Phase I study of high-dose cytosine arabinoside and etoposide in patients with advanced malignancies

Summary Cytosine arabinsodie (ara-C) and etoposide (VP-16) display synergy in the laboratory. Twenty-six patients participated in a phase I study of high-dose ara-C in combination with VP-16. The dose of VP-16 was held constant at 50 mg/m² as an intermittent infusion over 33 h; escalating doses of ara-C were given as infusions during hours 9–12 and 21–24. Myelosuppression was the dose-limiting toxicity and occurred with doses considerably less than those expected from studies of the two drugs as single agents. The suggested initial doses for phase II trials with this schedule are 750 mg/m²×2 doses of ara-C and 50 mg/m² of VP-16. Nonhematologic toxicity was minimal; therefore, further dose escalation is feasible in patients in whom myelosuppression is acceptable.Supported in part by grants from the National Cancer Institute (CA-12197 and CA-09422) and the American Cancer Society CF-85-182     

Clerkship directors' perceptions of the impact of HCFA documentation guidelines.

PURPOSE: Chart notes are used to support billing codes under the evaluation and management guidelines of the Health Care Financing Administration (HCFA), in addition to serving as a record of the visit. To better understand the effect of the HCFA documentation guidelines, the authors collected data on how the guidelines affect participation by university- and community-based faculty in clinical education programs. METHOD: In 2000, the authors sent six copies of their questionnaire to the associate deans of the 125 U.S. medical schools and requested they distribute them to all core clerkship directors. The questionnaire consisted of multiple-choice and short-answer questions regarding documentation of medical visits, participation of community-based faculty, understanding of HCFA documentation guidelines, and effects on education programs. RESULTS: The response rate was about 50%. Most of the 379 clerkship directors who responded (77%) stated they were aware the HCFA documentation guidelines include specifications regarding the role medical students can play and documentation of medical visits, and 64% indicated they were concerned the guidelines would affect their educational programs. Concerns included the loss of student independence and active participation in the patient care environment (37), time constraints and the changing balance between education and service (16), loss of faculty and decreased morale (11), and decreased quality of care for patients (7). CONCLUSION: Leaders of medical education must work to modify these guidelines to protect the quality of patients' care, while maximizing students' educational opportunity and participation.     

Altered regulation of in-vivo coagulation in orthopedic patients prior to knee or hip replacement surgery.

Up to 20% of patients develop venographically proven deep-vein thrombosis after elective orthopedic surgery even under the cover of heparin or low molecular weight heparin. The extent to which the chronic inflammation of osteoarthritis requiring elective orthopedic surgery alters in-vivo coagulation and whether any specific alteration influences the development of postoperative thrombosis are unknown. This study compared the concentrations of activated factor VII (FVIIa), tissue factor pathway inhibitor (TFPI), activated factor X (FXa)-TFPI, thrombin-antithrombin, and prothrombin fragment 1+2 (F1+2) in plasmas of 535 healthy individuals (ages 17-76) with those in the preoperative plasmas of 306 arthritis patients (ages 30-92) scheduled for elective knee or hip replacement surgery. C-reactive protein was also measured in the plasmas of approximately 15% of the participants. Age-adjusted concentrations of FVIIa, F1+2, and C-reactive protein were higher in patients than controls, while the concentrations of thrombin-antithrombin, TFPI and FXa-TFPI were similar. Chronic inflammation in the patients was thus associated with increased coagulation in vivo. Without compensatory increases in the concentrations of TFPI (natural inhibitor of prothrombinase), the elevated concentrations of FVIIa in the preoperative plasmas and the trauma associated with surgery may enhance the risk for developing postoperative deep-vein thrombosis.