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1.
Front Cell Dev Biol ; 12: 1344070, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38440076

RESUMO

The lymphatic vasculature regulates lung homeostasis through drainage of fluid and trafficking of immune cells and plays a key role in the response to lung injury in several disease states. We have previously shown that lymphatic dysfunction occurs early in the pathogenesis of chronic obstructive pulmonary disease (COPD) caused by cigarette smoke (CS) and that this is associated with increased thrombin and fibrin clots in lung lymph. However, the direct effects of CS and thrombin on lymphatic endothelial cells (LECs) in COPD are not entirely clear. Studies of the blood vasculature have shown that COPD is associated with increased thrombin after CS exposure that causes endothelial dysfunction characterized by changes in the expression of coagulation factors and leukocyte adhesion proteins. Here, we determined whether similar changes occur in LECs. We used an in vitro cell culture system and treated human lung microvascular lymphatic endothelial cells with cigarette smoke extract (CSE) and/or thrombin. We found that CSE treatment led to decreased fibrinolytic activity in LECs, which was associated with increased expression of plasminogen activator inhibitor 1 (PAI-1). LECs treated with both CSE and thrombin together had a decreased expression of tissue factor pathway inhibitor (TFPI) and increased expression of adhesion molecules. RNA sequencing of lung LECs isolated from mice exposed to CS also showed upregulation of prothrombotic and inflammatory pathways at both acute and chronic exposure time points. Analysis of publicly available single-cell RNA sequencing of LECs as well as immunohistochemical staining of lung tissue from COPD patients supported these data and showed increased expression of inflammatory markers in LECs from COPD patients compared to those from controls. These studies suggest that in parallel with blood vessels, the lymphatic endothelium undergoes inflammatory changes associated with CS exposure and increased thrombin in COPD. Further research is needed to unravel the mechanisms by which these changes affect lymphatic function and drive tissue injury in COPD.

2.
bioRxiv ; 2023 Nov 02.
Artigo em Inglês | MEDLINE | ID: mdl-37961242

RESUMO

Chronic Obstructive Pulmonary Disease (COPD) is a heterogeneous disease that is characterized by many clinical phenotypes. One such phenotype of COPD is defined by emphysema, pathogenic lung tertiary lymphoid organs (TLOs), and autoantibody production. We have previously shown that lymphatic dysfunction can cause lung TLO formation and lung injury in mice. We now sought to uncover whether underlying lymphatic dysfunction may be a driver of lung injury in cigarette smoke (CS)-induced COPD. We found that lung TLOs in mice with lymphatic dysfunction produce autoantibodies and are associated with a lymphatic endothelial cell subtype that expresses antigen presentation genes. Mice with underlying lymphatic dysfunction develop increased emphysema after CS exposure, with increased size and activation of TLOs. CS further increased autoantibody production in mice with lymphatic dysfunction. B-cell blockade prevented TLO formation and decreased lung injury after CS in mice with lymphatic dysfunction. Using tissue from human COPD patients, we also found evidence of a lymphatic gene signature that was specific to patients with emphysema and prominent TLOs compared to COPD patients without emphysema. Taken together, these data suggest that lymphatic dysfunction may underlie lung injury in a subset of COPD patients with an autoimmune emphysema phenotype.

3.
Risk Anal ; 2023 Sep 24.
Artigo em Inglês | MEDLINE | ID: mdl-37743536

RESUMO

Meteorological services are increasingly moving away from issuing weather warnings based on the exceedance of meteorological thresholds (e.g., windspeed), toward risk-based (or "impact-based") approaches. The UK Met Office's National Severe Weather Warning Service has been a pioneer of this approach, issuing yellow, amber, and red warnings based on an integrated evaluation of information about the likelihood of occurrence and potential impact severity. However, although this approach is inherently probabilistic, probabilistic information does not currently accompany public weather warning communications. In this study, we explored whether providing information about the likelihood and impact severity of forecast weather affected subjective judgments of likelihood, severity, concern, trust in forecast, and intention to take protective action. In a mixed-factorial online experiment, 550 UK residents from 2 regions with different weather profiles were randomly assigned to 1 of 3 Warning Format conditions (Color-only, Text, Risk Matrix) and presented with 3 warnings: high-probability/moderate-impact (amber HPMI); low-probability/high-impact (amber); high-probability/high-impact (red). Amongst those presented with information about probability and impact severity, red high-likelihood/high-impact warnings elicited the strongest ratings on all dependent variables, followed by amber HPMI warnings. Amber low-likelihood/high-impact warnings elicited the lowest perceived likelihood, severity, concern, trust, and intention to take protective responses. Taken together, this indicates that UK residents are sensitive to probabilistic information for amber warnings, and that communicating that severe events are unlikely to occur reduces perceived risk, trust in the warning, and behavioral intention, even though potential impacts could be severe. We discuss the practical implications of this for weather warning communication.

4.
Sci Rep ; 12(1): 5012, 2022 03 23.
Artigo em Inglês | MEDLINE | ID: mdl-35322079

RESUMO

The lymphatic vasculature is critical for lung function, but defects in lymphatic function in the pathogenesis of lung disease is understudied. In mice, lymphatic dysfunction alone is sufficient to cause lung injury that resembles human emphysema. Whether lymphatic function is disrupted in cigarette smoke (CS)-induced emphysema is unknown. In this study, we investigated the effect of CS on lung lymphatic function. Analysis of human lung tissue revealed significant lung lymphatic thrombosis in patients with emphysema compared to control smokers that increased with disease severity. In a mouse model, CS exposure led to lung lymphatic thrombosis, decreased lymphatic drainage, and impaired leukocyte trafficking that all preceded the development of emphysema. Proteomic analysis demonstrated an increased abundance of coagulation factors in the lymph draining from the lungs of CS-exposed mice compared to control mice. In addition, in vitro assays demonstrated a direct effect of CS on lymphatic endothelial cell integrity. These data show that CS exposure results in lung lymphatic dysfunction and a shift in thoracic lymph towards a prothrombic state. Furthermore, our data suggest that lymphatic dysfunction is due to effects of CS on the lymphatic vasculature that precede emphysema. These studies demonstrate a novel component of CS-induced lung injury that occurs early in the pathogenesis of emphysema.


Assuntos
Enfisema , Lesão Pulmonar , Enfisema Pulmonar , Fumaça , Trombose , Poluição por Fumaça de Tabaco , Animais , Enfisema/patologia , Humanos , Pulmão/patologia , Lesão Pulmonar/patologia , Camundongos , Camundongos Endogâmicos C57BL , Proteômica , Enfisema Pulmonar/patologia , Fumaça/efeitos adversos , Lesão por Inalação de Fumaça , Trombose/patologia , Nicotiana/efeitos adversos , Poluição por Fumaça de Tabaco/efeitos adversos
5.
Artigo em Inglês | MEDLINE | ID: mdl-34769664

RESUMO

Despite the benefits of the internet and other digital technology, the online world has been associated with a negative impact on university student wellbeing. Many university students report symptoms of pathological internet use. Internationally, further research is needed to understand what student users of technology perceive to be problematic internet and/or digital use. The current study explores the range of perceptions that university students hold about 'digital addiction'. We recruited 33 participants from a UK university into a Q-methodology study. Participants sorted, ranked, and commented on fifty-two statements representing the concourse of 'things written or said about digital addiction'. The statements were identified from a comprehensive search of a wide variety of sources (e.g., newspapers, academic articles, blogs, and YouTube). Principal Component Analysis was used to identify four distinct viewpoints of 'digital addiction': (I) digital addiction is differentiated by the negative consequences experienced by addicted individuals; (II) digital addiction comes from our fascination with the online world; (III) digital addiction is an attempt to escape real world problems and impacts on mental health and relationships; (IV) digital addiction is defined by the amount of time we spend online. All four viewpoints share the perception that people do not realize they are digitally addicted because using and having digital devices on you at all times has become the social norm. There was also overall agreement that that those with 'addictive personalities' were more likely to be 'digitally addicted'. Despite these similarities, complexity and contradictions within the viewpoints surrounding what digital addiction is and how it might be defined are apparent. The information found in this study provides important suggestions of how we might frame prevention and early intervention messages to engage students and ensure they develop the skills necessary to successfully manage their digital lives.


Assuntos
Comportamento Aditivo , Humanos , Internet , Percepção , Estudantes , Reino Unido , Universidades
6.
J Adv Nurs ; 74(7): 1712-1722, 2018 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-29516534

RESUMO

AIMS: This study explored the feasibility of using Construal Level Theory to analyse proxy decision maker thinking about a hypothetical ethical dilemma, relating to a person who has dementia. BACKGROUND: Proxy decision makers make decisions on behalf of individuals who are living with dementia when dementia affects that individual's decision making ability. Ethical dilemmas arise because there is a need to balance the individual's past and contemporary values and views. Understanding of how proxy decision makers respond is incomplete. Construal Level Theory contends that individuals imagine reactions and make predications about the future by crossing psychological distance. This involves abstract thinking, giving meaning to decisions. There is no empirical evidence of Construal Level Theory being used to analyse proxy decision maker thinking. Exploring the feasibility of using Construal Level Theory to understand dementia carer thinking regarding proxy decisions may provide insights which inform the support given. DESIGN: Descriptive qualitative research with semi-structured interviews. METHODS: Seven participants were interviewed using a hypothetical dementia care scenario in February 2016. Interview transcripts were analysed for themes. Construal Level Theory was applied to analyse participant responses within themes using the Linguistic Category Model. RESULTS: Participants travelled across psychological distance, using abstract thinking to clarify goals and provide a basis for decisions. When thinking concretely participants established boundaries regarding the ethical dilemma. CONCLUSION: Construal Level Theory gives insight into proxy decision maker thinking and the levels of abstraction used. Understanding what dementia carers think about when making proxy decisions may help nurses to understand their perspectives and to provide appropriate support.


Assuntos
Cuidadores/ética , Tomada de Decisão Clínica/ética , Demência/terapia , Procurador , Adulto , Idoso , Cuidadores/psicologia , Estudos de Viabilidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pensamento , Consentimento do Representante Legal/ética , Adulto Jovem
7.
J Nurs Adm ; 47(7-8): 384-390, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28727624

RESUMO

Nurse residency programs are widely implemented to enhance integration of new graduate nurses entering the workforce. This article presents a retrospective analysis of 10 years of residency data from an internally developed residency program that used the Casey-Fink Graduate Nurse Experience Survey. Outcomes of this program were similar to those from studies using commercially available products, suggesting that an internally developed residency curricula may be equally beneficial to the development of new graduate nurses.


Assuntos
Bacharelado em Enfermagem/organização & administração , Internato não Médico/organização & administração , Internato não Médico/estatística & dados numéricos , Recursos Humanos de Enfermagem Hospitalar/educação , Recursos Humanos de Enfermagem Hospitalar/estatística & dados numéricos , Inovação Organizacional/economia , Adulto , Feminino , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Desenvolvimento de Programas , Avaliação de Programas e Projetos de Saúde , Estudos Retrospectivos , Inquéritos e Questionários , Estados Unidos
8.
Soc Sci Med ; 161: 83-91, 2016 07.
Artigo em Inglês | MEDLINE | ID: mdl-27261532

RESUMO

BACKGROUND: Research governance requires patients give informed consent to participate in clinical trials. However, there are concerns that consent information may not support patient participation decisions. This study investigates the utility of consent information in supporting women's trial participation decisions when receiving treatment for cancer. DESIGN: An interview study with women receiving cancer treatments at a medical oncology outpatient clinic in Yorkshire (UK). All women over 18 years, not admitted to a hospital ward and who had currently or previously been invited to take part in a trial were invited to take part in the study over a three month period. Interviews were audio-tape recorded, transcribed and analysed using thematic analysis. RESULTS: Of those eligible (n = 41), 21 women with breast (n = 11), ovarian (n = 8) and endometrial (n = 2) cancer participated (mean age = 57 years). Eighteen had made at least one trial decision and three were considering taking part in a trial. Findings are synthesised under two analytical themes: 1) Influence of the cancer and cancer treatment context on decision making for trial participation; and 2) Experiences of the consenting process and their influence on decision making. CONCLUSIONS: Designing trial information to represent explicitly the trial participation decision as being between standard care and study-related care options is more likely to effectively support patients in making informed decisions between standard care treatments and taking part in a trial.


Assuntos
Consentimento Livre e Esclarecido/normas , Neoplasias/psicologia , Participação do Paciente/métodos , Seleção de Pacientes/ética , Adulto , Idoso , Idoso de 80 Anos ou mais , Instituições de Assistência Ambulatorial/organização & administração , Estudos Transversais , Técnicas de Apoio para a Decisão , Feminino , Humanos , Consentimento Livre e Esclarecido/psicologia , Pessoa de Meia-Idade , Neoplasias/terapia , Participação do Paciente/psicologia , Pesquisa Qualitativa , Inquéritos e Questionários , Reino Unido
9.
Cancer Nurs ; 39(4): E51-60, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-26390074

RESUMO

BACKGROUND: Expressive writing has been shown to improve quality of life, fatigue, and posttraumatic stress among breast cancer patients across cultures. Understanding how and why the method may be beneficial to patients can increase awareness of the psychosocial impact of breast cancer and enhance interventional work within this population. Qualitative research on experiential aspects of interventions may inform the theoretical understanding and generate hypotheses for future studies. AIM: The aim of the study was to explore and describe the experience and feasibility of expressive writing among women with breast cancer following mastectomy and immediate or delayed reconstructive surgery. METHODS: Seven participants enrolled to undertake 4 episodes of expressive writing at home, with semistructured interviews conducted afterward and analyzed using experiential thematic analysis. RESULTS: Three themes emerged through analysis: writing as process, writing as therapeutic, and writing as a means to help others. CONCLUSIONS: Findings illuminate experiential variations in expressive writing and how storytelling encourages a release of cognitive and emotional strains, surrendering these to reside in the text. The method was said to process feelings and capture experiences tied to a new and overwhelming illness situation, as impressions became expressions through writing. Expressive writing, therefore, is a valuable tool for healthcare providers to introduce into the plan of care for patients with breast cancer and potentially other cancer patient groups. IMPLICATIONS FOR PRACTICE: This study augments existing evidence to support the appropriateness of expressive writing as an intervention after a breast cancer diagnosis. Further studies should evaluate its feasibility at different time points in survivorship.


Assuntos
Neoplasias da Mama/psicologia , Emoções , Qualidade de Vida/psicologia , Redação , Adulto , Idoso , Feminino , Humanos , Pessoa de Meia-Idade , Noruega , Sudoeste dos Estados Unidos , Estresse Psicológico/terapia , Sobreviventes/psicologia
10.
J Nurs Adm ; 45(4): 218-25, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-25803804

RESUMO

This quality improvement project evaluated the accuracy of harm scores entered into an event reporting system by inpatient nursing staff at a National Cancer Institute-designated comprehensive cancer center. Nurses scored 10 safety scenarios using 2 versions of the Agency for Healthcare Research and Quality scale to determine interrater reliability. Results indicated inconsistency in the way nurses scored the scenarios, suggesting that the event reporting system may not accurately portray the severity of harm in patient safety events. Nurse executives can use this information to guide the development and implementation of incident reporting systems.


Assuntos
Redução do Dano , Erros Médicos/prevenção & controle , Segurança do Paciente , Melhoria de Qualidade , Adolescente , Adulto , Feminino , Humanos , Liderança , Masculino , Erros Médicos/estatística & dados numéricos , Pessoa de Meia-Idade , Neoplasias/terapia , Reprodutibilidade dos Testes
11.
HERD ; 8(2): 56-70, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25816381

RESUMO

OBJECTIVE: The objective of the study was to examine the impact of decentralization on operational efficiency, staff well-being, and teamwork on three inpatient units. BACKGROUND: Decentralized unit operations and the corresponding physical design solution were hypothesized to positively affect several concerns-productive use of nursing time, staff stress, walking distances, and teamwork, among others. With a wide adoption of the concept, empirical evidence on the impact of decentralization was warranted. METHODS: A multimethod, before-and-after, quasi-experimental design was adopted for the study, focusing on five issues, namely, (1) how nurses spend their time, (2) walking distance, (3) acute stress, (4) productivity, and (5) teamwork. Data on all five issues were collected on three older units with centralized operational model (before move). The same set of data, with identical tools and measures, were collected on the same units after move in to new physical units with decentralized operational model. Data were collected during spring and fall of 2011. RESULTS: Documentation, nurse station use, medication room use, and supplies room use showed consistent change across the three units. Walking distance increased (statistically significant) on two of the three units. Self-reported level of collaboration decreased, although assessment of the physical facility for collaboration increased. CONCLUSIONS: Decentralized nursing and physical design models potentially result in quality of work improvements associated with documentation, medication, and supplies. However, there are unexpected consequences associated with walking, and staff collaboration and teamwork. The solution to the unexpected consequences may lie in operational interventions and greater emphasis on culture change.


Assuntos
Ergonomia , Unidades Hospitalares/organização & administração , Decoração de Interiores e Mobiliário , Satisfação no Emprego , Recursos Humanos de Enfermagem Hospitalar/organização & administração , Postos de Enfermagem/organização & administração , Saúde Ocupacional , Equipe de Assistência ao Paciente/organização & administração , Eficiência Organizacional , Feminino , Humanos , Relações Interprofissionais , Masculino , Recursos Humanos de Enfermagem Hospitalar/psicologia , Fatores de Tempo , Caminhada/estatística & dados numéricos
12.
J Nurs Adm ; 45(3): 165-71, 2015 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-25689503

RESUMO

To ensure a well-prepared advanced practice oncology nursing workforce, we developed a unique yearlong fellowship promoting expertise in cancer care and focusing on the development of in-depth knowledge and evidence-based clinical oncology practice. This article describes the process for developing and implementing the fellowship and its components, outcomes, and attributes for success.


Assuntos
Prática Avançada de Enfermagem/educação , Bolsas de Estudo , Enfermagem Oncológica/educação , Avaliação de Processos e Resultados em Cuidados de Saúde , Humanos , Modelos de Enfermagem , Texas
13.
Cancer Nurs ; 38(4): 260-9, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25232959

RESUMO

BACKGROUND: Cancer is the leading cause of nonaccidental morbidity and mortality among young adults (YAs) in the United States. Stem cell transplantation (SCT), a treatment modality for a variety of YA malignancies, often requires prolonged hospitalization and immune-compromising treatment regimens. Stem cell transplantation may isolate YAs physically and emotionally, contributing to uncertainty about treatment processes, outcomes, and long-term sequelae. Studies in this population suggest that uncertainty can contribute to difficulty accomplishing basic developmental tasks. Few studies have examined the experiences of YAs in active cancer treatment, particularly those undergoing SCT. OBJECTIVES: This study explored the cancer experiences of YAs aged 18 to 25 years leading up to SCT and explored how YAs construct issues of uncertainty related to the transplantation experience. METHODS: Interviews with 14 YAs conducted within 24 hours of admission to undergo SCT were analyzed using thematic analysis from a medical ethnographic perspective. RESULTS: Themes emerged within 2 domains: relational and psychoemotional. The relational theme of "altered relationships" included the subthemes of "moving from" and "moving toward." The psychoemotional theme of the "power of perspective" included the subthemes of "optimism," "acknowledgment of death," "informational empowerment," and "developing a new outlook." CONCLUSIONS: Our findings offer new insights into the YA experience in the context of active cancer treatment, specifically how the cancer experience impacts relationships and how this experience is influenced by YAs' perspectives. IMPLICATIONS FOR PRACTICE: This study provides a foundation for addressing the psychosocial needs of YAs hospitalized for SCT, paying particular attention to the development of specific interventions.


Assuntos
Neoplasias/mortalidade , Neoplasias/psicologia , Transplante de Células-Tronco/psicologia , Sobreviventes/psicologia , Adolescente , Atitude Frente a Saúde , Feminino , Humanos , Masculino , Neoplasias/complicações , Pesquisa Qualitativa , Estados Unidos , Adulto Jovem
14.
Ann Surg ; 261(6): 1114-23, 2015 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-25243545

RESUMO

OBJECTIVE: To evaluate the effects of a fast-track esophagectomy protocol (FTEP) on esophageal cancer patients' safety, length of hospital stay (LOS), and hospital charges. BACKGROUND: FTEP involved transferring patients to the telemetry unit instead of the surgical intensive care unit (SICU) after esophagectomy. METHODS: We retrospectively reviewed 708 consecutive patients who underwent esophagectomy for primary esophageal cancer during the 4 years before (group A; 322 patients) or 4 years after (group B; 386 patients) the institution of an FTEP. Postoperative morbidity and mortality, LOS, and hospital charges were reviewed. RESULTS: Compared with group A, group B had significantly shorter median LOS (12 days vs 8 days; P < 0.001); lower mean numbers of SICU days (4.5 days vs 1.2 days; P < 0.001) and telemetry days (12.7 days vs 9.7 days; P < 0.001); and lower rates of atrial arrhythmia (27% vs 19%; P = 0.013) and pulmonary complications (27% vs 20%; P = 0.016). Multivariable analysis revealed FTEP to be associated with shorter LOS (P < 0.001) even after adjustment for predictors like tumor histology and location. FTEP was also associated with a lower rate of pulmonary complications (odds ratio = 0.655; 95% confidence interval = 0.456, 0.942; P = 0.022). In addition, the median hospital charges associated with primary admission and readmission within 90 days for group B ($65,649) were lower than that for group A ($79,117; P < 0.001). CONCLUSIONS: These findings suggest that an FTEP reduces patients' LOS, perioperative morbidity, and hospital charges.


Assuntos
Adenocarcinoma/cirurgia , Carcinoma de Células Escamosas/cirurgia , Neoplasias Esofágicas/cirurgia , Esofagectomia , Preços Hospitalares , Cuidados Pós-Operatórios/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Protocolos Clínicos , Esofagectomia/economia , Esofagectomia/mortalidade , Esofagectomia/estatística & dados numéricos , Feminino , Humanos , Unidades de Terapia Intensiva , Tempo de Internação , Masculino , Pessoa de Meia-Idade , Morbidade , Segurança do Paciente/economia , Segurança do Paciente/normas , Cuidados Pós-Operatórios/economia , Estudos Retrospectivos , Telemetria , Resultado do Tratamento , Adulto Jovem
15.
Med Decis Making ; 35(1): 22-6, 2015 01.
Artigo em Inglês | MEDLINE | ID: mdl-25035261

RESUMO

BACKGROUND: Numeracy refers to people's ability to use numbers. Low numeracy has been associated with difficulties in understanding risk-benefit information and making health decisions. Older adults tend to perform worse than younger adults on measures of numeracy, but some theories of aging suggest that older adults may lack motivation for such tasks. We therefore test whether age differences in numeracy performance are mediated by a reduced motivation to think hard about complex problems-as measured by need for cognition. METHOD: We recruited an age-diverse convenience sample of 306 UK adults. They completed measures of numeracy and need for cognition. They self-reported their educational attainment and other demographics. RESULTS: Older age was related to lower numeracy and lower need for cognition. The negative relationship between age and numeracy was mediated by need for cognition. These findings held after we controlled for educational attainment and other demographic factors. DISCUSSION: Older adults may show lower numeracy performance due to lack of motivation. We discuss strategies for improving people's motivation to complete numeracy measures and other numerical tasks.


Assuntos
Cognição , Matemática , Motivação , Adolescente , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Tomada de Decisões , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fatores Socioeconômicos , Reino Unido , Adulto Jovem
16.
Med Decis Making ; 34(5): 567-82, 2014 07.
Artigo em Inglês | MEDLINE | ID: mdl-24732048

RESUMO

OBJECTIVE: Health professionals must enable patients to make informed decisions about health care choices through unbiased presentation of all options. This study examined whether presenting the decision as "opportunity" rather than "choice" biased individuals' preferences in the context of trial participation for cancer treatment. METHODS: Self-selecting healthy women (N = 124) were randomly assigned to the following decision frames: opportunity to take part in the trial (opt-in), opportunity to be removed from the trial (opt-out), and choice to have standard treatment or take part in the trial (choice). The computer-based task required women to make a hypothetical choice about a real-world cancer treatment trial. The software presented the framed scenario, recorded initial preference, presented comprehensive and balanced information, traced participants' use of information during decision making, and recorded final decision. A posttask paper questionnaire assessed perceived risk, attitudes, subjective norm, perceived behavioral control, and satisfaction with decision. RESULTS: Framing influenced women's immediate preferences. Opportunity frames, whether opt-in or opt-out, introduced a bias as they discouraged women from choosing standard treatment. Using the choice frame avoided this bias. The opt-out opportunity frame also affected women's perceived social norm; women felt that others endorsed the trial option. The framing bias was not present once participants had had the opportunity to view detailed information on the options within a patient decision aid format. There were no group differences in information acquisition and final decisions. Sixteen percent changed their initial preference after receiving full information. CONCLUSIONS: A "choice" frame, where all treatment options are explicit, is less likely to bias preferences. Presentation of full information in parallel, option-by-attribute format is likely to "de-bias" the decision frame. Tailoring of information to initial preferences would be ill-advised as preferences may change following detailed information.


Assuntos
Tomada de Decisões , Técnicas de Apoio para a Decisão , Adolescente , Adulto , Atitude , Comportamento de Escolha , Feminino , Humanos , Pessoa de Meia-Idade , Participação do Paciente , Preferência do Paciente , Satisfação do Paciente , Medição de Risco , Adulto Jovem
17.
Am J Physiol Heart Circ Physiol ; 305(5): H687-98, 2013 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-23792683

RESUMO

Protein 3-nitrotyrosine (3-NT) formation is frequently regarded as a simple biomarker of disease, an irreversible posttranslational modification that can disrupt protein structure and function. Nevertheless, evidence that protein 3-NT modifications may be site selective and reversible, thus allowing for physiological regulation of protein activity, has begun to emerge. We have previously reported that cyclooxygenase (COX)-1 undergoes heme-dependent nitration of Tyr(385), an internal and catalytically essential residue. In the present study, we demonstrate that nitrated COX-1 undergoes a rapid reversal of nitration by substrate-selective and biologically regulated denitrase activity. Using nitrated COX-1 as a substrate, denitrase activity was validated and quantified by analytic HPLC with electrochemical detection and determined to be constitutively active in murine and human endothelial cells, macrophages, and a variety of tissue samples. Smooth muscle cells, however, contained little denitrase activity. Further characterizing this denitrase activity, we found that it was inhibited by free 3-NT and may be enhanced by endogenous nitric oxide and exogenously administered carbon monoxide. Finally, we describe a purification protocol that results in significant enrichment of a discrete denitrase-containing fraction, which maintains activity throughout the purification process. These findings reveal that nitrated COX-1 is a substrate for a denitrase in cells and tissues, implying that the reciprocal processes of nitration and denitration may modulate bioactive lipid synthesis in the setting of inflammation. In addition, our data reveal that denitration is a controlled process that may have broad importance for regulating cell signaling events in nitric oxide-generating systems during oxidative/nitrosative stress.


Assuntos
Ciclo-Oxigenase 1/metabolismo , Endotélio Vascular/metabolismo , Macrófagos/metabolismo , Músculo Liso Vascular/metabolismo , Nitratos/metabolismo , Oxirredutases/metabolismo , Adaptação Fisiológica/fisiologia , Animais , Linhagem Celular , Células Cultivadas , Endotélio Vascular/citologia , Humanos , Macrófagos/citologia , Camundongos , Camundongos Endogâmicos C57BL , Modelos Animais , Músculo Liso Vascular/citologia , Óxido Nítrico/metabolismo , Óxido Nítrico Sintase/metabolismo , Estresse Oxidativo/fisiologia , Ratos , Tirosina/análogos & derivados , Tirosina/metabolismo
18.
DNA Cell Biol ; 32(4): 206-18, 2013 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-23570576

RESUMO

Pulmonary fibrosis is characterized by an inflammatory response that includes macrophages, neutrophils, lymphocytes, and mast cells. The purpose of this study was to evaluate whether mast cells play a role in initiating pulmonary fibrosis. Pulmonary fibrosis was induced with bleomycin in mast-cell-deficient WBB6F1-W/W(v) (MCD) mice and their congenic controls (WBB6F1-(+)/(+)). Mast cell deficiency protected against bleomycin-induced pulmonary fibrosis, but protection was reversed with the re-introduction of mast cells to the lungs of MCD mice. Two mast cell mediators were identified as fibrogenic: histamine and renin, via angiotensin (ANG II). Both human and rat lung fibroblasts express the histamine H1 and ANG II AT1 receptor subtypes and when activated, they promote proliferation, transforming growth factor ß1 secretion, and collagen synthesis. Mast cells appear to be critical to pulmonary fibrosis. Therapeutic blockade of mast cell degranulation and/or histamine and ANG II receptors should attenuate pulmonary fibrosis.


Assuntos
Antibióticos Antineoplásicos/toxicidade , Bleomicina/toxicidade , Proliferação de Células/efeitos dos fármacos , Fibroblastos/patologia , Pulmão/patologia , Mastócitos/fisiologia , Fibrose Pulmonar/patologia , Angiotensina II/metabolismo , Animais , Western Blotting , Colágeno/metabolismo , Ensaio de Imunoadsorção Enzimática , Fibroblastos/efeitos dos fármacos , Fibroblastos/metabolismo , Histamina/metabolismo , Humanos , Técnicas Imunoenzimáticas , Pulmão/efeitos dos fármacos , Pulmão/metabolismo , Masculino , Mastócitos/citologia , Mastócitos/efeitos dos fármacos , Camundongos , Camundongos Knockout , Fibrose Pulmonar/induzido quimicamente , Fibrose Pulmonar/tratamento farmacológico , Radioimunoensaio , Ratos , Receptor Tipo 1 de Angiotensina/metabolismo , Renina/metabolismo , Fator de Crescimento Transformador beta1/metabolismo
19.
Cancer ; 118(10): 2571-82, 2012 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-22045610

RESUMO

Responding to growing concerns regarding the safety, quality, and efficacy of cancer care in the United States, the Institute of Medicine (IOM) of the National Academy of Sciences commissioned a comprehensive review of cancer care delivery in the US health care system in the late 1990s. The National Cancer Policy Board (NCPB), a 20-member board with broad representation, performed this review. In its review, the NCPB focused on the state of cancer care delivery at that time, its shortcomings, and ways to measure and improve the quality of cancer care. The NCPB described an ideal cancer care system in which patients would have equitable access to coordinated, guideline-based care and novel therapies throughout the course of their disease. In 1999, the IOM published the results of this review in its influential report, Ensuring Quality Cancer Care. The report outlined 10 recommendations, which, when implemented, would: 1) improve the quality of cancer care, 2) increase the current understanding of quality cancer care, and 3) reduce or eliminate access barriers to quality cancer care. Despite the fervor generated by this report, there are lingering doubts regarding the safety and quality of cancer care in the United States today. Increased awareness of medical errors and barriers to quality care, coupled with escalating health care costs, has prompted national efforts to reform the health care system. These efforts by health care providers and policymakers should bridge the gap between the ideal state described in Ensuring Quality Cancer Care and the current state of cancer care in the United States.


Assuntos
Neoplasias/terapia , Qualidade da Assistência à Saúde , Benchmarking , Seguimentos , Custos de Cuidados de Saúde , Acessibilidade aos Serviços de Saúde , Humanos , Educação de Pacientes como Assunto
20.
Health Expect ; 14 Suppl 1: 20-32, 2011 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-20629765

RESUMO

BACKGROUND: Decision aids help patients make informed treatment decisions. Values clarification (VC) techniques are part of decision aids that help patients assimilate the information with their personal values. There is little evidence that these techniques contribute to enhanced decision making over and above the provision of good quality information. OBJECTIVES: To assess whether VC techniques are active ingredients in enhancing informed decision making and explain how and why they work. METHODS: Participants were randomly assigned to one of three groups: (i) information only, (ii) information plus implicit task, (iii) information plus explicit task. Thirty healthy women from a UK University participated by making a hypothetical choice between taking part in a clinical trial and having the standard treatment for breast cancer. Verbal protocols were elicited by think-aloud method and content analysed to assess informed decision making; a questionnaire was completed after the decision assessing decision preference, perceptions of decisional conflict and ambivalence. Data were analysed using multivariate statistics. FINDINGS: No participants changed their decision preference as a result of the VC techniques. Women in the explicit VC group evaluated more information in accord with personal values, expressed lower ambivalence, decisional uncertainty and greater clarity of personal values than those in the implicit VC and control groups. Feelings of ambivalence about both options were related to decisional conflict. CONCLUSION: Explicit VC techniques are likely to be active ingredients in decision aids. They work by enabling people to deliberate about the decision information in accord with their personal values, which is associated with a better decision experience.


Assuntos
Neoplasias da Mama/terapia , Ensaios Clínicos como Assunto/psicologia , Técnicas de Apoio para a Decisão , Preferência do Paciente , Valores Sociais , Adulto , Feminino , Humanos , Pessoa de Meia-Idade , Educação de Pacientes como Assunto/métodos , Fatores Socioeconômicos , Reino Unido
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