On Target

ON TARGET
COMPLIMENTARY NEWS LETTER OF TARGET HEALTH® INC.

27 April 2008

I. WHAT'S NEW?
DIA Annual Meeting
II. QUIZ - (Fill In The Blanks)
Anesthesia & Alzheimer’s Disease
III. HISTORY OF MEDICINE
Ancient Biblical & Historical Hospital
IV. INFECTIOUS DISEASE
NIAID Research Priorities To Fight Drug-Resistant Tuberculosis (TB)
V. ONCOLOGY
Weekly Paclitaxel in the Adjuvant Treatment of Breast Cancer
VI. CARDIOLOGY
Drug-Eluting Stents Reduce the Risks For Cardiovascular Events
VII. REGULATORY AFFAIRS
FDA Approves First Compact Heart Assist Device
VIII. TARGET HEALTH

I. WHAT'S NEW?

DIA Annual Meeting

This year we are expanding our booth to better serve our clients. We have added a few couches so we can sit and talk about your needs in a comfortable and relaxed environment. We will showcase our full CRO services including our software toolbox to facilitate drug development. This is the year that Target Health goes paperless. Let us show you what we have done. More details to follow.

Let us know if you will be attending.

For more information about Target Health or any of our software tools for clinical research, please contact Dr. Jules T. Mitchel or Ms. Joyce Hays. Please visit our Website and Blog.

II. QUIZ (Fill In The Blanks)

Anesthesia & Alzheimer’s Disease

In studies of human 1) ___ cells, the widely-used anesthetic desflurane does not contribute to increased production of amyloid-beta protein. However, when combined with low oxygen conditions, it can produce more of this Alzheimer's associated protein. Over 200 million people undergo surgery each year, and there has been concern that anesthetic use may contribute to 2) ___ disease and other brain disorders. Research presented, at the American Society for Biochemistry and Molecular Biology, examined this possibility with commonly used inhalation 3) ___ isoflurane and desflurane. The research team subjected human brain cells to 12% desflurane for six hours (mimicking a surgery condition) and observed no changes in either the production of amyloid-beta 4) ___ or the rate of cell death. However, when combined with low 5) ___ levels (18%), desflurane could stimulate these cellular changes associated with Alzheimer's disease. 6) ___ by itself did not induce any changes. The results with desflurane are contrary to the researchers' previous work, which found isoflurane by itself could stimulate both amyloid production and cell death. The study authors emphasized that the current findings are from cell culture experiments, and the next critical step will be to confirm these findings in animal models and to test the effects of other anesthetic agents. These early results suggest that it is important to ensure that patients undergoing anesthesia maintain sufficient oxygen in their brain.

ANSWERS: 1) brain; 2) Alzheimer’s; 3) anesthetics; 4) protein; 5) oxygen; 6) Hypoxia

III. HISTORY OF MEDICINE

Ancient Biblical & Historical Hospital

The Muristan (Persian for "Hospital") is a complex of streets and shops in the Christian Quarter of the Old City of Jerusalem. The area just south of the Church of the Holy Sepulchre has a long hospitaller tradition dating, according to legend, to the days of Judas Maccabaeus (2nd century BCE). The legend is based on incidents recorded in the Second Book of Maccabees. The legend maintains that King Antiochus proceeded to Jerusalem to punish the High Priest for plundering the Tomb of David. While on Golgotha, the king was directed in a divine vision to pardon the High Priest, and to build a hospital for the care of the sick and poor on that spot. The legend assumed a historical form after 1496 when William Caoursin, Vice-Chancellor of the Hospitallers, records Judas Maccabaeus and John Hyrcanus as the founders of the hospital on that spot.The earliest historical mention of the location is in 600 CE, when a certain Abbot Probus was commissioned by Pope Gregory the Great to build a hospital in Jerusalem to treat and care for Christian pilgrims to the Holy Land. This hospice was most likely destroyed about 14 years later when Jerusalem fell to the Persian army, the Christian inhabitants were slaughtered, and their churches and monasteries destroyed. The building was probably restored after Jerusalem fell again under Roman dominion in 629. Arab rule after 637 allowed freedom of worship, and the restored hospital was probably allowed to continue serving its original purpose. Bernard the Monk, who wrote an account of his visit to Jerusalem in 870, mentions a Benedictine hospital close to the Church of the Holy Sepulchre. In 993, Hugh Marquis of Tuscany and his wife endowed the hospice with considerable property in Italy. In 800, Charlemagne, Emperor of the Holy Roman Empire, enlarged the hospital and added a library to it. About 200 years later, in 1005, Caliph Al Hakim destroyed the hospital and a large number of other buildings in Jerusalem. In 1023, merchants from Amalfi and Salerno in Italy were given permission by the Caliph Ali az-Zahir of Egypt to rebuild the hospice, monastery and chapel in Jerusalem. The hospital, which was built on the site of the Monastery of Saint John the Baptist, took in Christian pilgrims traveling to visit the holy sites. To the east of this hospital, separated from it by a lane, a new hospital for women pilgrims was built. Both hospitals remained under the control of the Benedictine Abbot. In 1078, Jerusalem was captured by the Seljuk Turks who reportedly abused the Christian population, forced pilgrims to pay a heavy tax to visit the Holy Places, and even kidnapped the Patriarch of Jerusalem. In spite of the persecution, the Benedictine hospital continued its ministry. Archbishop John of Amalfi records that during his pilgrimage to Jerusalem in 1082, he visited the hospital.

IV. INFECTIOUS DISEASE

NIAID Research Priorities To Fight Drug-Resistant Tuberculosis (TB)

The World Health Organization (WHO) estimates that 500,000 people worldwide have drug-resistant TB-multidrug (MDR TB), and, alarmingly, the frequently fatal extensively drug-resistant (XDR TB) has been detected in 46 countries. Tuberculosis (TB) has long been one of the world's great killers. Factors contributing to the rising tide of drug-resistant TB include:

Lack of routine testing to determine TB drug-sensitivity
Incomplete treatment of people infected with TB-causing bacteria
The epidemic of TB in HIV-infected people
Limited TB research by pharmaceutical companies, resulting in few new anti-TB drugs or other interventions.

To help in the fight against drug-resistant TB, the National Institute of Allergy and Infectious Diseases (NIAID) has formulated an MDR and XDR TB research agenda. A summary of the agenda, authored by NIAID Director Anthony S. Fauci, M.D., and members of the NIAID Tuberculosis Working Group, is now available online in The Journal of Infectious Diseases (2008; DOI: 10.1086/587904). The NIAID research agenda complements domestic and international efforts to prevent and control the spread of MDR and XDR TB. Whereas the WHO's STOP TB Partnership plan emphasizes increased surveillance and control and treatment efforts, the NIAID agenda focuses on biomedical research. The Institute also collaborates with the Centers for Disease Control and Prevention and other NIH Institutes and Centers on TB research efforts in the United States. To prevent the further emergence and spread of MDR and XDR TB, the NIAID agenda identifies areas of biomedical research that are likely to contribute substantially to a global public health response. Building on existing efforts within the international network of TB research, NIAID's priorities include efforts to:

Develop and test reliable technologies to rapidly diagnose TB and to identify drug resistance
Define the most effective use of existing TB therapies and other antibiotics available to treat drug-resistant TB and develop new drugs, particularly to treat MDR and XDR TB
Better understand the basic biology of TB-causing bacteria and their interaction with the human host that underlie the development of drug-resistant TB
Understand the epidemiology of drug-resistant TB
Investigate the various manifestations of TB in adults, children and those with co-infections, including HIV/AIDS
Conduct research to develop new vaccines and other preventive strategies.

V. ONCOLOGY

Weekly Paclitaxel in the Adjuvant Treatment of Breast Cancer

It is always difficult to determine how often to dose patients with cancer. As a result, a study published in the New England Journal of Medicine (2008; 358:1663-1671), was performed to compare the efficacy of two different taxanes, docetaxel and paclitaxel, given either weekly or every 3 weeks, in the adjuvant treatment of breast cancer. The study enrolled 4,950 women with axillary lymph node–positive or high-risk, lymph node–negative breast cancer. After randomization, all patients first received 4 cycles of intravenous doxorubicin and cyclophosphamide at 3-week intervals and were then assigned to intravenous paclitaxel or docetaxel given at 3-week intervals for 4 cycles or at 1-week intervals for 12 cycles. The primary end point was disease-free survival. Results showed that as compared with patients receiving standard therapy (paclitaxel every 3 weeks), the odds ratio for disease-free survival was 1.27 among those receiving weekly paclitaxel (P=0.006), 1.23 among those receiving docetaxel every 3 weeks (P=0.02), and 1.09 among those receiving weekly docetaxel (P=0.29). As compared with standard therapy, weekly paclitaxel was also associated with improved survival (odds ratio, 1.32; P=0.01). An exploratory analysis of a subgroup of patients whose tumors expressed no human epidermal growth factor receptor type 2 protein found similar improvements in disease-free and overall survival with weekly paclitaxel treatment, regardless of hormone-receptor expression. Grade 2, 3, or 4 neuropathy was more frequent with weekly paclitaxel than with paclitaxel every 3 weeks (27% vs. 20%). The authors concluded that weekly paclitaxel after standard adjuvant chemotherapy with doxorubicin and cyclophosphamide improves disease-free and overall survival in women with breast cancer.

VI. CARDIOLOGY

Drug-Eluting Stents Reduce the Risks For Cardiovascular Events

Few studies have compared medium-term outcomes for drug-eluting stents (DES) and bare metal stents, and most are relatively small randomized controlled trials. Furthermore, since the introduction of DES, there has been increased use and duration of use of clopidogrel, statins, and other evidence-based therapies. As a result, a study published in Circulation (2008;117:2071-2078), was performed to compare outcomes for patients who underwent stenting in the eras before and after the introduction of DES. The study included 11,436 patients who received stents between October 1, 2002, and March 31, 2003, and 12,926 patients who underwent stenting between October 1, 2003, and March 31, 2004. All subjects were patients undergoing stenting in all nonfederal hospitals in New York State. Patients were excluded if they had a previous revascularization. Risk factors that were significant predictors of adverse outcomes were used to adjust adverse outcome rates. Death rates, the combined end point of death and myocardial infarction (MI), nonfatal MI requiring readmission, target vessel revascularization, and target lesion revascularization were compared at 2 years. Results showed that patients in the DES era had significantly better risk-adjusted outcomes for death/MI (9.9% versus 10.8%; adjusted hazard ratio, 0.90); nonfatal MI requiring readmission (adjusted hazard ratio, 0.86); target vessel revascularization (11.2% versus 17.9%; adjusted hazard ratio, 0.60); and target lesion revascularization (8.4% versus 14.7%; hazard ratio, 0.55). According to the authors, patients in the DES era experienced lower rates of death/MI, nonfatal MI, target vessel revascularization, and target lesion revascularization, but there were no differences in the rates of death. These improvements are likely a result of increased use of clopidogrel, statins, and dual antiplatelet therapy, in addition to the introduction of DES.

VII. REGULATORY AFFAIRS

TARGET HEALTH excels in Regulatory Affairs and works closely with many of its clients performing all FDA submissions. TARGET HEALTH receives daily updates of new developments at FDA. Each week, highlights of what is going on at FDA are shared to assure that new information is expeditiously made available.

FDA Approves First Compact Heart Assist Device

Heart assist devices are surgically implanted mechanical pumps that help the heart's ventricle do its work of pumping blood to the rest of the body. Previous models were too large to be placed in the upper abdomen of some women and small-sized men. But the Thoratec HeartMate II Left Ventricular Assist System employs a first-of-a-kind design. Instead of the standard pulsatile pump that simulates the action of the heart, the device uses a continuous flow pump that constantly moves blood with a single moving part, a spinning rotor. This allows the device to be slimmed down to a mere three inches in length and a weight of approximately one pound. According to Daniel Schultz, M.D., director of FDA’s Center for Devices and Radiological Health, "The HeartMate II is an important advance in mechanical heart technology and until now, some heart transplant candidates have been underserved due to the large size of previously approved heart assist devices." The device has an electrical cable that powers the blood pump as the pump passes through the patient's skin to an external controller that the patient wears on his or her waist. The controller is powered either by batteries or connected to an electrical power outlet. Blood flow is set through the pump based on the patient's need, and the controller monitors pump performance, sounding alarms if it detects dangerous conditions or a possible malfunction. The system can operate on two external batteries, allowing the patient to move freely for up to three hours. In a clinical study of 126 patients at 26 transplant centers, 57% of patients with the HeartMate II survived to heart transplant, which is comparable to the survival of patients treated with currently approved heart assist devices. The product's manufacturer, Thoratec Corporation of Pleasanton, Calif., is required to conduct a post-approval study to further evaluate the HeartMate II's performance during commercialization.

For more information about our expertise in Regulatory Affairs, please contact Dr. Jules T. Mitchel or Dr. Glen Park.

VIII. TARGET HEALTH

TARGET HEALTH INC. (www.targethealth.com) is a full service eCRO with full-time staff dedicated to all aspects of drug and device development. Areas of expertise include Regulatory Affairs, comprising, but not limited to, IND, IDE, NDA, PMA and 510(k) submissions, execution of Clinical Trials, Project Management, Biostatistics and Data Management, Web Trials, utilizing Target e*CRF®, our proprietary Internet-based Clinical Trial System, and Medical Writing. TARGET HEALTH's Pharmaceutical Advisory Dream Team assists companies in strategic planning from Discovery to Market Launch. Let us help you on your next project.

TARGET HEALTH INC.
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Dr. Jules T. Mitchel, President
Ms Joyce Hays, CEO