Prospective randomized trial of hepatic artery chemotherapy with cisplatin and doxorubicin, with or without lipiodol in the treatment of advanced stage hepatocellular carcinoma.

PURPOSE: This randomized study assessed the responses in hepatocellular carcinoma (HCC) to hepatic arterial doxorubicin plus cisplatin, with or without lipiodol. PATIENTS AND METHODS: Patients with unresectable and biopsy-proven HCC were treated with doxorubicin (30 mg/m) plus cisplatin (100 mg/m) without (Solution) or with (Lipiodol) emulsification every 2 months till tumor progression. Primary end point was response. RESULTS: Partial response rate was 56.8% for Lipiodol and 47% for Solution, P=0.48. Responses were evaluated as tumor size changes without vascularity assessments, due to the lipiodol. There were no complete responses. Survival at 6,12,18, and 24 months was 65, 32, 27, and 10.8% for Lipiodol patients and 70.6, 26.6, 8.8, and 8.8 for Solution patients. Of the total 71 enrolled and evaluable patients, survival at 6, 12, and 18 months was 75.7, 40, and 35% for responders and 58.8, 17.6, and 0 for nonresponders. There were no clear clinical or biochemical profile differences between the 2 treatment groups or between responders and nonresponders. CONCLUSIONS: Lipiodol conferred a minor response advantage, recorded as tumor size change, to hepatic arterial chemotherapy with doxorubicin plus cisplatin for HCC, but no survival advantage.

Evaluation of prescribing practices: risk of lactic acidosis with metformin therapy.

BACKGROUND: The risk of lactic acidosis during metformin therapy is linked to specific and well-documented conditions that constitute contraindications or precautions to use of the agent. We conducted a retrospective evaluation of metformin use to determine whether prescribing practices are in accord with published contraindications and precautions. METHODS: All patients admitted to the hospital during a 6-month period who received at least 1 dose of metformin were identified through hospital pharmacy records. Patient demographics and clinical characteristics were then evaluated to determine whether metformin was prescribed to patients possessing any of the risk factors associated with development of lactic acidosis. RESULTS: We identified 263 hospitalizations involving 204 patients who received at least 1 dose of metformin during inpatient admission. Patients had at least 1 absolute contraindication to metformin therapy in 71 admissions (27%). In 29 (41%) of these 71 admissions, treatment with metformin continued despite the contraindication. The most common contraindication, elevated serum creatinine concentration, was present or developed during 32 admissions (12%); however, metformin use was appropriately discontinued in only 8 (25%) of these 32 patients. Of the precautions against metformin use, concomitant administration of cationic agents was the most common, occurring in 97 admissions (37%). CONCLUSIONS: Many patients are treated with metformin despite having clinical conditions that place them at risk for developing lactic acidosis. To minimize this risk, it is essential that prescribers develop a better understanding of the prescribing guidelines for metformin.

Collaborative approach in the development of high-performance brain-computer interfaces for a neuroprosthetic arm: translation from animal models to human control.

Our research group recently demonstrated that a person with tetraplegia could use a brain-computer interface (BCI) to control a sophisticated anthropomorphic robotic arm with skill and speed approaching that of an able-bodied person. This multiyear study exemplifies important principles in translating research from foundational theory and animal experiments into a clinical study. We present a roadmap that may serve as an example for other areas of clinical device research as well as an update on study results. Prior to conducting a multiyear clinical trial, years of animal research preceded BCI testing in an epilepsy monitoring unit, and then in a short-term (28 days) clinical investigation. Scientists and engineers developed the necessary robotic and surgical hardware, software environment, data analysis techniques, and training paradigms. Coordination among researchers, funding institutes, and regulatory bodies ensured that the study would provide valuable scientific information in a safe environment for the study participant. Finally, clinicians from neurosurgery, anesthesiology, physiatry, psychology, and occupational therapy all worked in a multidisciplinary team along with the other researchers to conduct a multiyear BCI clinical study. This teamwork and coordination can be used as a model for others attempting to translate basic science into real-world clinical situations.

A multidisciplinary approach to honest broker services for tissue banks and clinical data: a pragmatic and practical model.

BACKGROUND: Honest broker services are essential for tissue- and data-based research. The honest broker provides a firewall between clinical and research activities. Clinical information is stripped of Health Insurance Portability and Accountability Act-denoted personal health identifiers. Research material may have linkage codes, precluding the identification of patients to researchers. The honest broker provides data derived from clinical and research sources. These data are for research use only, and there are rules in place that prohibit reidentification. Very rarely, the institutional review board (IRB) may allow recontact and develop a recontact plan with the honest broker. Certain databases are structured to serve a clinical and research function and incorporate 'real-time' updating of information. This complex process needs resolution of a variety of issues regarding the precise role of the HB and their interaction with data. There also is an obvious need for software solutions to make the task of deidentification easier. METHODS: The University of Pittsburgh has implemented a novel, IRB-approved mechanism to address honest broker functions to meet the specimen and data needs of researchers. The Tissue Bank stores biologic specimens. The Cancer Registry culls data and annotating information as part of state- and federal-mandated functions and collects data on the clinical progression, treatment, and outcomes of cancer patients. The Cancer Registry also has additional IRB approval to collect data elements only for research purposes. The Clinical Outcomes Group is involved in patient safety and health services research. Radiation Oncology and Medical Oncology provide critical treatment related information. Pathology and Oncology Informatics have designed software tools for querying availability of specimens, extracting data, and deidentifying specimens and annotating data for clinical and translational research. These entities partnered and submitted a joint IRB proposal to create an institutional honest broker facility. The employees of this conglomerate have honest broker agreements with the University of Pittsburgh and the Medical Center. This provides a large group of honest brokers, ensuring availability for projects without any conflict of interest. RESULTS: The honest broker system has been an IRB-approved institutional entity at the University of Pittsburgh since 2003. The honest broker system currently includes 33 certified honest brokers encompassing the multiple partners of this system. The honest broker system has handled >1600 requests over the past 4 years with a 25% increase in volume each year. CONCLUSIONS: The current results indicate that the collaborative honest broker model described herein is robust and provides a highly functional solution to the specimen and data needs for critical clinical and translational research activities.

Explanations and unresolved issues pertaining to the development of the Nuclear Pharmacy Compounding Guidelines.

OBJECTIVES: To provide background information related to the development of the Nuclear Pharmacy Compounding Guidelines, to discuss regulatory complexities related to radiopharmaceutical compounding practice, and to summarize the gaps in the current compounding regulations for radiopharmaceuticals. DATA SOURCES: The Guidelines closely follow the provisions of section 503A of the Federal Food, Drug, and Cosmetic Act (FD&C Act), the monographs and chapters related to pharmacy compounding in the United States Pharmacopeia (USP), and the recommended guidelines published by the American Society of Health-System Pharmacists. SUMMARY: The Food and Drug Administration Modernization Act (FDAMA) of 1997 established parameters under which the compounding of drug products is appropriate and lawful, but these criteria expressly do not apply to radiopharmaceuticals. The Nuclear Pharmacy Compounding Practice Committee, a group of nuclear pharmacists convened by the American Pharmaceutical Association, developed the Nuclear Pharmacy Compounding Guidelines to establish a set of principles and guidelines for good radiopharmaceutical compounding practice. The intent of the new document is to provide guidance on radiopharmaceutical compounding practices that have evolved over the last 2 decades and to place them in an appropriate regulatory framework in accordance with previous enforcement policies and guidelines issued by the U.S. Food and Drug Administration (FDA) regarding the exemption of certain pharmacy practices from enforcement of adulteration, misbranding, and new drug requirements. CONCLUSION: The Nuclear Pharmacy Compounding Guidelines, recently released by APhA, is the first official document that provides realistic and practical compounding guidance for nuclear pharmacists. Even though the United States Court of Appeals for the Ninth Circuit recently ruled section 503A of the FD&C Act to be invalid in its entirety, and the Supreme Court upheld that ruling, the compliance policy guides issued by FDA in March 1992 and revised in May 2002 maintain guiding principles on pharmacy compounding similar to those stated in section 503A of the FD&C Act. The Nuclear Pharmacy Compounding Practice Committee is optimistic that the practical information contained in the Guidelines will assist state boards of pharmacy, FDA, and the United States Pharmacopeial Convention in setting appropriate standards for nuclear pharmacy compounding practice that will ensure the continued availability of high-quality compounded radiopharmaceuticals at reasonable cost.