Variation in medication use in cancer patients at the end of life: a cross-sectional analysis.

PURPOSE: Despite advances in cancer treatment, patients still die with unnecessary suffering. Therefore, high-quality end-of-life care is needed. Variations in medication use at the end of life may suggest areas for improvement. This study aims to describe the use of medications during the last days of life of cancer patients and to explore the possibility of using it as a quality measure. METHODS: We conducted an international survey on experts' opinions regarding potentially inappropriate medications for dying patients. Subsequently, a chart review of deceased cancer patients was conducted, which assessed the current medication use in different settings. RESULTS: The mean number of medications used in the last 3 days of life was 4.8 (SD 2.1). Hospital patients were less likely than hospice patients to receive opioids, midazolam, haloperidol, and drugs for pulmonary secretions or nausea/vomiting. Over 90 % of experts rated 12 medications as unlikely to be appropriate. Hospital patients were more likely than hospice patients to receive these potentially inappropriate medications. Before the implementation of an end-of-life care pathway, hospital patients had a higher probability, than after, to receive potentially inappropriate medication. Moreover, after implementation of such pathway, patients for whom a pathway was not used were more likely to receive potentially inappropriate medications than patients for whom it was used. CONCLUSION: Medication use at the end of life varies widely by setting, both for potentially appropriate and inappropriate medications. Combining experts' opinion and current medication use resulted in the identification of 16 medications that might be used to assess the quality of cancer care at the end of life.

Molecular epidemiology of an outbreak of Legionnaires' disease associated with a cooling tower in Genova-Sestri Ponente, Italy.

Fatty acid profile analysis, monoclonal antibody (MAb) subtyping, pulsed-field gel electrophoresis (PFGE), arbitrarily primed polymerase chain reaction (AP-PCR), and ribotyping were used to compare clinical and environmental Legionella pneumophila serogroup 1 isolates from an outbreak of Legionnaires' disease presumptively associated with cooling towers. According to the Oxford subtyping scheme, the MAb subtype of patients' isolates and of two strains originating from a cooling tower was Pontiac, whereas the other isolates were subtype Olda. The strains showed no intrinsic strain-to-strain difference in fatty acid profiles, and ribotyping and length polymorphism of the 16S-23S rDNA intervening regions failed to reveal any differences between the isolates. Conversely, PFGE and AP-PCR appeared to be more discriminatory, as the same genomic profile was found for the clinical and some environmental strains. Meteorologic and epidemiological data and the results of molecular analysis of the Legionella pneumophila serogroup 1 isolates support the hypothesis that the infection was transmitted from one of the cooling towers to the indoor environment of the same building, to homes in proximity that had open windows, and to the streets. In fact, the outbreak diminished and later ended after a part in the tower was replaced. This investigation demonstrates the utility of combined molecular methods (i.e., phenotypic and genomic typing) in comparing epidemiologically linked clinical and environmental isolates. Finally, the outbreak confirms the risk of Legionnaires' disease posed by cooling towers, mainly when atmospheric thermal and humidity inversions occur. This finding emphasizes the need to determine whether the source of infection is in the living or working environment or somewhere else.

Cisplatin, 5-fluorouracil and alpha interferon in non small cell lung carcinoma: a toxicity study.

Data are presented on the general and hematological toxicity of a cisplatin (DDP), 5-fluorouracil (5-FU) and alpha interferon (IFN-alpha) association in patients with stage III B or IV non small cell lung cancer (NSCLC). Twenty patients received DDP (100 mg/mq i.v., day 1) and 5-FU (750 mg/mq/day i.v. continuous infusion, days 1 to 4). In ten of these patients IFN-alpha (3 MU s.c., three times weekly, days 1 to 21) was added. General and hematological toxicity was of a similar degree in both groups. Recombinant granulocyte colony stimulating factor (G-CSF; 5 micrograms/kg b.w. s.c. days 7 to 18) induced a sharp increase in peripheral blood GM-CFU level in patients receiving DDP and 5-FU but not in DDP, 5-FU, IFN-alpha treated patients. The results appear to indicate that IFN-alpha modulation of a DDP, 5-FU combination induces an acceptable degree of toxicity.

Protective effect on cisplatin hematotoxicity by procaine hydrochloride.

The ability of procaine hydrochloride (P.HCl) to modulate the effects of cisplatin (DDP) on pluripotent (CFU-S) and committed (CFU-GM) murine hemopoietic stem cells was investigated. DBA/2NCrlBRF1 mice received DDP alone (10 and 16 mg/kg body wt. single i.p. injection) or in combination with P.HCl (40 mg/kg body wt. single i.p. injection). Hemopoietic progenitor cell (HPC) time survival curves were determined up to 14 days following treatment. The simultaneous administration of the lower DDP dose together with P.HCl greatly reduced the hemotoxicity of the antitumoral drug, while this protection was not significant with the higher DDP dose. These results support a role for P.HCl in protecting against DDP hematological toxicity.

Effect of atrazine on hemopoietic system.

For a long time some pesticides (chlordane, lindane, DDT) have been associated with bone marrow aplasia. Little is known on the toxic activity of the herbicides s-triazines on hemopoiesis. We studied the effect of one of these compounds (atrazine) on mouse hemopoietic progenitors (CFU-S and GM-CFC) and on peripheral blood (leukocytes and reticulocytes) after a single i.p. injection of 58.65 mg/kg. The peripheral blood leukocyte level was not modified; on the contrary, reticulocytes dropped severely but recovered promptly. Hemopoietic progenitors were severely hit but they recovered and reached normal levels in a few days. Our results demonstrate a hemotoxic effect of atrazine. However, more data are needed, especially in experiments with chronic exposure.

Hemotoxic effects on mice of combined administration of azidothymidine and acyclovir.

This study reports the effects of a combination of azidothymidine (AZT) plus acyclovir (ACV) on both pluripotent (spleen colony-forming units, CFU-S) and committed (granulocyte-macrophage colony-forming units, CFU-GM; erythroid burst-forming units, BFU-E) murine hemopoietic progenitors. Administration of AZT alone was associated with severe hemotoxicity, as shown by the marked decrease of all the hemopoietic progenitor populations tested, that is, CFU-S, CFU-GM, and BFU-E. This, however, was followed by a prompt recovery of hemopoiesis. Administration of ACV alone did not modify the hematological parameters studied, whereas the combined administration of AZT and ACV led to changes in peripheral blood cells and bone marrow hemopoietic progenitors that were, on the whole, not significantly different from those observed with AZT alone. Only the decrease in CFU-S was significantly more severe, but their recovery was as rapid as that of the committed progenitors. Thus, in this experimental setting, the addition of ACV to AZT does not appear to increase the hemotoxicity of the latter.

Leucovorin antagonizes the effects of trimetrexate on mouse hemopoietic progenitors.

Trimetrexate (2, 4, diamino -5- methyl - 6 [3, 4, 5, trimethoxyanilino) methyl] quinazoline) (TMQ) is a non-classic folate antagonist that is used as an antineoplastic and antipneumocystis agent with promising results. TMQ and methotrexate (MTX) toxicities are comparable. Leucovorin (N-5-formyltetrahydrofolate) (LV) is used to prevent the toxic effects of MTX. In this study the effects of LV on TMQ induced hemopoietic progenitor damage are studied in a murine model. Changes of pluripotent stem cells (colony forming units spleen, CFU-S), granulocyte-macrophage committed progenitors (GM-CFC), erythroid committed progenitor (BFU-E) levels in the bone marrow were followed after administration to mice of a single dose of TMQ or of simultaneous injection of TMQ and LV. Results show that the latter significantly reduces the effects of the former on peripheral blood cells and on hemopoietic progenitors.

Dideoxycytidine toxicity on mouse hemopoietic progenitors.

Several antiviral compounds showed a toxicity or hemopoietic progenitor cells, 2', 3' Dideoxycytidine (ddc) is the most potent drug in vitro against human T cell lymphotropic viruses and is now being tested on patients with AIDS and AIDS-related complex. We studied its toxicity on mouse hemopoietic progenitors. Results reported here show a toxic activity of ddc but further studies are required to ascertain whether this toxicity is of significance during clinical application.

Toxicity of vidarabine on hemopoietic progenitor cells in mice.

9 beta-D-Arabinofuranosyladenine (adenine arabinoside, vidarabine, ara-A), is employed as an antiviral compound mainly against herpes virus infections. Toxicity of ara-A is of concern in clinical applications. This work reports quantitative changes of bone marrow hemopoietic progenitors in mice treated with ara-A. The experimental model is based on time survival curves following repeated intraperitoneal injections (200, 400 or 800 mg/kg twice a day for 4 days) of different doses of the drug. Our results show that ara-A causes damage to the hemopoietic progenitors. The induced damage is roughly proportional to the injected amount of the drug. Following termination of ara-A administration all tested populations rapidly recovered.