was disrupted by exposing cattle to chronic light-dark cycle phase shifts from 5 wk before expected calving (BEC) to parturition. Multiparous Holstein cows were exposed to 16 h of light and 8 h of dark (CON, n = 8) or phase shifting (PS, n = 8) the light cycle 6 h every 3 d beginning 35 d BEC. After calving, both treatments were exposed to CON lighting. Mammary biopsies were taken at 21 d BEC and 21 d in milk (DIM), and histological analysis indicated PS treatment decreased the ratio of lumen to alveolar area and percentage of proliferating epithelial cells in the prepartum period. Intravenous glucose tolerance test was performed at 14 d BEC and 7 DIM by administering 50% dextrose. Blood glucose, ß-hydroxybutyrate, insulin, and nonesterified fatty acids were consequently measured over 3 h. At 14 d BEC no treatment differences were observed in baseline glucose or insulin. Treatment had no effect on blood glucose or glucose area under the curve at 14 d BEC and 7 DIM. Insulin area under the curve was higher in PS versus CON at 14 d BEC and 7 DIM. The PS cows produced less milk than CON cows through 60 DIM (40.3 vs. 42.6 kg/d). Exposure to chronic light-dark PS in late gestation decreased mammary development and increased insulin resistance in periparturient cows, which may have caused subsequent lower milk yield.


Assuntos
Bovinos , Relógios Circadianos , Resistência à Insulina , Glândulas Mamárias Animais/crescimento & desenvolvimento , Leite , Período Pós-Parto , Ácido 3-Hidroxibutírico/sangue , Animais , Glicemia/metabolismo , Escuridão , Ácidos Graxos não Esterificados/sangue , Feminino , Teste de Tolerância a Glucose/veterinária , Insulina/sangue , Lactação/fisiologia , Luz , Parto , Gravidez
9.
Pediatr Surg Int ; 36(9): 1111-1116, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32524188

RESUMO

PURPOSE: To assess the impact of modifications in preoperative instructions on parental understanding of preoperative fasting guidelines. METHODS: A prospective postoperative parental survey was conducted to assess parental understanding of preoperative fasting requirements in patients undergoing surgery before and after institution of instructions that included visual aids. Data regarding demographics, procedure type, and time to surgery from preoperative visit were also captured. Survey data were compared between pre- and post-intervention groups using Chi-squared tests for categorical variables and Wilcoxon rank sum test for continuous variables. RESULTS: 173 parents in the pre-intervention group and 162 parents in the post-intervention group were included in the analysis. Parent identification of aspiration risk as the reason for fasting almost doubled after intervention (72.2% vs. 38.2%). There was some evidence of demographic differences between groups; however, in an adjusted model, there was strong evidence (p < 0.001) that parents in the post-intervention group were more likely to identify aspiration as the reason for preoperative fasting (OR 4.73; 95% CI 2.93-7.63). CONCLUSIONS: Addition of visual aids in preoperative instructions was associated with improvement in parents' understanding of the rationale behind preoperative fasting instructions. Further studies are needed to determine whether improved understanding is associated with improved adherence.


Assuntos
Jejum , Pacientes Ambulatoriais , Pais , Cuidados Pré-Operatórios/métodos , Procedimentos Cirúrgicos Urológicos/métodos , Pré-Escolar , Feminino , Humanos , Masculino , Período Pós-Operatório , Estudos Prospectivos , Inquéritos e Questionários
11.
Int J Cardiol ; 293: 218-222, 2019 10 15.
Artigo em Inglês | MEDLINE | ID: mdl-31126734

RESUMO

BACKGROUND: The systolic to diastolic (SD) duration ratio reflects global RV performance in pulmonary arterial hypertension (PAH) yet limited data exists on its application to adult non-congenital PAH. We measured SD ratios on echocardiogram in idiopathic PAH (IPAH) to establish its response to pulmonary vasodilator therapy and prognostic value at diagnosis and follow up. METHODS: Incident patients with IPAH undergoing echocardiogram, haemodynamic and exercise assessments were identified within our centre between 2005 and 2018. SD ratios were adjusted for heart rate at diagnosis and follow up. RESULTS: In 98 patients at diagnosis, the mean SD ratio was 1.03 ±â€¯0.37 decreasing to 0.85 ±â€¯0.25, p < 0.001 at follow-up echocardiogram performed at a median interval of 9.0 months. The SD ratio at diagnosis correlated weakly with RV basal diameter (r = 0.24, p = 0.04) and 6MWD (r = 0.23, p = 0.04). At follow up, the mean SD ratio was lower in those receiving combination vs monotherapy pulmonary vasodilator treatment (71 ±â€¯25 vs 92 ±â€¯22% baseline respectively, p < 0.001). After a median follow-up of 4.8 years, 3 patients were transplanted and 23 patients died. The SD ratio at diagnosis and follow up predicted an increased risk of death/transplantation (HR 2.41 (1.09-5.29), p = 0.03; HR 5.02 (1.27-19.77), p = 0.02 respectively), retaining its predictive value at diagnosis in bivariate models with 6MWD (HR 2.18 (1.06-4.08)), WHO Functional Class (HR 2.33 (1.04-5.21)) and TAPSE (HR 2.36 (1.07-5.19)), all p < 0.05. CONCLUSIONS: The SD ratio carries prognostic value at diagnosis and follow up in IPAH. Its further evaluation alongside current PAH risk stratification parameters should be considered.


Assuntos
Diástole , Ecocardiografia/métodos , Hipertensão Pulmonar Primária Familiar , Ventrículos do Coração , Sístole , Adulto , Hipertensão Pulmonar Primária Familiar/diagnóstico , Hipertensão Pulmonar Primária Familiar/mortalidade , Hipertensão Pulmonar Primária Familiar/fisiopatologia , Hipertensão Pulmonar Primária Familiar/cirurgia , Feminino , Seguimentos , Transplante de Coração/estatística & dados numéricos , Ventrículos do Coração/diagnóstico por imagem , Ventrículos do Coração/fisiopatologia , Humanos , Masculino , Pessoa de Meia-Idade , Mortalidade , Valor Preditivo dos Testes , Prognóstico , Medição de Risco/métodos
12.
Sci Rep ; 9(1): 3154, 2019 02 28.
Artigo em Inglês | MEDLINE | ID: mdl-30816157

RESUMO

The counter-regulatory axis, Angiotensin Converting Enzyme 2, Angiotensin-(1-7), Mas receptor (ACE2/Ang-1-7/MasR), of the renin angiotensin system (RAS) is a potential therapeutic target in stroke, with Ang-(1-7) reported to have neuroprotective effects in pre-clinical stroke models. Here, an extensive investigation of the functional and mechanistic effects of Ang-(1-7) was performed in a rodent model of stroke. Using longitudinal magnetic resonance imaging (MRI) it was observed that central administration of Ang-(1-7) following transient middle cerebral artery occlusion (MCAO) increased the amount of tissue salvage compared to reperfusion alone. This protective effect was not due to early changes in blood brain barrier (BBB) permeability, microglia activation or inflammatory gene expression. However, increases in NADPH oxidase 1 (Nox1) mRNA expression were observed in the treatment group compared to control. In order to determine whether Ang-(1-7) has direct cerebrovascular effects, laser speckle contrast imaging (LSCI) was performed to measure dynamic changes in cortical perfusion following reperfusion. Delivery of Ang-(1-7) did not have any effect on cortical perfusion following reperfusion however; it showed an indication to prevent the 'steal phenomenon' within the contralateral hemisphere. The comprehensive series of studies have demonstrated a moderate protective effect of Ang-(1-7) when given alongside reperfusion to increase tissue salvage.


Assuntos
Angiotensina I/farmacologia , Infarto da Artéria Cerebral Média/tratamento farmacológico , NADPH Oxidase 1/genética , Fragmentos de Peptídeos/farmacologia , Peptidil Dipeptidase A/genética , Acidente Vascular Cerebral/tratamento farmacológico , Enzima de Conversão de Angiotensina 2 , Animais , Barreira Hematoencefálica/efeitos dos fármacos , Meios de Contraste/farmacologia , Modelos Animais de Doenças , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , Infarto da Artéria Cerebral Média/diagnóstico por imagem , Infarto da Artéria Cerebral Média/genética , Infarto da Artéria Cerebral Média/fisiopatologia , Inflamação/diagnóstico por imagem , Inflamação/tratamento farmacológico , Inflamação/genética , Inflamação/patologia , Imageamento por Ressonância Magnética , Microglia/efeitos dos fármacos , Microglia/patologia , Artéria Cerebral Média/diagnóstico por imagem , Artéria Cerebral Média/efeitos dos fármacos , Fármacos Neuroprotetores , Proto-Oncogene Mas , RNA Mensageiro/genética , Ratos , Sistema Renina-Angiotensina/genética , Reperfusão/métodos , Acidente Vascular Cerebral/diagnóstico por imagem , Acidente Vascular Cerebral/genética , Acidente Vascular Cerebral/patologia
13.
Schmerz ; 32(3): 195-200, 2018 06.
Artigo em Alemão | MEDLINE | ID: mdl-29736619

RESUMO

BACKGROUND: Besides the classical clinical manifestations, body perception disturbances are common among patients with complex regional pain syndrome (CRPS). The Bath Body Perception Disturbance Scale (BBPDS) represents a useful tool to assess these changes in CRPS patients; however, to date no validated German version is available. OBJECTIVE: The aim of this study was to translate the BBPDS into German, to perform a cross-cultural adaptation and linguistic validation in patients with acute (symptoms <3 months) and stable (symptoms ≥3 months) CRPS. MATERIAL AND METHODS: The original English version of the BBPDS was translated into German according to published guidelines (translation and back translation) and tested on 56 patients (mean age 50.9 ± 13.1 years) with acute (n = 28) or stable (n = 28) CRPS. RESULTS: The relative reliability, intraclass correlation and test-retest reliability were excellent overall and in the groups with acute and stable CRPS. The smallest detectable change was at 10 points. In the test-retest 48 points lay within the 95% confidence interval and visual inspection showed no tendency towards heteroscedasticity. Spearman's ρ­coefficient values showed no correlation between the total score of the BBPDS-D with the numerical rating scale (NRS, ρ = -0.19) and the EuroQol-5 D (ρ = 0.16). There were no significant differences between patients with acute and stable CRPS (p = 0.412). There were also no floor or ceiling effects. CONCLUSION: This German translation and cross-cultural adaptation of the original English version of the BBPDS is a valid instrument to assess body perception disturbances in German speaking CRPS patients. Future research should further assess the impact of body perception disturbance on treatment outcome and prognosis.


Assuntos
Síndromes da Dor Regional Complexa , Comparação Transcultural , Adulto , Avaliação da Deficiência , Humanos , Linguística , Pessoa de Meia-Idade , Psicometria , Reprodutibilidade dos Testes , Inquéritos e Questionários
14.
Eur J Pain ; 22(3): 551-564, 2018 03.
Artigo em Inglês | MEDLINE | ID: mdl-29194871

RESUMO

BACKGROUND: Complex Regional Pain Syndrome (CRPS) symptoms can significantly differ between patients, fluctuate over time, disappear or persist. This leads to problems in defining recovery and in evaluating the efficacy of therapeutic interventions. OBJECTIVES: To define recovery from the patients' perspective and better understand their priorities for treatment approaches. METHODS: Establishing an international consortium, we used a 2-Round Delphi-based study in eight countries across Europe and North America. Participants ≥18 years who met, or had met, Budapest clinical criteria were included. Round 1 participants completed the statement: 'I would/do consider myself recovered from CRPS if/because…' alongside demographic and health questionnaires. Data were thematically organised and represented as 62 statements, from which participants identified and ranked their recovery priorities in Round 2. RESULTS: Round 1 (N = 347, 80% female, 91% non-recovered) dominant ICF themes were: activities of daily living; bodily functions; external factors; participation and personal factors. The top five priority statements in Round 2 (N = 252) were: no longer having (1) CRPS-related pain, (2) generalised pain and discomfort, (3) restricted range of movement, (4) need for medication, (5) stiffness in the affected limb. With very few exceptions, priorities were consistent, irrespective of patient demographics/geography. Symptoms affecting daily activities were among those most frequently reported. CONCLUSIONS: Our data showed a small number of themes are of highest importance to CRPS patients' definition of recovery. Patients want their pain, movement restriction and reliance on medication to be addressed, above all other factors. These factors should therefore be foremost concerns for future treatment and rehabilitation programmes. SIGNIFICANCE: Those with longstanding CRPS may no longer meet diagnostic criteria but still be symptomatic. Defining recovery is therefore problematic in CRPS. Our study has identified patients' definition of recovery from CRPS, in order of priority, as relief from: their CRPS-related pain, generalised pain, movement restriction, reliance on medication, and stiffness.


Assuntos
Atividades Cotidianas , Síndromes da Dor Regional Complexa/fisiopatologia , Medidas de Resultados Relatados pelo Paciente , Recuperação de Função Fisiológica , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Analgésicos/uso terapêutico , Síndromes da Dor Regional Complexa/tratamento farmacológico , Técnica Delphi , Europa (Continente) , Extremidades , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Medição da Dor , Pesquisa Qualitativa , Amplitude de Movimento Articular , Adulto Jovem
15.
Eur J Cancer ; 85: 6-14, 2017 11.
Artigo em Inglês | MEDLINE | ID: mdl-28881249

RESUMO

BACKGROUND: A recent large United Kingdom (UK) clinical trial demonstrated that positron-emission tomography-computed tomography (PET-CT)-guided administration of neck dissection (ND) in patients with advanced head and neck cancer after primary chemo-radiotherapy treatment produces similar survival outcomes to planned ND (standard care) and is cost-effective over a short-term horizon. Further assessment of long-term outcomes is required to inform a robust adoption decision. Here we present results of a lifetime cost-effectiveness analysis of PET-CT-guided management from a UK secondary care perspective. METHODS: Initial 6-month cost and health outcomes were derived from trial data; subsequent incidence of recurrence and mortality was simulated using a de novo Markov model. Health benefit was measured in quality-adjusted life years (QALYs) and costs reported in 2015 British pounds. Model parameters were derived from trial data and published literature. Sensitivity analyses were conducted to assess the impact of uncertainty and broader National Health Service (NHS) and personal social services (PSS) costs on the results. RESULTS: PET-CT management produced an average per-person lifetime cost saving of £1485 and an additional 0.13 QALYs. At a £20,000 willingness-to-pay per additional QALY threshold, there was a 75% probability that PET-CT was cost-effective, and the results remained cost-effective over the majority of sensitivity analyses. When adopting a broader NHS and PSS perspective, PET-CT management produced an average saving of £700 and had an 81% probability of being cost-effective. CONCLUSIONS: This analysis indicates that PET-CT-guided management is cost-effective in the long-term and supports the case for wide-scale adoption.


Assuntos
Carcinoma de Células Escamosas/diagnóstico por imagem , Carcinoma de Células Escamosas/economia , Neoplasias de Cabeça e Pescoço/diagnóstico por imagem , Neoplasias de Cabeça e Pescoço/economia , Custos de Cuidados de Saúde , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/economia , Carcinoma de Células Escamosas/mortalidade , Carcinoma de Células Escamosas/terapia , Quimiorradioterapia Adjuvante/economia , Simulação por Computador , Redução de Custos , Análise Custo-Benefício , Técnicas de Apoio para a Decisão , Feminino , Neoplasias de Cabeça e Pescoço/mortalidade , Neoplasias de Cabeça e Pescoço/terapia , Humanos , Masculino , Cadeias de Markov , Modelos Econômicos , Esvaziamento Cervical/economia , Terapia Neoadjuvante/economia , Valor Preditivo dos Testes , Anos de Vida Ajustados por Qualidade de Vida , Atenção Secundária à Saúde/economia , Carcinoma de Células Escamosas de Cabeça e Pescoço , Medicina Estatal/economia , Fatores de Tempo , Resultado do Tratamento , Reino Unido
16.
Endocr Relat Cancer ; 24(9): 459-474, 2017 09.
Artigo em Inglês | MEDLINE | ID: mdl-28676500

RESUMO

Pituitary tumor-transforming gene 1-binding factor (PTTG1IP; PBF) is a multifunctional glycoprotein, which is overexpressed in a wide range of tumours, and significantly associated with poorer oncological outcomes, such as early tumour recurrence, distant metastasis, extramural vascular invasion and decreased disease-specific survival. PBF transforms NIH 3T3 fibroblasts and induces tumours in nude mice, while mice harbouring transgenic thyroidal PBF expression show hyperplasia and macrofollicular lesions. Our assumption that PBF becomes an oncogene purely through increased expression has been challenged by the recent report of mutations in PBF within the Catalogue of Somatic Mutations in Cancer (COSMIC) database. We therefore sought to determine whether the first 10 PBF missense substitutions in human cancer might be oncogenic. Anisomycin half-life studies revealed that most mutations were associated with reduced protein stability compared to wild-type (WT) PBF. Proliferation assays narrowed our interest to two mutational events which significantly altered cell turnover: C51R and R140W. C51R was mainly confined to the endoplasmic reticulum while R140W was apparent in the Golgi apparatus. Both C51R and R140W lost the capacity to induce cellular migration and significantly reduced cell invasion. Colony formation and soft agar assays demonstrated that, in contrast to WT PBF, both mutants were unable to elicit significant colony formation or anchorage-independent growth. However, C51R and R140W retained the ability to repress radioiodide uptake, a functional hallmark of PBF. Our data reveal new insight into PBF function and confirm that, rather than being oncogenic, mutations in PBF are likely to be passenger effects, with overexpression of PBF the more important aetiological event in human cancer.


Assuntos
Proteínas de Membrana/genética , Animais , Proliferação de Células , Humanos , Peptídeos e Proteínas de Sinalização Intracelular , Proteínas de Membrana/metabolismo , Camundongos , Mutação , Proto-Oncogene Mas , Transfecção
17.
Oncogene ; 36(37): 5296-5308, 2017 09 14.
Artigo em Inglês | MEDLINE | ID: mdl-28504713

RESUMO

The proto-oncogene PTTG and its binding partner PBF have been widely studied in multiple cancer types, particularly thyroid and colorectal, but their combined role in tumourigenesis is uncharacterised. Here, we show for the first time that together PTTG and PBF significantly modulate DNA damage response (DDR) genes, including p53 target genes, required to maintain genomic integrity in thyroid cells. Critically, DDR genes were extensively repressed in primary thyrocytes from a bitransgenic murine model (Bi-Tg) of thyroid-specific PBF and PTTG overexpression. Irradiation exposure to amplify p53 levels further induced significant repression of DDR genes in Bi-Tg thyrocytes (P=2.4 × 10-4) compared with either PBF- (P=1.5 × 10-3) or PTTG-expressing thyrocytes (P=NS). Consistent with this, genetic instability was greatest in Bi-Tg thyrocytes with a mean genetic instability (GI) index of 35.8±2.6%, as well as significant induction of gross chromosomal aberrations in thyroidal TPC-1 cells following overexpression of PBF and PTTG. We extended our findings to human thyroid cancer using TCGA data sets (n=322) and found striking correlations with PBF and PTTG expression in well-characterised DDR gene panel RNA-seq data. In addition, genetic associations and transient transfection identified PBF as a downstream target of the receptor tyrosine kinase-BRAF signalling pathway, emphasising a role for PBF as a novel component in a pathway well described to drive neoplastic growth. We also showed that overall survival (P=1.91 × 10-5) and disease-free survival (P=4.9 × 10-5) was poorer for TCGA patients with elevated tumoural PBF/PTTG expression and mutationally activated BRAF. Together our findings indicate that PBF and PTTG have a critical role in promoting thyroid cancer that is predictive of poorer patient outcome.


Assuntos
Dano ao DNA , Proteínas de Membrana/metabolismo , Securina/metabolismo , Neoplasias da Glândula Tireoide/genética , Neoplasias da Glândula Tireoide/metabolismo , Animais , Modelos Animais de Doenças , Feminino , Humanos , Peptídeos e Proteínas de Sinalização Intracelular , Masculino , Proteínas de Membrana/genética , Camundongos , Camundongos Transgênicos , Prognóstico , Proto-Oncogene Mas , Securina/genética , Taxa de Sobrevida , Neoplasias da Glândula Tireoide/patologia , Transfecção , Resultado do Tratamento
18.
Patient Saf Surg ; 11: 10, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28396695

RESUMO

BACKGROUND: Approximately 12% of all ureteral stents placed are retained or "forgotten." Forgotten stents are associated with significant safety concerns as well as increased costs and legal issues. Retained ureteral stents (RUS) often occur due to lack of clinical follow-up, communication or language barriers, and economic concerns. METHODS: We describe a multiplatform application that facilitates data collection to prevent RUS. The "Stent Tracker" application can be installed on mobile devices and computers. The encrypted and password-protected information is accessible from any device and provides information about each procedure, stent placement and removal dates, as well as product description. This multicenter retrospective study included 194 patients who underwent stent placement between July and October 2015. Nominal data was tallied and ordinal data was divided into quartiles of 25, 50, and 75%. RESULTS: A total of 194 patients from three institutions underwent ureteral stent placement. Reasons for stent placement include 122 cases post ureteroscopy (63%), 8 cases post percutaneous nephrolithotomy (PCNL) (4%), 14 cases post extracorporeal shock wave lithotripsy (SWL) (7%), 18 cases of cancer-related ureteral obstruction (9%), 21 cases of hydronephrosis (11%), and 11 for other reasons (6%). Of these patients, only one patient was lost to follow-up (0.5%). On average, ureteral stents were removed within 14 days of placement (IQR: 8-26 days). CONCLUSIONS: The "Stent Tracker" is a patient safety application that provides a secure and simplified interface, which can significantly reduce the incidence of RUS. Further developments could include automated notifications to patients and staff, color-coding, and integrated information with electronic patient charts.

19.
Int. braz. j. urol ; 43(2): 289-303, Mar.-Apr. 2017. tab, graf
Artigo em Inglês | LILACS | ID: biblio-840832

RESUMO

ABSTRACT Objectives We sought to determine whether disease representation in the Cochrane Database of Systematic Reviews (CDSR) reflects disease burden, measured by the Global Burden of Disease (GBD) Study as disability-adjusted life-years (DALYs). Materials and Methods Two investigators performed independent assessment of ten men’s health and urologic diseases (MHUDs) in CDSR for systematic review and protocol representation, which were compared with percentage of total 2010 DALYs for the ten conditions. Data were analyzed for correlation using Spearman rank analysis. Results Nine of ten MHUDs were represented by at least one CDSR review. There was a poor and statistically insignificant positive correlation between CDSR representation and disease burden (rho = 0.42, p = 0.23). CDSR representation was aligned with disease burden for three conditions, greater than disease burden for one condition, and less than disease burden for six conditions. Conclusions These results yield high-quality estimates to inform future research prioritization for MHUDs. While prioritization processes are complex and multi-faceted, disease burden should be strongly considered. Awareness of research priority setting has the potential to minimize research disparities on a global scale.


Assuntos
Humanos , Masculino , Doenças Urológicas , Literatura de Revisão como Assunto , Pesquisa Biomédica/tendências , Pesquisa Biomédica/estatística & dados numéricos , Saúde do Homem/tendências , Saúde do Homem/estatística & dados numéricos , Fatores de Tempo , Neoplasias Urológicas , Estatísticas não Paramétricas , Anos de Vida Ajustados por Qualidade de Vida , Carga Global da Doença , Infertilidade Masculina
20.
J Small Anim Pract ; 58(2): 109-114, 2017 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-28160306

RESUMO

OBJECTIVE: To assess diagnostic efficacy of a modified tibial compression test in predicting medial meniscal injury in dogs with cranial cruciate ligament failure. METHODS: Dogs admitted for surgical stabilisation of stifles with cranial cruciate ligament failure were examined by five preoperative physical tests to assess medial meniscal injury. Results of each physical test were compared with findings at arthrotomy and used to calculate sensitivities, specificities, positive and negative predictive values. RESULTS: None of the physical tests were accurate in reflecting meniscal integrity for dogs with cranial cruciate failure. Out of the five tests, the modified tibial compression test exhibited the highest concordance and sensitivity for the detection of medial meniscal tears. A palpable click during the modified tibial compression test had a sensitivity and specificity up to 63 and 77%, respectively, for the detection of medial meniscal lesions. Concordance values were up to 40% for the modified tibial compression test, followed by the range of motion test (up to 25%), while all other physical tests had concordance values below 10%. CLINICAL SIGNIFICANCE: Physical tests are highly available, affordable and can be easily performed, but their efficacy in diagnosing medical meniscal injury is low. Meniscal clicks associated with meniscal tears were more frequently elicited during the modified tibial compression test when compared with other traditional tests.


Assuntos
Lesões do Ligamento Cruzado Anterior/veterinária , Cães/lesões , Lesões do Menisco Tibial/veterinária , Animais , Lesões do Ligamento Cruzado Anterior/diagnóstico , Feminino , Masculino , Sensibilidade e Especificidade , Joelho de Quadrúpedes/lesões , Lesões do Menisco Tibial/diagnóstico
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