On Target

ON TARGET
COMPLIMENTARY NEWS LETTER OF TARGET HEALTH® INC.

13 April 2008

I. WHAT'S NEW?
Why Use Target e*CRF® for EDC Trials
II. QUIZ - (Fill In The Blanks)
Alligator Antibiotics
III. HISTORY OF MEDICINE
Silphium – Herbal Medicine From 650 BC Greece
IV. WOMEN'S HEALTH
Abdominal Adiposity and CVD Risk in Women
V. DIABETES
Aggressive Lowering of BP and Cholesterol Helps in Markers of Heart Disease
VI. PEDIATRICS
Placebo Effects in Migraine Studies in Children and Adolescence
VII. REGULATORY AFFAIRS
Public Health Warning - High Levels of Selenium in "Total Body Formula" and "Total Body Mega Formula"
VIII. TARGET HEALTH

I. WHAT'S NEW?

Why Use Target e*CRF® for EDC Trials

Target Health is constantly asked "why should our company use your EDC software when there are large public companies and/or highly visible companies with private investors who do the same thing?" Here is our response:

We are a full service CRO that develops and uses it's own software for EDC
We have been doing worldwide EDC since 1999 with over 125 studies from Phase 1 to Phase 4
There are 14 approved products on the market that used Target e*CRF® for the pivotal trials (2-NDAs, 10-PMAs, 1-510(k)
There are 3 products currently in review by FDA that used Target e*CRF® for the pivotal trials (2 NDAs, 1 PMA)
There are 1 product currently in review by EMEA that used Target e*CRF® for the pivotal trials
There are 4 International approvals (2 in Canada and 2 in Europe)
We can usually build a study and release it in less than 4 weeks and quicker, if necessary
Batch edit checks are run through the query system by the CRAs, by site
Our software requires minimal training, therefore minimal help desk
We have the best service in the industry - most changes take less than 1 day from request to release
All programmers are based in our offices Manhattan
Loyal customer base
Just ask any of our clients
We offer the best prices since we do not need to satisfy the investment community
We will match any bona fide EDC bid with a 20% discount

For more information about Target e*CRF® or any of our software tools for clinical research, please contact Dr. Jules T. Mitchel or Joyce Hays. For other new business opportunities, contact Dr. Jules T. Mitchel . Please visit our Website and Blog.

II. QUIZ (Fill In The Blanks)

Alligator Antibiotics

New antibiotics may be discovered in alligator 1) ___. Scientists are zeroing in on snippets of 2) ___ found in American alligator blood that kill a wide range of disease-causing 3) ___, including the formidable MRSA or methicillin-resistant Staphylococcus aureus. Previous experiments have revealed that alligator blood extract cripples many human 4) ___, including E. coli, herpes simplex virus and some strains of the yeast Candida albicans. The serum's antimicrobial power probably derives from protein bits called peptides. Several such germ-fighting peptides, widespread among reptiles and amphibians, have been isolated from the skin of frogs in recent years. Many of these animals live in polluted areas, and alligators probably eat, among other things, diseased animals. Fierce battles with prey and other alligators can leave gaping flesh wounds in an alligator - but the animals are fairly hardy. These 5) ___ provide a first line of defense which is important in the lower vertebrates, who have a slower antibody response than humans. In order to survive, these primordial creatures have developed a circulating system that creates 6) ___, that protect them. Also, interesting is that because of their special immune responses, alligators rarely develop tumors. However, these creatures are by no means immune to all diseases. Recently, an epidemic caused by mycoplasma, the bacterial group responsible for 7) ___, swept through a ‘gator farm in Florida. Thirty-three died and 13 more were euthanized. Later the bacteria was dubbed Mycoplasma alligatoris.

ANSWERS: 1) blood; 2) proteins; 3) microbes; 4) pathogens; 5) peptides; 6) antimicrobials; 7) pneumonia

III. HISTORY OF MEDICINE

Silphium – Herbal Medicine From 650 BC Greece

Silphium (also known as silphion or laser) was a plant of the genus Ferula. Generally considered to be extinct, it once formed the crux of trade from the ancient city of Cyrene for its use as a rich seasoning and as a medicine. It was so critical to the Cyrenian economy that most of their coins bore a picture of the plant. Silphium was an important species in prehistory, as evidenced by the Egyptians and Knossos Minoans developing a specific glyph, or pictograph, to represent the Silphium plant. The valuable product was the resin of the plant. It was harvested in a manner similar to asafoetida, a plant with similar enough qualities to silphium that Romans, including the geographer Strabo, used the same word to describe both. Aside from its uses in Greco-Roman cooking (as in recipes by Apicius), many medical uses were ascribed to the plant. It was said that it could be used to treat cough, sore throat, fever, indigestion, aches and pains, warts, and all kinds of maladies. Chief among its medical uses, according to Pliny the Elder, was its role as a herbal contraceptive. Given that many species in the parsley family have estrogenic properties, and some (such as Wild carrot) have been found to work as an abortifacient, it is quite possible that the plant was pharmacologically active in the prevention or termination of pregnancy. Legend said that it was a gift from the god Apollo. It was used widely by most ancient Mediterranean cultures; the Romans considered it "worth its weight in denarii." There was widespread use of silphium in ancient Egypt for birth control. The reason for silphium's extinction is not entirely known. The plant grew along a narrow coastal area, about 125 by 35 miles, in Cyrenaica, one of the five great Greek cities around 650 BC (in present-day Libya). Much of the speculation about the cause of its extinction rests on a sudden demand for animals that grazed on the plant, for some supposed effect on the quality of the meat. Overgrazing combined with overharvesting may have led to its extinction. The climate of the maghreb has been drying over the millennia, and desertification may also have been a factor. Another theory is that when Roman provincial governors took over power from Greek colonists, they over-farmed silphium and rendered the soil unable to yield the type that was said to be of such medicinal value. Pliny reported that the last known stalk of silphium was given to the Emperor Nero "as a curiosity".

IV. WOMEN'S HEALTH

Abdominal Adiposity and CVD Risk in Women

Accumulating evidence indicates that abdominal adiposity is positively related to cardiovascular disease (CVD) risk and some other diseases independently of overall adiposity. However, the association of premature death resulting from these diseases with abdominal adiposity has not been widely studied, and findings are inconsistent. As a result, a study published in the journal Circulation (2008;117:1658 – 1667) examined the associations of abdominal adiposity with all-cause and cause-specific mortality. The study showed that women who carry excess fat around their waists were at greater risk of dying early from cancer or heart disease than were women with smaller waistlines, even if they were of normal weight. The investigation was a prospective cohort study of 44,636 women in the Nurses’ Health Study (NHS). The NHS has been following the health history of thousands of registered nurses in 11 states. All the women included in the study were registered nurses. At the beginning of the study the women were asked to measure their waists and hips. Every two years, the women completed questionnaires about their health, providing information about their age, activity level, smoking status, diet, blood pressure and cholesterol levels. During 16 years of follow-up, 3507 deaths were identified, including 751 cardiovascular deaths and 1748 cancer deaths. Results showed that women with greater waist circumferences were more likely to die prematurely, particularly from heart disease, when compared to women with smaller waists. For example, women with waist size equal to or greater than 35 inches were approximately twice as likely to die of heart disease as were women with a waist size less than 28 inches, regardless of their body mass index. Similarly, women with a waist size equal to or greater than 35 inches also were twice as likely to die of cancer as were women with a waist size less than 28 inches. Women who had a greater waist circumference and were also obese were at the greatest risk of premature death. It was also determined if a woman was overweight by calculating her body mass index (BMI), a measure of a person's weight in relation to height. BMI is used to estimate the proportion of a person's weight that derives from body fat. A BMI between 18.5 and 24.9 is considered healthy. A BMI of 30.0 - 39.9 is regarded as overweight. It was concluded that anthropometric measures of abdominal adiposity were strongly and positively associated with all-cause, CVD, and cancer mortality independently of body mass index, and that elevated waist circumference was associated with significantly increased CVD mortality even among normal-weight women.

V. DIABETES

Aggressive Lowering of BP and Cholesterol Helps in Markers of Heart Disease

An estimated 21 million Americans have diabetes and 284,000 die from it each year. Sixty five percent of the deaths are related to cardiovascular disease (CVD). American Indians have a high rate of diabetes and cardiovascular disease related to diabetes, but there are few clinical trials that address these issues in this population. As a result, a study published in the Journal of the American Medical Association (299:1678-1689) was performed to compare progression of sub clinical atherosclerosis in American Indian adults with type 2 diabetes treated to reach aggressive targets of low-density lipoprotein cholesterol (LDL-C) of 70 mg/dL or lower and systolic blood pressure (SBP) of 115 mm Hg or lower. Atherosclerosis (i.e. hardening of the arteries) is the number one cause of heart disease and can lead to heart attack, stroke, and death. The study was a randomized, open-label, 3-year clinical trial which included 499 men and women aged 40 years or older with type 2 diabetes and no prior CVD events. For the study, known as the “Stop Atherosclerosis in Native Diabetics Study (SANDS)”, participants were randomized to aggressive (n=252) vs. standard (n=247) treatment groups with stepped treatment algorithms defined for both. Participants were also encouraged to follow lifestyle approaches to help meet their blood pressure and cholesterol treatment targets, such as following a heart-healthy eating plan, being physically active, maintaining a healthy weight, and not smoking. To assess the impact of the treatments on the participants' cardiovascular health, the study used ultrasound to measure the thickness of the carotid (neck) artery - an indication of hardening of the arteries, a leading effect of high blood pressure and cholesterol and an early sign of CVD. In addition, ultrasound was also used to measure the size and function of the left ventricle, the heart's main pumping chamber. Enlarged hearts are known to be predictors of increased risk of heart attack and stroke. These measurements were taken at enrollment, at 18 months, and at 36 months. Results showed that mean target LDL-C and SBP levels for both groups were reached and maintained. Compared with baseline, the carotid artery thickness regressed in the aggressive group and progressed in the standard group (–0.012 mm vs 0.038 mm; P < .001); carotid arterial cross-sectional area also regressed (–0.02 mm2 vs 1.05 mm2; P < .001); and there was greater decrease in left ventricular mass index (–2.4 g/m2.7 vs –1.2 g/m2.7; P = .03) in the aggressive group. Rates of adverse events (38.5% and 26.7%; P = .005) and serious adverse events (n = 4 vs 1; P = .18) related to blood pressure medications were higher in the aggressive group. Clinical CVD events (1.6/100 and 1.5/100 person-years) did not differ significantly between groups. According to the authors, aggressively lowering cholesterol and blood pressure levels below current targets in adults with type 2 diabetes may help to prevent -- and possibly reverse -- hardening of the arteries. Since clinical events were lower than expected and did not differ significantly between groups, further follow-up is needed to determine whether these improvements will result in lower long-term CVD event rates and costs and favorable risk-benefit outcomes.

VI. PEDIATRICS

Placebo Effects in Migraine Studies in Children and Adolescence

According to an article published in the Journal of Pediatrics (2008;152:527-533), a study was performed to characterize the magnitude of the placebo response in trials of migraine therapy in children and adolescents, and to identify its determinants. For the study, the MEDLINE and CENTRAL databases were searched through November 2006 for randomized controlled trials or controlled clinical trials of pediatric acute migraine pharmacologic treatment that included a placebo comparator group. A total of 13 trials (1,324 participants in the placebo groups) were included in the analysis. The main outcomes were headache relief and pain-free response. The influence of the causes of the placebo response was studied using subgroup analysis. Results showed that the pooled placebo responses for pain relief was 46% (range, 38% to 53%) and pain-free at 2 hours 21% (range, 17% to 26%). Parallel studies conducted in North American centers demonstrated a significantly higher placebo response, as did trials that used 4-point pain scales. According to the authors, the widely variable placebo response in pediatric migraine trials, supports the continued use of placebo groups and suggested the need for more research into the placebo effect in the pediatric population.

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.

Public Health Warning - High Levels of Selenium in "Total Body Formula" and "Total Body Mega Formula"

Selenium, a naturally occurring mineral that can boost the immune system, is needed only in very small amounts for good health. Generally, normal consumption of food and water provides adequate selenium to support good health. Excessive intake of selenium is known to cause symptoms to include significant hair loss, muscle cramps, diarrhea, joint pain, fatigue, loss of finger nails and blistering skin. The FDA has announced today that it has found hazardous levels of selenium in samples of certain flavors of the dietary supplement products "Total Body Formula" and "Total Body Mega Formula" distributed by Total Body Essential Nutrition of Atlanta. FDA is advising consumers to stop using "Total Body Formula" in flavors Tropical Orange and Peach Nectar and "Total Body Mega Formula" in the Orange/Tangerine flavor and discard them by placing them in a trash receptacle outside of the home. FDA has received 43 reports of persons from nine states (Alabama, Florida, Georgia, Kentucky, Michigan, New Jersey, North Carolina, Tennessee, and Texas) who experienced serious adverse reactions using these products. On March 27, FDA initially warned consumers not to purchase these products www.fda.gov/bbs/topics/NEWS/2008/NEW01812.html. The adverse reactions generally occurred after five to 10 days of daily ingestion of the product, and included significant hair loss, muscle cramps, diarrhea, joint pain, deformed fingernails, and fatigue. Analyses of samples of the products by FDA laboratories have now found most of the samples contain extremely high levels of selenium--up to 40,800 micrograms per recommended serving, or more than 200 times the amount of selenium per serving (i.e., 200 micrograms) indicated on the labels of the products. The FDA continues to investigate the matter to determine how excessive amounts of selenium were added to the products.

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.
261 Madison Avenue
24th Floor
New York, NY 10016
Phone: (212) 681-2100; Fax (212) 681-2105

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www.targethealth.com
Dr. Jules T. Mitchel, President
Ms Joyce Hays, CEO