On Target

ON TARGET
COMPLIMENTARY NEWS LETTER OF TARGET HEALTH® INC.

17 February 2008

I. WHAT'S NEW?
Target Health Electronic Tool Box
II. QUIZ - (Fill In The Blanks)
Technique Transforms Millions of Points of Light into 3-D Images
III. HISTORY OF MEDICINE HONORS PRESIDENT'S DAY
Medical Life in Colonial Virginia – George Washington
IV. WOMEN'S HEALTH
Smoking and Risk of Preeclampsia
V. PUBLIC HEALTH
Post-Traumatic Stress Disorder in Soldiers Deployed in Iraq and Afghanistan
VI. PSYCHOSOMATIC MEDICINE
Depressive Symptoms and Hostility Modulate Serum Interleukin-6 and C-Reactive Levels
VII. REGULATORY AFFAIRS
Dissemination of Information on Unapproved Uses of Medical Products
VIII. TARGET HEALTH

I. WHAT'S NEW?

Target Health Electronic Tool Box

Target Health has 4 web-based tools to facilitate the clinical trial process.

Target e*CRF® is our flagship product. There is no study too small and we will always beat the cost of a paper-based clinical trial. As studies get larger, we tend to drop data management costs by 50%.
Target Document® (TD) is fully released for commercial use. TD is our web-based document management and document sharing system. Very special prices for any of our readers. Our goal is to have high volume, high quality and low price.
Target Encoder® is fully integrated with Target e*CRF® and facilitates all coding of medical terminology.
Target Newsletter® allows the project manager to communicate to all study sites with data pulled from the database.

For more information, please contact Dr. Jules T. Mitchel or Joyce Hays. For new business opportunities, contact Dr. Jules T. Mitchel . Please visit our Website and Blog.

II. QUIZ (Fill In The Blanks)

Technique Transforms Millions of Points of Light into 3-D Images

Recent advances in fluorescence microscopy have enabled scientists to see inside cells with far better clarity than traditional optical imaging techniques, which are limited by the 1) ___ of light. In the February 8, 2008, issue of the journal Science, Xiaowei Zhuang and colleagues at Harvard University announced an advance that allows researchers to examine the complete three-dimensional 2) ___ of many of the tiniest structures of cells. The morphology indicates the status of the cells, both in terms of the health of the cells and in the case of primary isolates, the differentiation state. For those culturing embryonic stem cells the 3) ___ state is vital. The new technique is an expansion of a method the research team first developed, in 2006, to enable super-resolution imaging - 10 times better than what is attainable with conventional light 4) ___ - in two dimension. In 2006, Zhuang developed stochastic optical reconstruction microscopy (STORM), a super-resolution technique that uses fluorescing probes that can be turned on and off to let researchers zero in on some of the finest details of cellular 5) ___. Other methods of super-resolution imaging include photoactivated localization microscopy (PALM), developed in 2006; stimulated emission depletion (STED); and saturated structured illumination microscopy (SSIM). Zhuang says the instrumentation needed for 3D STORM is readily available. Chances are, any imaging center with a 6) ___ microscope setup can use it for this method with just little bit of modification. The data analysis needed to generate an image, however, is more complex. A complete STORM image is actually the compilation of millions of light points, representing the positions of the 7) ___ of interest, each of which must be precisely localized in three dimensions. The team is continually refining the complicated algorithms they developed for this data analysis, but hope to eventually develop user-friendly 8) ___ that will make 3D STORM readily accessible. The addition of the third dimension of super-resolution is one of a series of improvements to the original STORM technique. In 2007, this research group introduced new fluorescent labels that are compatible with STORM imaging, enabling researchers to track different types of proteins at the same time using multi-color imaging..

ANSWERS: 1) wavelength; 2) morphology; 3) differentiation; 4) microscopy; 5) structures; 6) fluorescence; 7) molecules; 8) software

III. HISTORY OF MEDICINE HONORS PRESIDENT'S DAY

Medical Life in Colonial Virginia – George Washington

Though basically a strong, healthy man, George Washington had been subject to the same ills that plagued most eighteenth-century Virginians. The kinds of health problems Washington encountered during his sixty-seven years and the way he dealt with them typify both the state of medicine and the kinds of care available at that time.. Born in 1732, George Washington survived the high-mortality years of early childhood when intestinal parasites, severe diarrheas, and respiratory problems such as scarlet fever, measles, and bacterial infections took so many young Virginians‘ lives. At age 17, he became victim to the bite of a plasmodium- infected mosquito. For the rest of his life, Washington suffered from periodic and sometimes severely debilitating bouts of malaria. He had one bout with smallpox in 1751, which left him immune to the disease but scarred for life. Gilbert Stuart chose not to depict the resultant deep pittings on Washington’s face in his famous portrait of the president painted in 1796. During his lifetime, Washington suffered at least ten attacks of serious illness, some disabling him for as long as a year. Between 1755 and 1768, he contracted dysentery at least three times, once for five weeks during the French and Indian War at Fort Duquesne. In 1789 and 1790, shortly after assuming the presidency, Washington was stricken twice with pneumonia. Washington’s false teeth have always excited interest among the public, perhaps because they survived him and are thus the only tangible remains of our nation’s first president. His first tooth extraction occurred in 1754 at age twenty-two, and his last, removing his last natural tooth, in 1796. Washington consulted several dentists over the years and replaced his dentures, in part or in full, at least nine times between 1781 and 1798. Washington did not have the aversion to or fear of physicians evinced by some other 18th-century Virginians. Yet, like most of his neighbors, he preferred to care for himself without outside medical assistance. To that end, he regularly ordered large quantities of common medicines and even some medicines from London. He also owned and presumably used some medical guides. Washington subscribed to the humoral theory of disease and, consistent with that thinking, he did not shy away from recommending bloodletting for his own or his “people’s” ailments when he thought it necessary. That same attitude toward bleeding later played a significant role in the president’s final illness. Despite a wariness of quacks, he did on occasion use itinerant quacks himself and even purchased a set of the popular Perkins’s Metallic Tractors in 1796. These implements were pairs of rods designed, when dragged over the affected part, to remove pains and inflammations from the body. Washington was already declining in health by 1798, but he remained active at Mount Vernon until two days before his death in December 1799.. The medical story behind his death describes the state of medicine and of approaches to sickness in the 18th century. On Thursday, 12 December, the former president was out riding. The weather, cloudy and cold in the morning, turned worse in the afternoon as rain, sleet, and snow fell alternately. Washington returned home at three, wet but unwilling to change until he had done a few more chores in the house and eaten. The next afternoon, after the snow had stopped, he went outside briefly to mark some trees for removal. Later that evening he complained of a cold and sore throat but told Tobias Lear, his personal secretary, “You know I never take anything for a cold. Let it go as it came.” At three the next morning, Washington awoke feeling sick and could breathe only with difficulty. He had his overseer come and bleed him and tried to swallow a mixture of molasses, vinegar, and butter that Lear gave him to relieve his throat. Washington choked on it and almost suffocated in a coughing fit. His old friend Dr. James Craik arrived later that morning, took more blood, and applied a blister to his throat. A vinegar gargle and steam inhalation did little to change the president’s condition, nor did another bleeding. Craik called in Dr. Gustavus Brown from nearby Port Tobacco, Maryland, and Elisha Dick, a young physician from Alexandria. They arrived between 3:30 and 4:00 p.m., removed more blood, gave the president a laxative and an emetic, and blistered him again. Doctor Dick wished to relieve Washington ’s breathing problem by opening his windpipe surgically using a procedure known as tracheotomy, something that had been done occasionally in the past but never on so illustrious a person as Washington. The two older physicians opposed the procedure, intimidated by the responsibility of caring for the former president and well aware of future public scrutiny of their actions. Dick opposed the excessive bleeding the other two physicians were using but was overruled again. Washington seemed resigned to his fate and even told Lear at one point, “My breath cannot last long. I believed from the first that the disorder would prove fatal.” He died quietly at about 11 p.m. that night. The president probably died of a severe streptococcal infection, aggravated by blood loss and dehydration.

IV. WOMEN'S HEALTH

Smoking and Risk of Preeclampsia

Preeclampsia is an illness arising only in pregnancy, which can affect the mother, her unborn child or, most commonly, both. It can develop at any time in the second half of pregnancy - even as late as several days after delivery. In the mother, the condition causes a number of symptomless disturbances - including raised blood pressure (hypertension) and leakage of protein into the urine (proteinuria) - which can progress to serious illness if undetected. The unborn baby may grow more slowly than normal or suffer potentially dangerous oxygen deficiency. A study published online in Hypertension (February 7, 2008) studied phenotypic and clinical outcome data in an observational, multicenter cohort study of 1001 Western European white women and their singleton babies, with stringently defined moderate-to-severe preeclampsia. Ninety women admitted to being current smokers and 71 had stopped smoking before entry to the study. Across the categories of never-smoker, stopped, and current smoker there were significant increases in the proportion of women delivering before 34 weeks’ gestation (P=0.011), delivering a baby below the third birth weight centile (P<0.001), or delivering a baby with any adverse outcome (P=0.011). By comparison with never-smokers, smoking during pregnancy was associated with a doubling of risk of being delivered before 34 weeks’ (odds ratio: 1.98; P=0.004), of delivering babies below the third centile of corrected birth weight (odds ratio: 2.20; P<0.0001), or for their babies to have any adverse outcome (odds ratio: 1.87; P<0.006). Worryingly, the risk of developing eclampsia was increased 5-fold (odds ratio: 4.88; P=0.005). The proportion of smokers in these preeclamptic women was lower than in the pregnant population generally. However, preeclampsia still carries significant perinatal morbidity, and cigarette smoking in preeclamptic pregnancies exacerbates this. Stopping smoking decreases the risks. According to the authors, smoking in young women should be a particular target for advice by their physician before pregnancy.

V. PUBLIC HEALTH

Post-Traumatic Stress Disorder in Soldiers Deployed in Iraq and Afghanistan

A prospective cohort analysis study published in the British Medical Journal (2008;336:366-371), was performed to describe new onset, and persistence of, self reported post-traumatic stress disorder symptoms in a large population based military cohort, many of whom were deployed in support of the wars in Iraq and Afghanistan. For the study, survey enrollment data was obtained from the millennium cohort (July 2001 to June 2003) before the wars in Iraq and Afghanistan. Follow-up (June 2004 to February 2006) data on health outcomes were collected from 50,184 participants. The main outcome measure was self reported post-traumatic stress disorder as measured by the posttraumatic stress disorder checklist - civilian version using Diagnostic and Statistical Manual of Mental Disorders, fourth edition criteria. More than 40% of the cohort were deployed between 2001 and 2006, and that between baseline and follow-up, 24% were deployed for the first time in support of the wars in Iraq and Afghanistan. New incidence rates of 10-13 cases of post-traumatic stress disorder per 1000 person years occurred in the millennium cohort. New onset self reported post-traumatic stress disorder symptoms or diagnosis were identified in 7.6-8.7% of deployers who reported combat exposures, 1.4-2.1% of deployers who did not report combat exposures, and 2.3-3.0% of non-deployers. Among those with self reported symptoms of post-traumatic stress disorder at baseline, deployment did not affect persistence of symptoms. It was concluded that after adjustment for baseline characteristics, these prospective data indicate a threefold increase in new onset self reported post-traumatic stress disorder symptoms or diagnosis among deployed military personnel who reported combat exposures. The findings define the importance of post-traumatic stress disorder in this population and emphasize that specific combat exposures, rather than deployment itself, significantly affect the onset of symptoms of post-traumatic stress disorder after deployment

VI. PSYCHOSOMATIC MEDICINE

Depressive Symptoms and Hostility Modulate Serum Interleukin-6 and C-Reactive Levels

Recent evidence suggests that depressive symptoms and hostility may act together, as interacting factors, to have an effect on the circulating levels of inflammatory markers relevant to coronary artery disease. As a result, a study published in Psychosomatic Medicine (2008;70:197-204), was performed to examine the cross-sectional associations of depressive symptoms, hostility, and their interaction with circulating levels of two such inflammatory markers - interleukin-6 (IL-6) and C-reactive protein (CRP). For the study, a total of 316 healthy, older adults underwent a blood draw for the assessment of serum IL-6 and CRP and completed the Beck Depression Inventory-II and the Cook-Medley Hostility Scale. Regression analyses were performed to examine depressive symptoms, hostility, and their interaction as predictors of serum IL-6 and CRP. Results showed that after adjustment for demographic factors, cardiovascular risk factors, and health behaviors, there was a significant interaction of depressive symptoms and hostility interactions for serum IL-6 (p < .01) and CRP (p < .05). Simple slope analyses revealed that hostility was positively related to serum IL-6 only among individuals with higher depressive symptoms. The pattern of results was similar for serum CRP, although none of the simple slopes was significant. According to the authors, the findings suggest that depressive symptoms may moderate the hostility-inflammation relationship such that hostility may augment inflammatory processes relevant to coronary artery disease only in the presence of depressive symptoms. The authors added that the results also extend previous findings from younger adults to older adults from the general community.

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.

Dissemination of Information on Unapproved Uses of Medical Products

The FDA has issued draft guidance on "Good Reprint Practices" for industry use in the distribution of medical or scientific journal articles and reference publications that involve unapproved uses of FDA-approved drugs and medical devices. According to FDA, research articles that discuss unapproved uses of FDA-approved drugs and devices can contribute to the practice of medicine and may even constitute a medically recognized standard of care. FDA added that the guidance also safeguards against off-label promotion. Previously, Section 401 of the Food and Drug Administration Modernization Act set out guidelines that allowed the dissemination of information on unapproved uses of FDA-approved products. As long as the guidelines were met by the manufacturers, the dissemination of such materials was not viewed by the FDA as evidence of an intent to promote the product for an "off-label" use. However, Section 401 expired on Sept. 30, 2006. The FDA's "Good Reprint Practices" draft guidance recommends principles manufacturers should follow when they distribute scientific or medical journal reprints, articles, or reference publications. Some of the principles include ensuring that the article or reference be published by an organization that has an editorial board. The organization also should fully disclose any conflicts of interest or biases for all authors, contributors or editors associated with the journal article. Articles should be peer-reviewed and published in accordance with specific procedures. In addition, the draft guidance recommends against distribution of special supplements or publications that have been funded by one or more of the manufacturers of the product in the article, and articles that are not supported by credible medical evidence are considered false and misleading and should not be distributed. The FDA still retains legal authority to determine whether distribution of an article or publication constitutes promotion of an unapproved "new use," or whether such activities cause a product to be considered misbranded or adulterated under The Federal Food, Drug and Cosmetic Act. The FDA welcomes public comments on the draft guidance. Typed comments should be submitted within 60 days of the Federal Register notice announcing the availability of the draft guidance.

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.

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Dr. Jules T. Mitchel, President
Ms Joyce Hays, CEO