Gene Barnett

Phase III randomized trial of CED of IL13-PE38QQR vs Gliadel wafers for recurrent glioblastoma †

Convection-enhanced delivery (CED) of cintredekin besudotox (CB) was compared with Gliadel wafers (GW) in adult patients with glioblastoma multiforme (GBM) at first recurrence. Patients were randomized 2:1 to receive CB or GW. CB (0.5 microg/mL; total flow rate 0.75 mL/h) was administered over 96 hours via 2-4 intraparenchymal catheters placed after tumor resection. GW (3.85%/7.7 mg carmustine per wafer; maximum 8 wafers) were placed immediately after tumor resection. The primary endpoint was overall survival from the time of randomization. Prestated interim analyses were built into the study design. Secondary and tertiary endpoints were safety and health-related quality-of-life assessments. From March 2004 to December 2005, 296 patients were enrolled at 52 centers. Demographic and baseline characteristics were balanced between the 2 treatment arms. Median survival was 36.4 weeks (9.1 months) for CB and 35.3 weeks (8.8 months) for GW (P = .476). For the efficacy evaluable population, the median survival was 45.3 weeks (11.3 months) for CB and 39.8 weeks (10 months) for GW (P = .310). The adverse-events profile was similar in both arms, except that pulmonary embolism was higher in the CB arm (8% vs 1%, P = .014). This is the first randomized phase III evaluation of an agent administered via CED and the first with an active comparator in GBM patients. There was no survival difference between CB administered via CED and GW. Drug distribution was not assessed and may be crucial for evaluating future CED-based therapeutics.

COSTAR—A computer-based medical information system for ambulatory care

The storage, retrieval, and communication of information are key features of both the practice of medicine and the administration of health care. This paper describes a COmputer-STored Ambulatory Record (COSTAR) which replaces the traditional document-based patient medical record with a comprehensive, centralized, and integrated information system. COSTAR meets both the medical care and the financial/administrative needs of a variety of different medical practices (whether fee-for-service or prepaid) and can be implemented and operated without on-site programming support. COSTAR has a modular design to facilitate phased implementation, and uses a comprehensive dictionary of terms to standardize and store data. The physician records medical, administrative, and financial information on a single source document (the encounter form); data are input by clerical personnel; information is retrieved via different computer-generated displays and printouts which automatically select and organize the data. The system provides a High-level language which allows the user to access the database from a logical point of view and perform searches or prepare reports without programming support. COSTAR is available on minicomputers using commercially supported software and will be marketed by commercial organizations.

Just-in-time clinical information.

The just-in-time (JIT) model originated in the manufacturing industry as a way to manage parts inventories process so that specific components could be made available at the appropriate times (that is, “just in time”). This JIT model can be applied to the management of clinical information inventories, so that clinicians can have more immediate access to the most current and relevant information at the time they most need it--when making clinical care decisions. The authors discuss traditional modes of managing clinical information, and then describe how a new, JIT model may be developed and implemented. They describe three modes of clinician-information interactions that a JIT model might employ, the scope of information that may be made available in a JIT model (global information or local, case-specific information), and the challenges posed by the implementation of such an information-access model. Finally, they discuss how JIT information access may change how physicians practice medicine, various ways JIT information may be delivered, and concerns about the trustworthiness of electronically published and accessed information resources.

Chronic thalamic stimulation for the tremor of multiple sclerosis

Article abstract The authors studied chronic high-frequency stimulation of the ventral intermediate nucleus of the thalamus (Vim) for controlling upper extremity tremor in patients with MS using MRI, CT, and microelectrode recordings and stimulation to locate optimal target sites. Fifteen patients underwent surgery. All patients had reduced tremor but developed tolerance requiring repeated programming of the stimulator. Benefit at optimal stimulator settings was maintained. Two patients experienced complications: intracerebral hematoma and MS exacerbation. Chronic high-frequency stimulation of Vim provides tremor reduction if patients have access to frequent stimulator adjustments. This surgery is relatively safe.

Glioblastomas Induce T-Lymphocyte Death by Two Distinct Pathways Involving Gangliosides and CD70

Here we report that glioblastoma multiforme (GBM) mediates immunosuppression by promoting T-cell death via tumor-associated CD70 and gangliosides that act through receptor-dependent and receptor-independent pathways, respectively. GBM lines cocultured with T cells induced lymphocyte death. The GBM lines were characterized for their expression of CD70, Fas ligand (FasL), and tumor necrosis factor-alpha (TNF-alpha), and the possible participation of those molecules in T-cell killing was assessed by doing GBM/T cell cocultures in the presence of anti-CD70 antibodies, Fas fusion proteins, or anti-TNF-alpha antibodies. CD70 but not TNF-alpha or FasL is responsible for initiating T-cell death via the receptor-dependent pathway. Of the four GBM cell lines that induced T-cell death, three highly expressed CD70. Two nonapoptogenic GBM lines (CCF3 and U138), on the other hand, had only minimally detectable CD70 expression. Blocking experiments with the anti-CD70 antibody confirmed that elevated CD70 levels were involved in the apoptogenicity of the three GBM lines expressing that molecule. Gangliosides were found to participate in the induction of T-cell apoptosis, because the glucosylceramide synthase inhibitor (PPPP) significantly reduced the abilities of all four apoptogenic lines to kill the lymphocytes. High-performance liquid chromatography (HPLC) and mass spectroscopy revealed that GM2, GM2-like gangliosides, and GD1a were synthesized in abundance by all four apoptogenic GBM lines but not by the two GBMs lacking activity. Furthermore, gangliosides isolated from GBM lines as well as HPLC fractions containing GM2 and GD1a were directly apoptogenic for T cells. Our results indicate that CD70 and gangliosides are both products synthesized by GBMs that may be key mediators of T-cell apoptosis and likely contribute to the T-cell dysfunction observed within the tumor microenvironment.

The Influence of Scalp Infiltration with Bupivacaine on Hemodynamics and Postoperative Pain in Adult Patients Undergoing Craniotomy

After craniotomy, hypertension may contribute to intracerebral hemorrhage.We studied whether scalp infiltration with bupivacaine during craniotomy reduces postoperative pain and hypertension. In a double-blind fashion, 36 adult patients (ASA physical status II or III) undergoing elective craniotomy were randomly assigned to receive scalp infiltration with either bupivacaine (0.25%) and epinephrine (1:200,000) or saline/epinephrine (1:200,000) for skeletal fixation, skin incision, and wound closure. Heart rate (HR) and mean arterial pressure (MAP) were measured after anesthesia induction, after skull-pin insertion, after scalp infiltration, during dural closure, during skin closure, on admission to postanesthesia care unit (PACU), and 1 h after admission. Visual analog pain scores were recorded in the PACU. MAP was significantly greater in the saline group at scalp infiltration. HR was significantly faster in the saline group at dural and skin closure. The bupivacaine group reported significantly less pain than the saline group at PACU admission and 1 h after admission. Pain scores did not correlate with hemodynamic measurements. We conclude that scalp infiltration with 0.25% bupivacaine with 1:200,000 epinephrine blunts certain intraoperative hemodynamic responses and reduces postoperative pain but has no effect on postoperative hemodynamics. Implications: We sought to evaluate whether scalp infiltration with bupivacaine and epinephrine at the beginning and end of craniotomy would afford more intra- and postoperative hemodynamic stability and influence immediate postoperative pain. We found that intraoperative hemodynamics were not influenced greatly; however, craniotomy patients do have significant postoperative pain, which does not seem to have an influence on hemodynamics in the postanesthesia care unit. (Anesth Analg 1998;87:579-82)

Recording, Retrieval and Review of Medical Data by Physician-Computer Interaction

Abstract A computer-based medical-record system depending on a dialogue between the physician and a computer-controlled display screen has been designed to enter progress notes. A limited vocabular...

Computers in Patient Care

IN most areas of medical care, adaptations in practice have kept pace with advances in knowledge about diseases and therapeutic procedures. However, one vital area of medical practice, information ...

Limitations of provider interventions in hypertension quality assurance.

In an institutional quality assurance program in hypertension, performance of tests, control of blood pressure, and follow-up were monitored through a computer program that was developed to audit records in an automated record system. Two types of feedback previously shown to be effective were provided quarterly for a period of one year to experimental providers. For all hypertensives considered together, there were no differences between scores of Experimental and Control providers based on percentage of patients meeting pre-set criteria in testing--87% vs 87%--, blood pressure control--58% vs 59%--, or follow-up--79% vs 77%. Only small but significant differences occurred in the subgroup of moderate to severe hypertensives. There appear to be limitations to what can be accomplished through hypertension quality assurance interventions directed at providers of care in this institutional setting. Interventions designed to deal directly with patients whose blood pressures are uncontrolled may be more effective.

An on-line computer facility for systematized input of radiology reports.

Stimulated by both the increased demand for medical care and the rapid growth of medical knowledge, the practice of medicine today, in both small and large medical centers, is involved with fragments of information from a variety of sources. As the patient load grows and the number and variety of tests, procedures, examinations, consultations, etc., increase, it becomes more difficult to manage the large amount of pertinent information accumulated on a single patient. The need for improved information-processing, especially in large medical centers, is increasingly evident. Hospitals have little or no documentation of the cost of their present information-processing technics, but it has been estimated that it may be as much as 25 per cent of a total hospital operating budget (1). The costs are usually not visible, however, and the direct and indirect development and utilization costs of automated information processing are often difficult to justify on economical considerations alone. Presumably better pa...