ABSTRACT
Over the last years EU have been working on the development of a common classification system for health indicators. In connection with prevention and health promotion, a classification system has now been developed: the European Health Promotion Indicator Development, EUHPID. The purpose has been to establish a system of indicators to advance the focus on health promotion. Furthermore, the EUHPID can be used as a planning tool to generate higher consistency between different health promotion initiatives and other policy initiatives. This article discusses the model and its relevance in a Danish context.
Subject(s)
Global Health , Health Promotion , Health Status Indicators , European Union , Health Policy , Health Promotion/classification , Health Promotion/methods , Humans , International Cooperation , Models, Theoretical , Socioeconomic FactorsABSTRACT
The article discusses and describes how healthcare reform from 2007 in Denmark has influenced the health sector. This reform has been labelled the most radical reform of the political administrative system since the first democratic constitution in 1849. Local government reform is the latest step in a process of reforming the welfare state and the health sector. In more concrete terms this article analyzes two key issues that have had top priority in the first period of reform implementation - the new planning of hospital structure and the first generation of health agreements.
Subject(s)
Health Care Reform , Health Planning , Health Policy , Denmark , Health Care Reform/history , Health Planning/history , Health Policy/history , History, 20th Century , History, 21st Century , HumansABSTRACT
PURPOSE: We did a phase I dose-escalation trial to evaluate the feasibility and safety of intratumoral injections of C Cure 709, an allogeneic, continuous CTL cell line that, restricted by HLA-A2, recognizes MART-1-positive tumor cells through transduction with a T-cell receptor encoding gene. EXPERIMENTAL DESIGN: Cells were administered intratumorally in four dose levels ranging from 10(8) to 10(9) cells/d on days 1, 4, 7, 10, 14, and 28 of each treatment cycle to patients with metastatic melanoma. Main inclusion criteria were HLA-A2 tissue type, MART-1-positive tumor cells, and metastases suitable for ultrasound-guided injections. Patients were assessed for toxicity and response. Three to six patients were treated per dose level. Patients without progressive disease were offered up to three treatment cycles. RESULTS: Fifteen patients received a total of 24 treatment cycles with a total of 266 injections of C Cure 709. Toxicity was minor to moderate and most common injection site reactions were fever, fatigue, nausea/vomiting, and arthralgia/myalgia. Side effects disappeared in general within 24 hours. Toxicity was not dose dependent. One patient obtained a partial response, encompassing both metastases used and not used for intratumoral injections. Remaining patients did not achieve an overall response. In addition, we observed local regression of metastases used for injection in two patients and of metastases not used for injection in one patient. CONCLUSION: Intratumoral injections of C Cure 709 are feasible, safe, and capable of inducing tumor regression. Further investigation in a phase II setting is warranted.
Subject(s)
Immunotherapy, Adoptive/methods , Melanoma/therapy , Receptors, Antigen, T-Cell/immunology , T-Lymphocytes, Cytotoxic/immunology , Adult , Antigens, Neoplasm , Cell Line , Fatigue/etiology , Feasibility Studies , Female , Fever/etiology , HLA-A2 Antigen/immunology , Humans , Immunotherapy, Adoptive/adverse effects , MART-1 Antigen , Male , Melanoma/secondary , Middle Aged , Nausea/etiology , Neoplasm Proteins/immunology , T-Lymphocytes, Cytotoxic/metabolism , T-Lymphocytes, Cytotoxic/transplantation , Transplantation, Homologous , Treatment OutcomeABSTRACT
PURPOSE: It has been hypothesized that tumor cells expressing Fas ligand (FasL) might be able to counterattack and neutralize tumor-infiltrating lymphocytes. We assessed the effect of FasL tumor counterattack on the clinical outcome of interleukin-2 (IL-2)-based immunotherapy in metastatic renal cell carcinoma. EXPERIMENTAL DESIGN: Tumor core needle biopsies were obtained before IL-2-based immunotherapy in 86 patients and repeated within the first cycle in 57 patients. Tumor cells expressing FasL and intratumoral lymphocyte subsets expressing CD4, CD8, CD56, and CD57 were analyzed by immunohistochemistry. RESULTS: At baseline, negative FasL staining in tumor cells was seen in 10 of 86 (12%) biopsies, whereas intense FasL staining was seen (a) in fewer than 10% of tumor cells in 26 (30%) biopsies; (b) in 11 to 50% of tumor cells in 25 (29%) biopsies; (c) in 51 to 90% of tumor cells in 18 (21%) biopsies; and (d) in >90% of tumor cells in 7 (8%) biopsies. On treatment, tumor FasL expression did not change from baseline levels. Moreover, tumor FasL expression was not correlated with objective response or survival whereas the absolute number of CD4(+), CD8(+), CD56(+), and CD57(+) cells per mm(2) tumor tissue at baseline was significantly higher in responding patients compared with nonresponding patients (P = 0.01, P = 0.008, P = 0.015, and P < 0.001, respectively). During the first course of immunotherapy, the absolute number of CD4(+), CD8(+), and CD57(+) cells per mm(2) tumor tissue was significantly higher in responding patients compared with nonresponding patients (P = 0.034, P < 0.001, and P < 0.001, respectively). However, no correlation was observed between the number of intratumoral lymphocytes and tumor FasL expression level. CONCLUSION: These observations do not support the hypothesis that FasL tumor "counterattack" has an effect on the clinical outcome in metastatic renal cell carcinoma during IL-2-based immunotherapy.
