Peter A. Gross

Phase I Trial of Intravenous Administration of PV701, an Oncolytic Virus, in Patients With Advanced Solid Cancers

PURPOSE PV701, a replication-competent strain of Newcastle disease virus, causes regression of tumor xenografts after intravenous administration. This phase I study was designed to define the maximum-tolerated dose (MTD) and safety of single and multiple intravenous doses of PV701 as a single agent in patients with cancer. PATIENTS AND METHODS Seventy-nine patients with advanced solid cancers that were unresponsive to standard therapy were enrolled. Four PV701 intravenous dosing regimens were evaluated: (1) single dose: one dose every 28 days; (2) repeat dose: three doses in 1 week every 28 days; (3) desensitizing: one lower dose followed by two higher doses in 1 week every 28 days; and (4) two week: one lower dose followed by five higher doses over 2 weeks every 21 days. RESULTS A 100-fold dose intensification was achieved over 195 cycles. A first-dose MTD of 12 x 10(9) plaque-forming units (PFU)/m(2) was established for outpatient dosing. After an initial dose of 12 x 10(9) PFU/m(2), patients tolerated an MTD for subsequent doses of 120 x 10(9) PFU/m(2). The most common adverse events were flu-like symptoms that occurred principally after the first dose and were decreased in number and severity with each subsequent dose. Tumor site-specific adverse events and acute dosing reactions were also observed but not cumulative toxicity. Objective responses occurred at higher dose levels, and progression-free survival ranged from 4 to 31 months. Tumor tissue from one patient was obtained after 11 months of therapy and showed evidence of PV701 particles budding from the tumor cell membrane by electron microscopy and a pronounced lymphoplasmacytic infiltrate by histologic examination. CONCLUSION PV701 warrants further study as a novel therapeutic agent for cancer patients.

Observations on Mortality during the 1918 Influenza Pandemic

The original purpose of our study was to examine the unusual W-shaped mortality curve associated with the 1918 influenza pandemic and possibly explain the peak in mortality among individuals aged 20-40 years. We plotted age-specific excess mortality instead of total mortality for the 1918 pandemic using a 5-year baseline. For comparison, we also graphed excess mortality curves for the 1957 and 1968 pandemics using 5-year baselines. The 1957 and 1968 curves exhibited the usual U-shaped curve, with high excess mortality among infants and the elderly population relative to young adults. The 1918 curve, however, presented unexpected results. A peak in excess mortality among infants and young adults was seen, but the expected W shape did not result. We instead found negative excess mortality among elderly individuals, suggesting that this group was exposed, at an earlier date, to an influenza strain similar to the so-called Spanish influenza (H1N1) strain.

A Pragmatic Approach to Implementing Best Practices for Clinical Decision Support Systems in Computerized Provider Order Entry Systems

Incorporation of clinical decision support (CDS) capabilities is required to realize the greatest benefits from computerized provider order entry (CPOE) systems. Discussions at a conference on CDS in CPOE held in San Francisco, California, June 21-22, 2005 produced several papers in this issue of JAMIA. The first paper reviews CDS for electronic prescribing within CPOE systems; (1) the second describes current controversies regarding creation, maintenance, and uses of CPOE order sets for CDS; (2) and the third presents issues related to certification as a potential means of validating CPOE systems for widespread use. (3) This manuscript summarizes all of the discussions at the meeting and provides a pragmatically oriented view of how to implement CPOE with CDS.

Extending the Nurse Practitioner Concurrent Intervention Model to Community-Acquired Pneumonia and Chronic Obstructive Pulmonary Disease

BACKGROUND A Nurse Practitioner (NP) Concurrent Intervention Model shown effective for controlling telemetry usage was extended to patients with community-acquired pneumonia (CAP) and patients with chronic obstructive pulmonary disease (COPD). METHODS In spring 2000, investigators at Hackensack University Medical Center and the University of Medicine and Dentistry of New Jersey-New Jersey Medical School began an intervention to increase compliance with the Centers for Medicare & Medicaid Services (CMS) performance measures for CAP. Cost-reduction efforts were introduced by using previously described criteria for switching from intravenous to oral medication and for hospital discharge. RESULTS Use of the NP intervention model for patients admitted with CAP and for COPD patients resulted in significant reductions in length of stay and cost savings. DISCUSSION Concurrent intervention by a nurse practitioner can help achieve excellent compliance with performance measures for CAP and be applied to other chronic respiratory diseases such as COPD.

Performance Measures for Guidelines on Preventing Opportunistic Infections in Patients Infected with Human Immunodeficiency Virus

This article serves as a complement to the 1999 US Public Health Service/Infectious Diseases Society of America guidelines on the prevention of opportunistic infections in persons infected with HIV, published in this issue of Clinical Infectious Diseases [1]. A number of performance measures to assess compliance with the guidelines and to aid in their implementation are proposed.