Comparative toxicities of 3 platinum-containing chemotherapy regimens in relapsed/refractory lymphoma patients.

Optimal salvage chemotherapy regimen for patients with relapsed or refractory Hodgkin and non-Hodgkin lymphoma remains unclear but often based on platinum regimens. This retrospective study assesses in real life the toxicities profiles of patients with relapsed or refractory lymphoma treated with DHA (dexamethasone, high dose aracytine cytarabine) plus platinum salt (dexamethasone-High dose aracytine (cis)platin (DHAP), dexamethasone-High dose aracytine carboplatin (DHAC), or dexamethasone-High dose aracytine Oxaliplatin (DHAOX)), from February 2007 to May 2013 in 2 French hospitals. Toxicities were recorded from medical files and assessed according to the National Cancer Institute Common Toxicity Criteria version 3.0. Potential risk factors of renal insufficiency were tested by univariate analyses. A total of 276 patients were treated: 168 with DHAP (60.9%), 79 with DHAOX (28.6%), and 29 with DHAC (10.5%). Rituximab was associated in 80.1% of patients (n = 221). Renal failure was reported in 97 patients, mainly with cisplatin regimen (86.6%) leading to 8.9% grade III to IV renal failure (P = .001). Renal insufficiency was reversible in most patients but remained persistent in 24, with all of them being treated with DHAP except 1. Cisplatin-based regimen (50.0% versus 12.0%, P < .05) and female (44.6% versus 29.7%, P < .05) appeared to be at higher risks of renal failure. Platinum cumulative dose is a significant risk factor of nephrotoxicity. Hematologic toxicity was more frequent with carboplatin and cisplatin with at least 1 event (all toxicity grade) respectively in 79.3% and 71.4% of patients treated (P < .005). Auditory toxicity was mainly reported with cisplatin (n = 19; 4 grade I-II and 15 grade III-IV). Oxaliplatin was implicated in 77.6% of neurotoxicity (n = 59), mainly moderate (grade I-II). In conclusion, DHAOX and DHAC regimens have more favorable toxicity profile than DHAP regimen. Their lack of renal toxicity makes them attractive regimens, which may be interesting for patients eligible for autologous stem cell transplantation. Nevertheless, these results have to be confirmed by the therapeutic efficacy of these 3 regimens.

Is rapid organ recovery a good idea? An exploratory study of the public's knowledge and attitudes.

In 2006, the Institute of Medicine (IOM) recommended demonstration projects on uncontrolled donation after cardiac death or rapid organ recovery (ROR). To investigate what the public thinks about key ethical and policy questions associated with ROR, 70 African-American, Caucasian and Latino community members in St. Louis, MO, participated in focus groups and completed surveys, before and after being educated about ROR. Before the focus group, most participants believed mistakenly that they could donate organs following an unexpected cardiac arrest (76%). After the focus group, 84% would want to donate organs after unexpected cardiac arrest; 81% would support organ cooling to enable this. The public generally supported organ cooling without family consent if the individual had joined the donor registry, but were mixed in their opinions about what should be done if they were not on the registry. African-American and Latino participants expressed greater fears than Caucasians that if they consented to organ donation, physicians might do less to save their life; however, support for ROR was not significantly lower in these subgroups. Although this study is exploratory, public support for ROR was present. We recommend that adequate consent processes and safeguards be established to foster trust and support for ROR.

Stopping trials early for commercial reasons: the risk-benefit relationship as a moral compass.

Decisions by industry sponsors to end clinical trials early for commercial reasons have been the subject of controversy. I argue that the principal consideration in assessing these decisions ought to be the way in which the termination would affect the trial's risk-benefit relationship. If there is not yet sufficient benefit to be gained from the study to offset the risks to which participants were exposed and it is expected that important scientific information would be obtained if the trial were continued, early termination constitutes an unethical alteration of the risk-benefit relationship. This violates the grounds on which permission is given to conduct human research, patients consent to participate, and investigators agree to conduct studies. These knowable and avoidable changes in risk-benefit relationship should generally be seen as impermissible.

Institutional integrity in Roman Catholic health care institutions.

Issues of institutional identity and integrity in Roman Catholic health care institutions have been addressed at the level of individual institutions as well as by organizations of Catholic health care providers and at various levels in the Church hierarchy. The papers by Carol Taylor, C.S.F.N., Thomas Shannon, Kevin O'Rourke, O.P., Gerard Magill in this volume provide a significant contribution to concerns of Roman Catholic health care institutions as they face the challenges of providing health care in a secular, pluralistic, market-driven economy. One way to understand institutional integrity is as a measure of the coherence between what an institution identifies as its commitments (its stated moral character), what an institution does (its manifest moral character) and an institution's fundamental moral commitments (its deep moral character). The essays in this volume support this model of integrity. Although it is not their explicit focus, the four essays together provide a vision of institutional integrity for Catholic health care institutions. Each author focuses on one of the three central aspects of integrity: what one identifies as one's commitments (Taylor), how one's actions reflect one's values (Shannon and Magill), and what one is or what one values at a deep level (O'Rourke). I will offer a brief overview of the ways in which the integrity of Catholic health care institutions has been addressed. Then I will consider the four essays and show how each offers an analysis of one of the three critical elements of integrity.

Improved antibacterial activities of coumarin antibiotics bearing 5',5'-dialkylnoviose: biological activity of RU79115.

A new series of coumarin inhibitors of DNA gyrase B bearing a N-propargyloxycarbamate at C-3' of various 5',5'-dialkylnoviose, including RU79115, were synthesised and their antibacterial activities have been delineated. Introduction of dialkyl substituents at 5'5'-position of noviose leads to coumarin analogues with improved in vitro and in vivo antibacterial activity.

1,3-Disubstituted-2-carboxy quinolones: highly potent and selective endothelin A receptor antagonists.

The design, synthesis, and in vitro biological activity of a series of 2-carboxy quinolone antagonists selective for the endothelin A receptor are presented. Introduction of a second acid group in position 3 of the quinolone ring increases dramatically the selectivity for ET(A).

Bioethics as methodological case resolution: specification, specified principlism and casuistry.

Bioethical decision-making depends on presuppositions about the function and goal of bioethics. The authors in this issue of The Journal of Medicine and Philosophy share the assumption that bioethics is about resolving cases, not about moral theory, and that the best method of bioethical decision-making is that which produces useful answers. Because we have no universally agreed upon background moral theory which can serve as the basis for bioethical decision-making, they try to move bioethics away from theory. For them, a good method of bioethical decision-making is one which resolves cases in ways that are justifiable to the parties involved, not necessarily in ways that bring us "close" to the right and the true. The authors consider how the move away from theory and toward actual cases is best accomplished. In particular, the debate in this issue is about specification, specified principlism, and casuistry.