RESUMO
BACKGROUND: Patients with heart failure have palliative care needs that can be effectively addressed by specialist palliative care (SPC). Despite this, SPC utilization by this patient population is low, suggesting barriers to SPC referral. We sought to determine the referral practices of cardiologists to SPC. METHODS: Cardiologists across Canada were invited to participate in a survey about their referral practices to SPC. Associations between referral practices and demographic, professional, and attitudinal factors were analyzed using multiple and logistic regression. RESULTS: The response rate was 51% (551 of 1082). Between 35.1% and 64.2% of respondents were unaware of referral criteria to local SPC services. Of the respondents, 29% delayed SPC referral because of prognostic uncertainty, and 46.8% believed that SPC prioritizes patients with cancer. In actual practice, nearly three-fourths of cardiologists referred late. Referral frequency was associated with greater availability of SPC services for patients with nonmalignant diseases (P = 0.008), a higher number of palliative care settings accepting patients receiving continuous infusions or pursuing acute care management (P < 0.001), satisfaction with services (P < 0.001), and less equation of palliative care with end-of-life care (P < 0.001). Early timing of referral was associated with greater availability of SPC services for patients with nonmalignant diseases and less equation of palliative care with end-of-life care. CONCLUSIONS: The findings suggest that barriers to timely SPC referral include an insufficiency of services for patients with nonmalignant diseases especially in the outpatient setting, the perception that SPC services do not accept patients receiving cardiology-specific treatments, and a misperception about the identity of palliative care.
CONTEXTE: Les services de soins palliatifs spécialisés (SPS) peuvent répondre efficacement aux besoins des patients présentant une insuffisance cardiaque. Malgré tout, les patients de cette population n'ont pas beaucoup recours aux SPS, ce qui semble indiquer la présence d'obstacles à l'orientation vers les SPS. Nous avons entrepris de déterminer les pratiques des cardiologues en matière d'orientation des patients vers les SPS. MÉTHODOLOGIE: Les cardiologues de partout au Canada ont été invités à participer à un sondage sur leurs pratiques en matière d'orientation des patients vers les SPS. Les associations entre ces pratiques et certaines caractéristiques démographiques, professionnelles et comportementales ont été analysées au moyen d'une régression multiple et logistique. RÉSULTATS: Le taux de participation au sondage a été de 51 % (551 réponses sur 1 082 invitations). Entre 35,1 et 64,2 % des répondants ne connaissaient pas les critères pour l'orientation des patients vers les services locaux de SPS. Parmi les répondants, 29 % ont dit reporter l'orientation vers les SPS en raison du caractère incertain du pronostic, et 46,8 % croyaient que les SPS s'adressaient en priorité aux patients atteints d'un cancer. Dans la pratique, près des trois quarts des cardiologues ont orienté tardivement les patients. La fréquence des orientations a été associée à une disponibilité plus grande de services de SPS pour les patients atteints de maladies non cancéreuses (p = 0,008), à un nombre plus élevé de milieux de soins palliatifs admettant les patients nécessitant des perfusions continues ou prenant en charge les soins actifs (p < 0,001), à la satisfaction à l'égard des services (p < 0,001) et à une assimilation moins importante des soins palliatifs avec les soins de fin de vie (p < 0,001). L'orientation rapide des patients était associée à une disponibilité plus grande de services de SPS pour les patients atteints de maladies non cancéreuses et à une assimilation moins importante des soins palliatifs avec les soins de fin de vie. CONCLUSIONS: Nos observations semblent indiquer que l'insuffisance des services destinés aux patients atteints de maladies non cancéreuses (en particulier dans le contexte des soins ambulatoires), la perception que les services de SPS n'admettent pas les patients nécessitant des traitements en cardiologie et la perception erronée de la finalité des soins palliatifs constituent des obstacles à l'orientation des patients vers les SPS en temps opportun.
RESUMO
Defects in apoptosis mechanisms contribute to chemoresistance in malignancy. However, correlations of apoptosis-regulating proteins with clinical outcome in cancer patients are variable, presumably reflecting the difficulty of using static tests of gene expression in a scenario influenced by a dynamic interplay of multiple pro- and antiapoptotic molecules. Therefore, we assessed the functional integrity of apoptosis pathways in intact primary leukemia cells and correlated the functional status of these pathways with clinical outcome. Active apoptogenic proteins were introduced into primary leukemia cells by electroporation followed by measurement of active caspases by flow cytometric techniques. Cytochrome c was introduced to activate the intrinsic (mitochondrial) pathway, whereas caspase-8 was introduced to activate the extrinsic (death receptor) pathway. In a series of 24 patients with acute myeloid leukemia, 79% had a block in at least one pathway, indicating that defects in caspase activation mechanisms are common in patients with leukemia. Simultaneous blocks in both pathways correlated with chemoresistant disease (92% of patients with chemoresistant disease versus 33% of patients with chemosensitive disease; P = 0.005) and decreased overall patient survival (35% versus 89% 1-year survival; P = 0.02). Simultaneous blockage of the intrinsic and extrinsic pathways could be explained by a defect located at a point of convergence of the two pathways, probably related to overexpression of endogenous inhibitors of the effector-caspases, rather than decreased levels of these proteases. This study supports the importance of apoptosis pathways in determining response to chemotherapy and suggests that functional defects in caspase activation are prognostic in patients with leukemia.