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1.
Respir Care ; 65(3): 347-354, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31796549

RESUMO

BACKGROUND: Individuals with COPD typically experience a gradual deterioration in health, with exacerbations and increased health-care utilization in the years before death. As such, adequate planning of future care is necessary. The objective of this research was to identify gaps in health-care professionals' knowledge related to advance care planning (ACP) for patients with COPD and to prioritize content of future educational interventions for health-care professionals accordingly. METHODS: A modified e-Delphi technique with 2 rounds of rating was used. After a literature review and expert consultation, a multidisciplinary panel developed 40 statements. Statements that did not achieve consensus in round 1 were re-presented in round 2, together with new statements developed after participant feedback. Health-care professionals with expertise in caring for people with COPD were asked to rate the importance of including each of the 40 topics in future educational interventions related to ACP and COPD by using a 5-point Likert scale. Average scores for each topic were calculated and expressed as percentages. Consensus on each topic was achieved if it obtained a score of ≥80%. RESULTS: Thirty-eight health-care professionals were invited to participate, of whom, 21 (55%) took part in both rounds. Consensus was achieved for 32 of 40 statements (80%) in round 1 and for 5 of 10 statements (50%) in round 2. All statements relating to "COPD and palliative care" and "legislation for ACP" achieved consensus after one round. CONCLUSIONS: This study uncovered specific topics that related to ACP and COPD that health-care professionals believe should be included in future educational interventions. In particular, there is a clear need for training that addresses the legal issues surrounding ACP, and information on the best timing and content of ACP discussions with patients with COPD. Such training may enable health-care professionals to incorporate ACP into routine COPD management and, ultimately, improve patient care.


Assuntos
Planejamento Antecipado de Cuidados , Técnica Delphi , Doença Pulmonar Obstrutiva Crônica/terapia , Adulto , Consenso , Feminino , Pessoal de Saúde , Humanos , Masculino , Pessoa de Meia-Idade , Cuidados Paliativos , Inquéritos e Questionários , Adulto Jovem
2.
J Pain Symptom Manage ; 59(6): 1344-1361, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-31837455

RESUMO

CONTEXT: Individuals with chronic obstructive pulmonary disease (COPD) typically experience a gradual worsening of the illness in the years before death. Owing to difficulties in predicting the disease trajectory or the timing of acute exacerbations, advance care planning (ACP) may be of particular importance for individuals with COPD. OBJECTIVES: The objective of this study was to review and summarize the available literature on current practices around ACP in COPD. METHODS: A scoping review of the literature was conducted following the Arksey and O'Malley framework. Original research studies of any design were included. RESULTS: Twenty-eight studies were included. Across studies, there was agreement that ACP should be incorporated into routine COPD management. There was evidence that this does not occur in everyday practice, with conversations tending to focus on day-to-day symptom management. Barriers included prognosis uncertainty, insufficient time and training, and a lack of protocols for who is responsible for initiating ACP. Facilitators included the use of transition points for identifying the appropriate time to initiate ACP, and an increased focus on ACP in professional education. The occurrence of repeated episodes of acute care was identified as a key transition point for identifying the palliative stage of COPD and an appropriate time to initiate ACP. CONCLUSION: The findings of this review confirm agreement among health care professionals and patients with COPD and their carers that ACP should be incorporated into routine COPD management. The use of transition points may help health care professionals overcome the barrier of prognosis uncertainty and identify patients who might benefit from ACP.


Assuntos
Planejamento Antecipado de Cuidados , Doença Pulmonar Obstrutiva Crônica , Comunicação , Pessoal de Saúde , Humanos , Cuidados Paliativos , Doença Pulmonar Obstrutiva Crônica/terapia
3.
BMJ Support Palliat Care ; 4(1): 92-7, 2014 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-24644779

RESUMO

BACKGROUND: The need for undergraduate medical education in palliative care is widely recognised. An optional student-selected module 'Fundamentals of Palliative Medicine' was introduced in 2011 and offered to third-year medical students. The overall objective of the module was to develop students' knowledge, attitudes and skills in palliative care. AIM: To assess impact of the module in terms of qualitative and quantitative measures, and to improve the module design and content for future years. METHODS: Students completed validated tools (Self Efficacy in Palliative Care and Thanatophobia Scale (TS)) premodule and postmodule. A Minute Paper was completed at the penultimate session with students identifying areas they had a good understanding of, and issues they still found unclear. RESULTS: Twenty-four of 155 eligible students chose the module. Significant differences were seen in premodule and postmodule Self Efficacy in Palliative Care scores (communication p<0.0001, patient management p=0.0002 and teamwork p=0.03). No difference was seen in TS score. Five main themes emerged from the qualitative analysis of the Minute Paper: changes to attitudes and knowledge, psychological effects, teaching methods, careers in palliative care, and further palliative care learning needs. Several students commented that the module should be core curriculum. CONCLUSIONS: The module was a popular choice with students, was well received, and appears to have had a significant educational impact in terms of changing students' attitudes and perceived knowledge and skills in palliative care.


Assuntos
Currículo , Educação de Graduação em Medicina/métodos , Medicina Paliativa/educação , Avaliação de Programas e Projetos de Saúde/métodos , Estudantes de Medicina , Humanos , Cuidados Paliativos/métodos , Inquéritos e Questionários
4.
Ann Rheum Dis ; 72(6): 1080-8, 2013 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-23161900

RESUMO

OBJECTIVE: Notch signalling pathways are critical for angiogenesis and endothelial cell (EC) fate; however the mechanisms regulating these processes in the inflamed joint remain to be elucidated. Here, we examine whether Notch signalling mediates vascular endothelial growth factor (VEGF) and angiopoietin 2 (Ang2)-induced vascular function. METHODS: Notch-1 intracellular domain (Notch-1 IC), Notch-4 IC, Delta-like-ligand 4, Hes-related transcriptional repressors-1 and 2 (Hrt-1, Hrt-2) mRNA and/or protein expression was measured by Real-time PCR and/or western blot. VEGF/Ang2 induced EC function was assessed using transwell invasion chambers, matrigel tube formation assays and wound repair scratch assays±Notch-1 siRNA or an γ-secretase inhibitor N-(N-(3,5-Difluorophenacetyl-L-alanly))-S-phenylglycine-t-Butyl Ester (DAPT) in RA synovial explants or human microvascular EC. Interleukin (IL)-6 and IL-8 were measured by ELISA and MMP2 and 9 by gelatine zymography. RESULTS: Notch-1 IC and Notch-4 IC protein expressions were demonstrated in RA and psoriatic arthritis synovial biopsies, with minimal expression observed in Osteoarthritis (OA). VEGF and Ang2 induced Notch-1 IC/ Notch-4 IC protein expression in synovial explant cultures and human microvascular EC levels were further potentiated by VEGF/Ang2 stimulation in combination. Notch-1, Delta-like-ligand 4, and Hrt-2 mRNA expression were significantly induced by VEGF and Ang2 alone and in combination. Furthermore VEGF/Ang2-induced EC invasion, angiogenesis and migration were inhibited by Notch-1 siRNA or DAPT. Conditioned media from VEGF/Ang2 stimulated RA synovial explants induced EC tube formation, an effect that was inhibited by DAPT. Finally, DAPT significantly decreased VEGF/Ang2 induced IL-6, IL-8, MMP2 and 9 expressions in RA synovial explants. CONCLUSIONS: Notch-1 mediates VEGF/Ang2-induced angiogenesis and EC invasion in inflammatory arthritis.


Assuntos
Angiopoietina-2/fisiologia , Artrite Psoriásica/fisiopatologia , Artrite Reumatoide/fisiopatologia , Células Endoteliais/fisiologia , Neovascularização Patológica/fisiopatologia , Osteoartrite/fisiopatologia , Proteínas Proto-Oncogênicas/fisiologia , Receptor Notch1/fisiologia , Receptores Notch/fisiologia , Membrana Sinovial/fisiopatologia , Fator A de Crescimento do Endotélio Vascular/fisiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Proliferação de Células , Feminino , Humanos , Interleucina-6/fisiologia , Interleucina-8/fisiologia , Masculino , Pessoa de Meia-Idade , Receptor Notch4 , Transdução de Sinais
5.
Arthritis Rheum ; 64(7): 2104-13, 2012 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-22275240

RESUMO

OBJECTIVE: To examine the effect of hypoxia on Notch-1 signaling pathway components and angiogenesis in inflammatory arthritis. METHODS: The expression and regulation of Notch-1, its ligand delta-like protein 4 (DLL-4) and downstream signaling components (hairy-related transcription factor 1 [HRT-1], HRT-2), and hypoxia-inducible factor 1α (HIF-1α) under normoxic and hypoxic conditions (1-3%) were assessed in synovial tissue specimens from patients with inflammatory arthritis and controls and in human dermal microvascular endothelial cells (HDMECs) by immunohistology, dual immunofluorescence staining (Notch-1/factor VIII), Western blotting, and real-time polymerase chain reaction. In vivo synovial tissue oxygen levels (tissue PO2) were measured under direct visualization at arthroscopy. HDMEC activation under hypoxic conditions in the presence of Notch-1 small interfering RNA (siRNA), the γ-secretase inhibitor DAPT, or dimethyloxalylglycine (DMOG) was assessed by Matrigel tube formation assay, migration assay, invasion assay, and matrix metalloproteinase 2 (MMP-2)/MMP-9 zymography. RESULTS: Expression of Notch-1, its ligand DLL-4, and HRT-1 was demonstrated in synovial tissue, with the strongest expression localized to perivascular/vascular regions. Localization of Notch-1 to synovial endothelium was confirmed by dual immunofluorescence staining. Notch-1 intracellular domain (NICD) expression was significantly higher in synovial tissue from patients with tissue PO2 of <20 mm Hg (<3% O2) than in those with tissue PO2 of >20 mm Hg (>3% O2). Exposure of HDMECs to 3% hypoxia induced HIF-1α and NICD protein expression and DLL-4, HRT-1, and HRT-2 messenger RNA expression. DMOG directly induced NICD expression, while Notch-1 siRNA inhibited hypoxia-induced HIF-1α expression, suggesting that Notch-1/HIF-1α signaling is bidirectional. Finally, 3% hypoxia-induced angiogenesis, endothelial cell migration, endothelial cell invasion, and proMMP-2 and proMMP-9 activities were inhibited by Notch-1 siRNA and/or the γ-secretase inhibitor DAPT. CONCLUSION: Our findings indicate that Notch-1 is expressed in synovial tissue and that increased NICD expression is associated with low in vivo tissue PO2. Furthermore, Notch-1/HIF-1α interactions mediate hypoxia-induced angiogenesis and invasion in inflammatory arthritis.


Assuntos
Artrite Reumatoide/metabolismo , Hipóxia/metabolismo , Neovascularização Patológica/metabolismo , Receptor Notch1/metabolismo , Membrana Sinovial/metabolismo , Movimento Celular/fisiologia , Células Endoteliais/metabolismo , Feminino , Humanos , Articulação do Joelho/metabolismo , Masculino , Metaloproteinase 2 da Matriz/metabolismo , Metaloproteinase 9 da Matriz/metabolismo , Fator A de Crescimento do Endotélio Vascular/metabolismo
6.
Inflamm Bowel Dis ; 17(8): 1665-73, 2011 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-21287659

RESUMO

BACKGROUND: Intestinal fibroblasts mediate stricture formation in Crohn's disease (CD). Transforming growth factor-ß1 (TGF-ß1) is important in fibroblast activation, while cell attachment and migration is regulated by the adhesion molecule N-cadherin. The aim of this study was to investigate the expression and function of N-cadherin in intestinal fibroblasts in patients with fibrostenosing CD. METHODS: Intestinal fibroblasts were cultured from seromuscular biopsies from patients undergoing resection for terminal ileal fibrostenosing CD (n = 14) or controls patients (n = 8). N-cadherin expression was assessed using Western blot and quantitative reverse-transcription polymerase chain reaction (qRT-PCR). Fibroblasts were stimulated with TGF-ß1 and selective pathway inhibitors Y27632, PD98050, and LY294002 were used to examine the Rho/ROCK, ERK-1/2, and Akt signaling pathways, respectively. Cell migration was assessed using a scratch wound assay. N-cadherin was selectively overexpressed using a plasmid. RESULTS: Fibroblasts from fibrostenosing CD express increased constitutive N-cadherin mRNA and protein and exhibit enhanced basal cell migration relative to those from directly adjacent normal bowel. Control fibroblasts treated with TGF-ß1 induced N-cadherin in a dose-dependent manner which was inhibited by Rho/ROCK and Akt pathway modulation. Control fibroblasts exhibited enhanced cell migration in response to treatment with TGF-ß1 or transfection with an N-cadherin plasmid. CONCLUSIONS: Fibroblasts from strictures in CD express increased constitutive N-cadherin and exhibit enhanced basal cell migration. TGF-ß1 is a potent inducer of N-cadherin in intestinal fibroblasts resulting in enhanced cell migration. The TGF-ß1-mediated induction of N-cadherin may potentiate Crohn's stricture formation.


Assuntos
Caderinas/metabolismo , Doença de Crohn/metabolismo , Doença de Crohn/patologia , Fibroblastos/metabolismo , Íleo/patologia , RNA Mensageiro/metabolismo , Adulto , Análise de Variância , Caderinas/genética , Caderinas/fisiologia , Movimento Celular/fisiologia , Células Cultivadas , Constrição Patológica/metabolismo , Constrição Patológica/patologia , Feminino , Fibroblastos/efeitos dos fármacos , Fibroblastos/fisiologia , Fibrose , Humanos , Masculino , Transdução de Sinais/fisiologia , Fator de Crescimento Transformador beta1/farmacologia , Regulação para Cima/genética
7.
Arterioscler Thromb Vasc Biol ; 29(7): 1112-8, 2009 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-19407245

RESUMO

OBJECTIVE: Notch, VEGF, and components of the Hedgehog (Hh) signaling pathway have been implicated in vascular morphogenesis. The role of Notch in mediating hedgehog control of adult vascular smooth muscle cell (SMC) growth and survival remains unexplored. METHODS AND RESULTS: In cultured SMCs, activation of Hh signaling with recombinant rShh (3.5 mug/mL) or plasmid encoded Shh increased Ptc1 expression, enhanced SMC growth and survival and promoted Hairy-related transcription factor (Hrt) expression while concomitantly increasing VEGF-A levels. These effects were significantly reversed after Hh inhibition with cyclopamine. Shh-induced stimulation of Hrt-3 mRNA and SMC growth and survival was attenuated after inhibition of Notch-mediated CBF-1/RBP-Jk-dependent signaling with RPMS-1 while siRNA knockdown of Hrt-3 inhibited SMC growth and survival. Recombinant VEGF-A increased Hrt-3 mRNA levels while siRNA knockdown abolished rShh stimulated VEGF-A expression while concomitantly inhibiting Shh-induced increases in Hrt-3 mRNA levels, proliferating cell nuclear antigen (PCNA), and Notch 1 IC expression, respectively. Hedgehog components were expressed within intimal SMCs of murine carotid arteries after vascular injury concomitant with a significant increase in mRNA for Ptc1, Gli(2), VEGF-A, Notch 1, and Hrts. CONCLUSIONS: Hedgehog promotes a coordinate regulation of Notch target genes in adult SMCs via VEGF-A.


Assuntos
Artérias Carótidas/metabolismo , Proteínas Hedgehog/fisiologia , Miócitos de Músculo Liso/metabolismo , Receptor Notch1/fisiologia , Fator A de Crescimento do Endotélio Vascular/metabolismo , Animais , Artérias Carótidas/citologia , Linhagem Celular , Regulação da Expressão Gênica , Humanos , Camundongos , Músculo Liso Vascular/metabolismo , RNA Mensageiro/metabolismo , Ratos , Fator A de Crescimento do Endotélio Vascular/genética
8.
Palliat Med ; 21(3): 193-8, 2007 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-17641072

RESUMO

OBJECTIVES: The primary objective in this study is to determine the sensitivity and specificity of a two-item screening interview for depression versus the formal psychiatric interview, in the setting of a specialist palliative in-patient unit so that we may identify those individuals suffering from depressive disorder and therefore optimise their management in this often-complex population. METHODS: A prospective sample of consecutive admissions (n = 167) consented to partake in the study, and the screening interview was asked separately to the formal psychiatric interview. RESULTS: The two-item questionnaire, achieved a sensitivity of 90.7% (95% CI 76.9-97.0) but a lower specificity of 67.7% (95% CI 58.7-75.7). The false positive rate was 32.3% (95% CI 24.3-41.3), but the false negative rate was found to be a low 9.3% (95% CI 3.0-23.1). A subgroup analysis of individuals with a past experience of depressive illness, (n = 95), revealed that a significant number screened positive for depression by the screening test, 55.2% (16/29) compared to those with no background history of depression, 33.3% (22/66) (P = 0.045). CONCLUSION: The high sensitivity and low false negative rate of the two-question screening tool will aid health professionals in identifying depression in the in-patient specialist palliative care unit. Individuals, who admit to a previous experience of depressive illness, are more likely to respond positively to the two-item questionnaire than those who report no prior history of depressive illness (P = 0.045).


Assuntos
Depressão/diagnóstico , Cuidados Paliativos/métodos , Escalas de Graduação Psiquiátrica , Adulto , Idoso , Idoso de 80 Anos ou mais , Distribuição de Qui-Quadrado , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Sensibilidade e Especificidade , Inquéritos e Questionários
9.
Am J Physiol Cell Physiol ; 289(5): C1188-96, 2005 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-15987768

RESUMO

Vascular smooth muscle cell (VSMC) phenotypic modulation is a key factor in vascular pathology. We have investigated the role of Notch receptor signaling in controlling human vascular smooth muscle cell (hVSMC) differentiation in vitro and established a role for cyclic strain-induced changes in Notch signaling in promoting this phenotypic response. The expression of alpha-actin, calponin, myosin, and smoothelin was examined by performing immunocytochemistry, Western blot analysis, and quantitative real-time PCR in hVSMCs cultured under static conditions after forced overexpression of constitutively active Notch 1 and 3 receptors, inhibition of endogenous Cp-binding factor 1 (CBF-1)/recombination signal sequence-binding protein-Jkappa (RBP-Jkappa) signaling, and exposure to cyclic strain using a Flexercell Tension Plus unit. Overexpression of constitutively active Notch intracellular (IC) receptors (Notch 1 IC and Notch 3 IC) resulted in a significant downregulation of alpha-actin, calponin, myosin, and smoothelin expression, an effect that was significantly attenuated after inhibition of Notch-mediated, CBF-1/RBP-Jkappa-dependent signaling by coexpression of RPMS-1 (Epstein-Barr virus-encoded gene product) and selective knockdown of basic helix-loop-helix factors [hairy enhancer of split (HES) gene and Hes-related transcription (Hrt) factors Hrt-1, Hrt-2, and Hrt-3] using targeted small interfering RNA. Cells cultured under conditions of defined equibiaxial cyclic strain (10% strain, 60 cycles/min, 24 h) exhibited a significant reduction in Notch 1 IC and Notch 3 IC expression concomitant with a significant increase in VSMC differentiation marker expression. Moreover, this cyclic strain-induced increase was further enhanced after inhibition of CBF-1/RBP-Jkappa-dependent signaling with RPMS-1. These findings suggest that Notch promotes changes in hVSMC phenotype via activation of CBF-1/RBP-Jkappa-dependent pathways in vitro and contributes to the phenotypic response of VSMCs to cyclic strain-induced changes in VSMC differentiation.


Assuntos
Diferenciação Celular/fisiologia , Proteínas de Ligação a DNA/metabolismo , Músculo Liso Vascular/fisiologia , Proteínas Nucleares/metabolismo , Proteínas Proto-Oncogênicas/metabolismo , Receptores de Superfície Celular/metabolismo , Fatores de Transcrição/metabolismo , Actinas/biossíntese , Regulação para Baixo , Humanos , Proteína de Ligação a Sequências Sinal de Recombinação J de Imunoglobina , Fenótipo , Receptor Notch1 , Receptor Notch4 , Receptores Notch , Transdução de Sinais
10.
Circ Res ; 96(5): 567-75, 2005 Mar 18.
Artigo em Inglês | MEDLINE | ID: mdl-15705961

RESUMO

Notch signaling has been shown recently to regulate vascular cell fate in adult cells. By applying a uniform equibiaxial cyclic strain to vascular smooth muscle cells (SMCs), we investigated the role of strain in modulating Notch-mediated growth of SMCs in vitro. Rat SMCs cultured under conditions of defined equibiaxial cyclic strain (0% to 15% stretch; 60 cycles/min; 0 to 24 hours) exhibited a significant temporal and force-dependent reduction in Notch 3 receptor expression, concomitant with a significant reduction in Epstein Barr virus latency C promoter-binding factor-1/recombination signal-binding protein of the Jkappa immunoglobulin gene-dependent Notch target gene promoter activity and mRNA levels when compared with unstrained controls. The decrease in Notch signaling was Gi-protein- and mitogen-activated protein kinase-dependent. In parallel cultures, cyclic strain inhibited SMC proliferation (cell number and proliferating cell nuclear antigen expression) while significantly promoting SMC apoptosis (annexin V binding, caspase-3 activity and bax/bcl-x(L) ratio). Notch 3 receptor overexpression significantly reversed the strain-induced changes in SMC proliferation and apoptosis to levels comparable to unstrained control cells, whereas Notch inhibition further potentiated the changes in SMC apoptosis and proliferation. These findings suggest that cyclic strain inhibits SMC growth while enhancing SMC apoptosis, in part, through regulation of Notch receptor and downstream target gene expression.


Assuntos
Músculo Liso Vascular/citologia , Miócitos de Músculo Liso/fisiologia , Proteínas Proto-Oncogênicas/fisiologia , Receptores de Superfície Celular/fisiologia , Transdução de Sinais/fisiologia , Fatores de Transcrição/fisiologia , Animais , Apoptose/fisiologia , Divisão Celular/fisiologia , Células Cultivadas/fisiologia , Proteínas de Ligação a DNA/fisiologia , Regulação da Expressão Gênica , Proteína de Ligação a Sequências Sinal de Recombinação J de Imunoglobina , Proteínas Nucleares/fisiologia , Proteínas Proto-Oncogênicas/antagonistas & inibidores , Proteínas Proto-Oncogênicas/biossíntese , Proteínas Proto-Oncogênicas/genética , Proteínas Proto-Oncogênicas c-bcl-2/biossíntese , Proteínas Proto-Oncogênicas c-bcl-2/genética , RNA Mensageiro/biossíntese , RNA Mensageiro/genética , RNA Interferente Pequeno/farmacologia , Ratos , Receptor Notch1 , Receptores de Superfície Celular/antagonistas & inibidores , Receptores de Superfície Celular/biossíntese , Receptores de Superfície Celular/genética , Proteínas Recombinantes de Fusão/antagonistas & inibidores , Proteínas Recombinantes de Fusão/biossíntese , Proteínas Recombinantes de Fusão/genética , Proteínas Recombinantes de Fusão/fisiologia , Estresse Mecânico , Fatores de Transcrição/genética , Transfecção , Proteína X Associada a bcl-2 , Proteína bcl-X
11.
Auton Neurosci ; 111(2): 110-5, 2004 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-15182740

RESUMO

The aim of this study was to examine the role of neuronal nitric oxide (NO) on vagal regulation of the rat heart in vitro using the neuronal nitric oxide synthase (nNOS) inhibitor 1-(2-trifluoromethylphenyl) imidazole (TRIM). All experiments were carried out in the presence of the beta-adrenoreceptor antagonist atenolol (4 microM). Right thoracic vagus, or its cardiac branch, was stimulated at frequencies of 2, 4, 8, 16 and 32 Hz (pulse duration 1 ms, 20 V, for 20 s) before and after addition of TRIM (0.14 mM) and cardiac interval (ms) assessed. There was a significant positive linear correlation between cardiac interval and vagal frequency giving a slope of 2.76+/-0.8 ms/Hz (slope+/-S.E. slope; data pooled from eight rats) which was significantly attenuated following TRIM to 0.4+/-0.6 ms/Hz (P<0.05 ANOVA; n=8 rats). Nicotine applied in cumulative concentrations (0.03, 0.1, 0.3, 0.5, 1 mM) caused a linear concentration-dependent increase in cardiac interval, with a slope of 403+/-72 ms/mM (n=10 rats) which was significantly attenuated after treatment with hexamethonium (28 microM), to 190+/-36 ms/mM (n=10 rats, P<0.05 ANOVA), and atropine (3 microM) 100+/-31 ms/mM (n=9 rats, P<0.05 ANOVA) but not following TRIM (0.14 mM) 262+/-48 ms/mM (n=9 rats, P<0.05 ANOVA). These results suggest that NO facilitates vagal effects on the rat heart in vitro by an action at the pre-ganglionic/post-ganglionic synapse.


Assuntos
Frequência Cardíaca/fisiologia , Óxido Nítrico/metabolismo , Nó Sinoatrial/inervação , Nervo Vago/enzimologia , Animais , Atenolol/farmacologia , Frequência Cardíaca/efeitos dos fármacos , Imidazóis/farmacologia , Técnicas In Vitro , Masculino , Nicotina/farmacologia , Agonistas Nicotínicos/farmacologia , Óxido Nítrico Sintase/antagonistas & inibidores , Óxido Nítrico Sintase/metabolismo , Óxido Nítrico Sintase Tipo I , Ratos , Ratos Wistar , Nó Sinoatrial/fisiologia , Simpatolíticos/farmacologia
12.
J Pain Symptom Manage ; 27(6): 481-91, 2004 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-15165646

RESUMO

To characterize a new, one-stop multidisciplinary palliative care (MD) clinic which offers standardized multidisciplinary assessment, specific care recommendations, patient and family education, and on-site counseling, we retrospectively compared the assessments of 138 consecutive patients with advanced cancer referred to the MD clinic and 77 patients referred to a traditional pain and symptom management (PSM) clinic. The two groups were similar in tumor type, demographics, and symptom distress. The MD clinic team (physicians; nurses; pharmacists; physical, speech, and occupational therapists; social workers; chaplains; nutritionists; psychiatric nurse practitioner) delivered 1,066 non-physician recommendations (median 4 per patient, range 0-37). The PSM clinic team made no non-physician recommendations, but referred 14 patients to other medical specialists. In 80 (58%) MD-clinic patients with follow-up 9 days (median) after assessment, significant improvement was observed in pain, nausea, depression, anxiety, sleep, dyspnea, and well-being, but not in fatigue, anorexia, or drowsiness. In 83 patients interviewed after the MD clinic, satisfaction was rated as excellent (5 out of 5) in 86-97% of seven areas. Assessment at an MD clinic results in a high number of patient care recommendations, improved symptoms, and high levels of patient satisfaction.


Assuntos
Neoplasias/epidemiologia , Neoplasias/terapia , Clínicas de Dor/estatística & dados numéricos , Manejo da Dor , Dor/epidemiologia , Cuidados Paliativos/métodos , Cuidados Paliativos/estatística & dados numéricos , Garantia da Qualidade dos Cuidados de Saúde/métodos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Japão/epidemiologia , Masculino , Pessoa de Meia-Idade , Neoplasias/psicologia , Ambulatório Hospitalar/estatística & dados numéricos , Dor/psicologia , Medição da Dor , Cuidados Paliativos/psicologia , Satisfação do Paciente/estatística & dados numéricos , Reprodutibilidade dos Testes , Estudos Retrospectivos , Sensibilidade e Especificidade , Resultado do Tratamento
13.
J Clin Oncol ; 22(1): 185-92, 2004 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-14701781

RESUMO

PURPOSE: To compare the effectiveness and side effects of methadone and morphine as first-line treatment with opioids for cancer pain. PATIENTS AND METHODS: Patients in international palliative care clinics with pain requiring initiation of strong opioids were randomly assigned to receive methadone (7.5 mg orally every 12 hours and 5 mg every 4 hours as needed) or morphine (15 mg sustained release every 12 hours and 5 mg every 4 hours as needed). The study duration was 4 weeks. RESULTS: A total of 103 patients were randomly assigned to treatment (49 in the methadone group and 54 in the morphine group). The groups had similar baseline scores for pain, sedation, nausea, confusion, and constipation. Patients receiving methadone had more opioid-related drop-outs (11 of 49; 22%) than those receiving morphine (three of 54; 6%; P =.019). The opioid escalation index at days 14 and 28 was similar between the two groups. More than three fourths of patients in each group reported a 20% or more reduction in pain intensity by day 8. The proportion of patients with a 20% or more improvement in pain at 4 weeks in the methadone group was 0.49 (95% CI, 0.34 to 0.64) and was similar in the morphine group (0.56; 95% CI, 0.41 to 0.70). The rates of patient-reported global benefit were nearly identical to the pain response rates and did not differ between the treatment groups. CONCLUSION: Methadone did not produce superior analgesic efficiency or overall tolerability at 4 weeks compared with morphine as a first-line strong opioid for the treatment of cancer pain.


Assuntos
Analgésicos Opioides/uso terapêutico , Metadona/uso terapêutico , Neoplasias/complicações , Dor/tratamento farmacológico , Dor/etiologia , Administração Oral , Adulto , Idoso , Idoso de 80 Anos ou mais , Analgésicos Opioides/efeitos adversos , Analgésicos Opioides/farmacologia , Preparações de Ação Retardada , Relação Dose-Resposta a Droga , Método Duplo-Cego , Feminino , Humanos , Masculino , Metadona/efeitos adversos , Metadona/farmacologia , Pessoa de Meia-Idade , Cuidados Paliativos , Pacientes Desistentes do Tratamento , Satisfação do Paciente
14.
Palliat Med ; 17(8): 659-63, 2003 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-14694916

RESUMO

CONTEXT: The symptomatic benefits of oxygen in patients with cancer who have nonhypoxic dyspnea are not well defined. OBJECTIVE: To determine whether or not oxygen is more effective than air in decreasing dyspnea and fatigue and increasing distance walked during a 6-minute walk test. PATIENTS AND METHODS: Patients with advanced cancer who had no severe hypoxemia (i.e., had an O2 saturation level of > or = 90%) at rest and had a dyspnea intensity of > or = 3 on a scale of 0-10 (0 = no shortness of breath, 10 = worst imaginable shortness of breath) were recruited from an outpatient thoracic clinic at a comprehensive cancer center. This was a double-blind, randomized crossover trial. Supplemental oxygen or air (5 L/min) was administered via nasal cannula during a 6-minute walk test. The outcome measures were dyspnea at 3 and 6 minutes, fatigue at 6 minutes, and distance walked. We also measured oxygen saturation levels at baseline, before second treatment phase, and at the end of study. RESULTS: In 33 evaluable patients (31 with lung cancer), no significant differences between treatment groups were observed in dyspnea, fatigue, or distance walked (dyspnea at 3 minutes: P = 0.61; dyspnea, fatigue, and distance walked at 6 minutes: P = 0.81, 0.37, and 0.23, respectively). CONCLUSIONS: Currently, the routine use of supplemental oxygen for dyspnea during exercise in this patient population cannot be recommended.


Assuntos
Ar , Dispneia/prevenção & controle , Neoplasias/complicações , Oxigenoterapia/métodos , Adulto , Idoso , Gasometria , Doença Crônica , Estudos Cross-Over , Método Duplo-Cego , Teste de Esforço , Fadiga/prevenção & controle , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
15.
J Pain Symptom Manage ; 26(3): 818-26, 2003 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-12967730

RESUMO

Perception of discomfort in dying patients is a risk factor for distress and bereavement among relatives. This study determined the perception of discomfort, the frequency of observed behaviors, and their association among relatives and among nurses who care for unresponsive dying patients. Sixty unresponsive dying patients' relatives and their nurses were asked to evaluate patient discomfort levels, the frequencies of six observed behaviors, and the suspected reasons for the patient discomfort. The mean levels of perceived discomfort were similar, but the association was poor between the relatives and the nurses. Relatives reported significantly more observed behaviors and associated more pain as a reason for patient discomfort than did nurses. The findings suggest that relatives are intensely attuned to their loved ones' conditions and reactions, and nurses' responses are fairly similar. Further research is warranted, however, to distinguish between the distress that the relatives perceive and the actual suffering of patients.


Assuntos
Estado Terminal , Família/psicologia , Neoplasias/fisiopatologia , Enfermeiras e Enfermeiros/psicologia , Dor/fisiopatologia , Percepção , Adulto , Comportamento , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Dor/psicologia , Estudos Prospectivos
16.
J Pain Symptom Manage ; 26(1): 637-43, 2003 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-12850646

RESUMO

The majority of cancer patients wish to die at home. Improved understanding of place of death and its relevant demographic predictors is important for the planning of palliative cancer care programs. The purpose of this study was to determine the place and predictors of site of death in cancer patients in a major U.S. metropolitan area. Death certificate data over two years were analyzed for Houston area residents with cancer who died in the Houston area. Information was obtained on factors that might be associated with the place where cancer patients die. For the purpose of this study, we looked at the following variables: primary site of cancer (hematological, breast, genitourinary, gastrointestinal, lung, and other); black, white, Hispanic, or Asian; age at death; marital status; sex; whether or not veteran of U.S. armed forces; levels of education; and area of residency within the Houston area. Univariate and multivariate analyses were performed. The majority of patients died in the hospital (51-52% both years), with the next most frequently occurring group dying at home (34-35% both years). Stepwise multivariate analysis resulted in a 6-variable logistic regression model. In this model, the odds of dying in hospital were increased by a factor of 2.7 if the patient had a hematological cancer (P<0.0001), a factor of 1.6 if the patient lived in Harris County (P<0.0001), and a factor of 1.5 if the patient was black (P<0.0001). Further characterization of factors associated with increased risk of hospital death rate is needed and systems should be developed to enable the majority of cancer patients to access palliative care services in the multiple settings in which they die.


Assuntos
Serviços de Assistência Domiciliar/estatística & dados numéricos , Hospitalização/estatística & dados numéricos , Neoplasias/mortalidade , Cuidados Paliativos/estatística & dados numéricos , Idoso , Atestado de Óbito , Feminino , Humanos , Modelos Logísticos , Masculino , Texas/epidemiologia , População Urbana/estatística & dados numéricos
17.
J Pain Symptom Manage ; 25(5): 412-9, 2003 May.
Artigo em Inglês | MEDLINE | ID: mdl-12727038

RESUMO

The purpose of this study was to determine the helpfulness of a prompt sheet versus a general information sheet for patient communication with physicians. Sixty women with breast cancer attending their first outpatient consultation with a breast medical oncologist were randomized to receive either a prompt sheet (PS) or a general information (GI) sheet regarding breast cancer. Analysis of the results found that helpfulness of the written material was rated higher in the PS group (8.5 +/- 2) than the GI group (6.2 +/- 3.6), P = 0.005. The mean score of helpfulness in communicating with physicians was 7.9 +/- 2.4 and 5.7 +/- 3.8, respectively, P = 0.01. There were no significant differences between the groups in the average total number of questions asked by the patients or average physician or patient speaking time. We conclude that a disease-specific prompt sheet provided before medical encounters may assist in communication between patients and physicians.


Assuntos
Assistência Ambulatorial , Neoplasias da Mama/terapia , Consultores , Disseminação de Informação , Educação de Pacientes como Assunto , Percepção , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Pessoa de Meia-Idade , Satisfação do Paciente
19.
J Palliat Med ; 5(2): 319-27, 2002 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-12006235

RESUMO

The delivery of palliative care can vary greatly between countries depending on socioeconomic conditions and cultural issues. The evolution and development of palliative care varies greatly and influences the development of palliative care models. Models of palliative care in three different countries are discussed and suggestions are made for the future development of palliative care in developing and developed countries.


Assuntos
Atenção à Saúde/organização & administração , Cuidados Paliativos , Argentina , Canadá , Atenção à Saúde/economia , Política de Saúde/tendências , Humanos , Espanha
20.
J Clin Oncol ; 20(8): 2127-33, 2002 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-11956274

RESUMO

PURPOSE: To help with planning of a palliative care program, we reviewed the place of death of patients who were registered at our comprehensive cancer center and explored factors that predicted death in the hospital versus death at home. PATIENTS AND METHODS: A retrospective study was undertaken of local patients who were registered at the University of Texas M.D. Anderson Cancer Center and died during the 1997/1998 fiscal year. Data from the institutional tumor registry and from the State of Texas Bureau of Vital Statistics file were collected and analyzed. The main outcome measures were place of death, patient characteristics associated with place of death, and time from registration at the institution to death. RESULTS: Of 1,793 local patients, 251 (14%) died at M.D. Anderson Cancer Center; the remaining 86% died elsewhere. A total of 617 (34%) died at home, and 929 (52%) died in an acute hospital setting (including M.D. Anderson). A total of 1,040 (58%) died within 2 years of registration. The risk of hospital death versus home death increased for patients with cancer at a hematologic site (odds ratio [OR], 4.4; 95% confidence interval [CI], 2.8 to 6.8) and black ethnicity (OR, 1.9; 95% CI, 1.4 to 2.6) and decreased for patients who paid with Medicare (OR, 0.71; 95% CI, 0.57 to 0.90). CONCLUSION: Most patients died in an acute care hospital setting and within 2 years of registration. Our data show some predictors of hospital death for cancer patients and suggest that better hospital palliative care services and integrated palliative care systems that bridge community and acute hospitals are needed.


Assuntos
Institutos de Câncer , Mortalidade Hospitalar , Neoplasias/mortalidade , Neoplasias/terapia , Cuidados Paliativos , Assistência Terminal , Institutos de Câncer/estatística & dados numéricos , Continuidade da Assistência ao Paciente , Humanos , Modelos Logísticos , Análise Multivariada , Estudos Retrospectivos , Texas
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