A closer look at lay sponsorship. A CHA survey reveals some problems with two established models

The private association of the Christian faithful (PACF) and private juridic person (PJP) are two lay sponsorship options for healthcare organizations that find traditional sponsorship unavailable. Today two questions relate to these models: Are the PACF and the PJP still realistic and attractive models of sponsorship? Can Catholic identity be maintained in them? Last summer CHA surveyed the seven member organizations that use either the PACF or the PJP as sponsorship models. In addition, CHA conducted four site visits, which corroborated the survey findings. Most respondents said their organizations had adopted the lay model as a means of remaining Catholic after their original sponsors withdrew. Most said they had a good relationship with the local diocese, although formal meetings with the diocesan leaders were infrequent. Each organization had a clearly articulated mission and reinforced their mission and values in various ways. Leadership development appeared somewhat weak. Some respondents spoke favorably of the PACF and PJP models of sponsorship, but others saw limitations, including isolation, lack of clarity in reporting mechanisms between the organization and the diocese, and lack of board education about the models. Even those who saw a future for lay sponsorship on the PACF and PJP models said that, although it is important for Catholic healthcare to develop lay leadership, these models are not promising steps in that direction.     

A phase I trial of the dual farnesyltransferase and geranylgeranyltransferase inhibitor L-778,123 and radiotherapy for locally advanced pancreatic cancer.

PURPOSE: Preclinical and clinical studies have demonstrated that inhibition of prenylation can radiosensitize cell lines with activation of Ras and produce clinical response in patients with cancer. The aim of this study was to determine the maximally tolerated dose of the dual farnesyltransferase and geranylgeranyltransferase I inhibitor L-778,123 in combination with radiotherapy for patients with locally advanced pancreatic cancer. EXPERIMENTAL DESIGN: L-778,123 was given by continuous intravenous infusion with concomitant radiotherapy to 59.4 Gy in standard fractions. Two L-778,123 dose levels were tested: 280 mg/m2/day over weeks 1, 2, 4, and 5 for dose level 1; and 560 mg/m2/day over weeks 1, 2, 4, 5, and 7 for dose level 2. RESULTS: There were no dose-limiting toxicities observed in the eight patients treated on dose level 1. Two of the four patients on dose level 2 experienced dose-limiting toxicities consisting of grade 3 diarrhea in one case and grade 3 gastrointestinal hemorrhage associated with grade 3 thrombocytopenia and neutropenia in the other case. Other common toxicities were mild neutropenia, dehydration, hyperglycemia, and nausea/vomiting. One patient on dose level 1 showed a partial response of 6 months in duration. Both reversible inhibition of HDJ2 farnesylation and radiosensitization of a study patient-derived cell line were demonstrated in the presence of L-778,123. K-RAS mutations were found in three of the four patients evaluated. CONCLUSIONS: The combination of L-778,123 and radiotherapy at dose level 1 showed acceptable toxicity in patients with locally advanced pancreatic cancer. Radiosensitization of a patient-derived pancreatic cancer cell line was observed.     

Taurine inhibition of metal-stimulated catecholamine oxidation

Taurine is an abundant amino acid found in mammalian tissues and it has been suggested to have cyto-protective functions. The aim of the present study was to determine if taurine had the potential to reduce oxidative stress associated with metal-stimulated catecholamine oxidation. Taurine and structural analogs of taurine were tested for their ability to inhibit metal-stimulated quinone formation from dopamine or L-dopa. Oxidative damage to proteins and lipids were also assessedin vitro and the effects of taurine were determined. Taurine (20 mM) was found to decrease significantly ferric iron (50–500 μM)- and manganese (10 μM)-stimulated L-dopa or dopamine oxidation. Taurine had no effect on zinc-induced dopamine oxidation and slightly potentiated copper- and NaIO₄-stimulated quinone formation. Ferric iron-stimulated lipid peroxidation was not affected by taurine (1–20 mM). Protein carbonyl formation induced by ferric iron (500 μM) and L-dopa (500 μM) was significantly reduced by 10 mM taurine. The cytotoxicity of L-dopa (250 μM) and ferric chloride (75 μM) to LLC-PK₁ cells was attenuated by 10 mM taurine or hypotaurine. Homotaurine alone stimulated L-dopa oxidation and potentiated the cytotoxic effects of ferric iron. Homotaurine was found to be cytotoxic when combined with L-dopa or L-dopa/iron. In contrast, hypotaurine inhibited quinone formation and protected LLC-PK₁ cells. These studies suggest that taurine may exhibit cytoprotective effects against the oxidation products of catecholamines by acting as a scavenger for free radicals and cytotoxic quinones.     

Cancer screening in the United States, 2013

Answer questions and earn CME/CNE Each year the American Cancer Society (ACS) publishes a summary of its recommendations for early cancer detection, a report on data and trends in cancer screening rates, and select issues related to cancer screening. In this issue of the journal, current ACS cancer screening guidelines are summarized, as are updated guidelines on cervical cancer screening and lung cancer screening with low‐dose helical computed tomography. The latest data on the use of cancer screening from the National Health Interview Survey also are described, as are several issues related to screening coverage under the Patient Protection and Affordable Care Act of 2010. CA Cancer J Clin 2013;. © 2013 American Cancer Society.     

Lack of effect of aprepitant on the pharmacokinetics of docetaxel in cancer patients

Background Aprepitant is a selective neurokinin-1 receptor antagonist that is effective for the prevention of nausea and vomiting caused by highly emetogenic chemotherapy. In vitro, aprepitant is a moderate inhibitor of the CYP3A4 enzyme, which is involved in the clearance of several chemotherapeutic agents. In this study we examined the potential for aprepitant to affect the pharmacokinetics and toxicity of intravenously administered docetaxel, a chemotherapeutic agent that is primarily metabolized by CYP3A4.Methods A total of 11 cancer patients (4 male, 7 female, aged 50–68 years) were enrolled in this multicenter, randomized, open-label, two-period, crossover study. Patients received a single infusion of docetaxel monotherapy, 60–100 mg/m², on two occasions at least 3 weeks apart. During one of the cycles (treatment A), patients received docetaxel alone. During the alternate cycle (treatment B), they also received aprepitant 125 mg orally 1 h prior to docetaxel infusion (day 1), and a single oral dose of aprepitant 80 mg on days 2 and 3. The pharmacokinetic profile of docetaxel was assessed over 30 h following docetaxel infusion. Blood counts were monitored on days 1, 4, 7, and 14.Results Ten patients completed the study. Concomitant administration of aprepitant did not cause any statistically or clinically significant changes in docetaxel pharmacokinetics. Values for docetaxel alone (treatment A) versus docetaxel with aprepitant (treatment B) were as follows: geometric mean AUC_0–last was 3.26 vs 3.17 g h/ml (P>0.25; ratio B/A 0.97); geometric mean AUC_0– 3.51 vs 3.39 g h/ml (P>0.25; ratio B/A 0.96); geometric mean C_max was 3.53 vs 3.37 g/ml (P>0.25; ratio B/A 0.95); and geometric mean plasma clearance was 23.3 vs 24.2 l/h/m² (P>0.25; ratio B/A 1.04). The corresponding harmonic mean half-life values were 10.1 and 8.5 h. The two treatment regimens had similar tolerability profiles; the median absolute neutrophil count nadirs were 681/mm³ during treatment with docetaxel alone and 975/mm³ during aprepitant coadministration.Conclusions Aprepitant had no clinically significant effect on either the pharmacokinetics or toxicity of standard doses of docetaxel in cancer patients. Aprepitant at clinically recommended doses may have a low potential to affect the pharmacokinetics of intravenous chemotherapeutic agents metabolized by CYP3A4.     

Cancer screening in the United States, 2011: A review of current American Cancer Society guidelines and issues in cancer screening

Each year the American Cancer Society (ACS) publishes a summary of its recommendations for early cancer detection, a report on data and trends in cancer screening rates, and select issues related to cancer screening. This article summarizes the current ACS guidelines, describes the anticipated impact of new health care reform legislation on cancer screening, and discusses recent public debates over the comparative effectiveness of different colorectal cancer screening tests. The latest data on the utilization of cancer screening from the National Health Interview Survey is described, as well as several recent reports on the role of health care professionals in adult utilization of cancer screening.