Holiday Wishes 2011 and Happy New Year 2012



All of us at Target Health Inc. wish our 4,000-plus loyal readers of OnTARGET from all around the world, HOLIDAY GREETINGS and HAPPY NEW YEAR.


ON TARGET will take a vacation till after the New Year.


For more information about Target Health contact Warren Pearlson (212-681-2100 ext. 104). For additional information about software tools for paperless clinical trials, please also feel free to contact Dr. Jules T. Mitchel or Ms. Joyce Hays. The Target Health software tools are designed to partner with both CROs and Sponsors. Please visit the Target Health Website at

Two New Disinfection Techniques May Revolutionize Hospital Room Cleaning



A new technology known as HINS-light decontaminates the air and exposed surfaces by bathing them in a narrow spectrum of visible-light wavelengths. (Credit: Image courtesy of University of Strathclyde)




A pioneering lighting system that can kill hospital superbugs, including MRSA and C.1) ___, has been developed by researchers at the University of Strathclyde in Glasgow, Scotland. The technology decontaminates the air and exposed surfaces by bathing them in a narrow spectrum of visible-light wavelengths, known as HINS-light. Clinical trials at Glasgow Royal Infirmary have shown that the HINS-light Environmental Decontamination System provides significantly greater reductions of bacterial pathogens in the hospital environment than can be achieved by cleaning and disinfection alone, providing a huge step forward in hospitals’ ability to prevent the spread of 2) ___. According to the researchers, “The technology kills pathogens but is harmless to 3) ___ and staff, which means for the first time, hospitals can continuously disinfect wards and isolation rooms.


The system works by using a narrow spectrum of visible-light wavelengths to excite molecules contained within bacteria. This in turn produces highly reactive chemical species that are lethal to bacteria such as methicillin-resistant Staphylococcus aureus, or 4) ___, and Clostridium difficile, known as C.diff. The clinical trials have shown that the technology can help prevent the environmental transmission of pathogens and thereby increase patient safety.


The technology uses HINS-light which has a violet hue, but the research team has used a combination of LED technologies to produce a warm white lighting system that can be used alongside normal hospital lighting. Decontamination methods involving gas sterilants or UV-light can be hazardous to staff and patients, while cleaning, disinfection and hand washing, although essential routine procedures, have limited effectiveness and problems with compliance. HINS-light is a safe treatment that can be easily automated to provide continuous disinfection of wards and other areas of the clinical environment. The pervasive nature of 5) ___ permits the treatment of air and all visible surfaces, regardless of accessibility, either through direct or reflected exposure to HINS-light within the treated environment.


The technology was developed in Strathclyde’s pioneering Robertson Trust Laboratory for Electronic Sterilization Technologies (ROLEST), which is dedicated to controlling infection in today’s healthcare environments.


“This is the future, because many hospital 6) ___ are preventable with better cleaning methods,” says Dick Zoutman, who is also Quinte Health Care’s new Chief of Staff. “It has been reported that more than 100,000 people in North America die every year due to hospital acquired infections at a cost of $30 billion. That’s 100,000 people every year who are dying from largely preventable infections.” Dr. Zoutman has also used this disinfection technology to kill bed 7) ___. A major U.S. hotel chain has already expressed interest in the technology because of its potential to save the company millions of dollars in lost revenue and infected furniture.


Dr. Zoutman worked in collaboration with Dr. Michael Shannon of Medizone International at laboratories located in Innovation Park, Queen’s University. Medizone is commercializing the technology and the first deliveries are scheduled for the first quarter of 2012. The new technology involves pumping a Medizone-specific ozone and hydrogen 8) ___ vapor gas mixture into a room to completely sterilize everything – including floors, walls, drapes, mattresses, chairs and other surfaces. It is far more effective in killing bacteria than wiping down a room. Dr. Zoutman says the technique is similar to what we now know Mother Nature uses to kill 9) ___ in humans. When an antibody attacks a germ, it generates ozone and a minute amount of hydrogen peroxide producing a new highly reactive compound that is profoundly lethal against bacteria, viruses and mold.


“It works well for Mother Nature and is working very well for us,” says Dr. Zoutman.


There are other disinfecting technologies that involve pumping gas into a room, but Medizone’s method is the only one that sterilizes as well as surgical instrument cleaning. It also leaves a pleasant smell and doesn’t affect any medical equipment in the room. The entire disinfection process is also faster than other methods — it takes less than one hour. Dr. Zoutman says the technology could also be used in food preparation areas and processing plants after outbreaks such as listeria and to 10) ___ cruise ships after an infection outbreak.  Study results on the process are published in the December issue of the American Journal of Infection Control.


ANSWERS: 1) difficile; 2) infection; 3) patients; 4) MRSA; 5) light; 6) deaths; 7) bugs; 8) peroxide; 9) bacteria; 10) disinfect

Scientists Solve Puzzle of Black Death’s DNA


A draft sequence of the Yersinia pestis genome has been
reconstructed using DNA extracted from victims of the Black
Death. Source: Museum of London



Advancing science: the remains of plague victims in a 14th-century London cemetery. Source: Museum of London



After the Black Death reached London in 1348, about 2,400 people were buried in East Smithfield, near the Tower of London, in a cemetery that had been prepared for the plague’s arrival. From the teeth of four of those victims, researchers have now reconstructed the full DNA of a microbe that within five years decimated one-third to one-half of the population of Western Europe. The bacterium that causes plague, Yersinia pestis, is still highly virulent today but has different symptoms, leading some historians to doubt that it was the agent of the Black Death.


Those doubts were laid to rest last year by analysis of the bacterium’s DNA in plague victims from mass graves across Europe. With the full genome now in hand, the researchers hope to recreate the microbe itself so as to understand what made the Black Death outbreak so deadly. So far, the evidence points more toward the conditions of the time than to properties of the bacterium itself. The genome recovered from the East Smithfield victims is remarkably similar to that of the present-day bacterium, says the research team, led by Kirsten I. Bos of McMaster University in Ontario and Johannes Krause of the University of Tubingen in Germany.


This is the first time the genome of an ancient pathogen has been reconstructed, opening the way to tracking other ancient epidemics and how their microbes adapted to human hosts. The bacterium’s genome consists of a single chromosome, about 4.6 million DNA units long, and three small rings of DNA called plasmids. In the 660 years since the Black Death struck, only 97 of these December 2012). Dr. Krause and others reported the DNA sequence of one of the plasmids in August. The changes in the genome will be studied one by one to see how each affects the microbe’s virulence. The researchers hope eventually to modify a living plague bacterium so that its genome is identical to that of the agent of the Black Death. Such a microbe could be handled only in special secure facilities.


If the microbe’s genome is so little changed, the deadliness of the Black Death may reflect the condition of its medieval victims. The climate was cooling, heavy rains rotted out crops and caused frequent famines, and the Hundred Years’ War began in 1337. People were probably already suffering from malnutrition and other diseases when the plague arrived like the fourth horseman of the apocalypse.


Recovery of the medieval plague bacterium’s full genome is a technical tour de force. The DNA had been degraded into millions of small fragments that were overwhelmed in number by DNA from the human host and from the bacteria that consumed the body after death. Dr. Krause’s team fished out the plague DNA by using DNA from the modern bacterium, relying on the fact that DNA strands bind to DNA of complementary sequence. “This is a major technological step forward, a great advance for the entire field of DNA and pathogens,“ said Mark Achtman, an expert on ancient plague at University College Cork in Ireland. But Dr. Achtman disagreed with one issue in Dr. Krause’s findings, that of whether Yersinia pestis also caused the outbreak in the sixth century known as the Justinian plague. When the full genome of the medieval bacterium is compared with DNA recovered from other known human outbreaks, a tree of descent can be constructed. The Black Death genome lies so close to the root of the tree that the human pathogen probably did not exist much earlier or, if it did, has vanished without any descendants, Dr. Krause’s team says. This implies that the Justinian plague was caused by some other agent. Dr. Achtman said this conclusion was incorrect because the Krause team had omitted DNA from several human cases that place the root of the tree much further back in time. Dr. Krause said he had left these cases out because they seemed unreliable.


The modern plague bacterium changes its DNA units slowly, but it does quite often rearrange the order of its genes. Some experts believe gene order can affect pathogenicity. Dr. Krause had available only tiny fragments of DNA, so although he was able to reconstruct all the medieval bacterium’s genes he could not establish the exact order in which the genes were arranged, leaving open the possibility that the bacterium was inherently more pathogenic because its genome was differently organized. Paul Keim, an expert on infectious bacteria at Northern Arizona University, said that work by Dr. Achtman and Dr. Krause had shown that the Black Death “was really a series of epidemics coming out of China and sweeping across the susceptible ecological situation“ created by the culture of medieval Europe. The plague in each outbreak probably did not persist very long and was repeatedly re-established by new infections from East Asia, where the bacterium is still endemic in small rodents like marmots. “We don’t have a human ecological situation comparable today, plus it is really easy to break the transmission cycle with antibiotics and public health,“ Dr. Keim said. There are still small outbreaks, like one in Madagascar in the 1990s, but “a multiyear large human outbreak is inconceivable in this day,“ he said.


Besides the Justinian plague and the Black Death, a third great wave of plague swept out of China in 1894, causing an epidemic in San Francisco in 1900 and killing millions of people in India.


All the teeth used in the study will be returned to the skulls from which they were taken, now in a London museum whose archaeologists excavated the East Smithfield cemetery in the 1980s. Source: NYTimes, Fall 2011, by Nicholas Wade


Gene Therapy Helps Patients with Hemophilia B



Hemophilia B is less common than hemophilia A, a deficiency of clotting factor VIII. About 1 in 5 hemophilia patients has hemophilia B, while the other four have hemophilia A. Hemophilia is an inherited condition that affects men more frequently. Worldwide, about 1 in 5,000 men are born with hemophilia A and 1 in 25,000 men are born with hemophilia B each year. People with hemophilia bleed more following trauma than people without the disease, and those with severe disease may bleed spontaneously. Hemophilia B patients are unable to produce enough human clotting factor IX, also referred to as FIX, which is essential for normal blood clotting. Liver cells are the only cells in the body capable of producing a form of factor IX that is active in the clotting process.


According to an article published online in the New England Journal of Medicine (10 December 2011), an experimental gene therapy technique has been shown to boost the production of a vital blood clotting factor in six people with hemophilia B. As a result the therapy could give patients a long-term solution for preventing prolonged bleeding episodes and spontaneous bleeding.


“Hemophilia has long been one of the disorders thought most likely to be correctible with gene therapy, but previous approaches to deliver the gene have been disappointing. Results from this study represent a promising step toward making gene therapy a viable treatment option for hemophilia B,” said Susan B. Shurin, M.D., acting director of the NIH’s National Heart, Lung, and Blood Institute (NHLBI),. “If future studies support these findings, it would bring a significant improvement in the quality of life for those living with the disease.”


In preparation for the clinical trial, the FIX gene was packaged in a modified adeno-associated virus, AAV8, which targets liver cells. This potentially allowed the normal FIX gene to be delivered using intravenous infusion to the liver cells which should allow the patients to produce more FIX. The clinical trial then evaluated six people with severe hemophilia B who were producing clotting factor IX at less than 1% of normal levels before receiving the gene therapy. Prior to enrolling in the study, participants were receiving the standard treatment for severe hemophilia B of infusions of manufactured FIX several times a month.


Results showed that after receiving the FIX gene therapy, each study subject produced FIX at between 2 and 11% of normal levels. In the short-term follow-up period (six to 16 months), four of the six participants no longer required FIX infusions for routine bleeding. The other two participants required FIX infusions less frequently than before the study.


According to the authors, the unique feature of this approach is the use of AAV8 to deliver the gene to the appropriate cells, and if future studies show that immunologic or other factors do not limit its long-term effectiveness, people with hemophilia B could produce their own FIX and potentially avoid reliance upon FIX infusions. While more work is needed, these results are more promising than prior attempts at gene therapy for the hemophilias.

People with a Form of Muscular Dystrophy May Have Elevated Cancer Risk


Myotonic muscular dystrophy (MMD) is part of a group of inherited disorders and the most common form of muscular dystrophy in adults. There are two main types of MMD, type 1 and type 2, which are caused by mutations in two different genes. In both cases, the mutation is a result of greater than normal repetition of part of the gene along a segment of DNA. Repetition of parts of genes is common but, in these cases, the repeat length is so excessive that it disrupts normal gene function. Doctors who treat MMD patients occasionally observe the development of benign and malignant tumors. However, it has not been clear whether these cancers were part of the myotonic dystrophy syndrome or just a coincidence.


According to a study published online in the Journal of the American Medical Association (14 December 2100), adults with MMD may be at increased risk of developing cancer. The authors suggest that some of the genetic changes that lead to MMD may also be responsible for the observed increase in cancer risk, but more research is needed to confirm this hypothesis.


To determine if MMD patients were at higher risk of cancer than the general population, the authors identified 1,658 Scandinavian patients with MMD who were reported to the Swedish Inpatient Hospital Discharge Register from 1987 through 2004 or the Danish National Patient Discharge Registry between 1977 and 2008. The researchers then linked the patients to the corresponding cancer registry in Sweden and Denmark.


In the study, the investigators describe risks of all cancers combined and by cancer type. In addition, they analyzed risks according to age and gender. Results showed that the cancer risk of MMD patients was twice that of the general population, with the majority of the excess explained by cancers of the colon, brain, endometrium, and ovaries. The excess risk was similar in both the Swedish and Danish cohorts. The study also found that, after cancers of the genital organs were excluded, both females and males with MMD had the same excess risk of developing cancer.


A limitation of this work, according to the authors, was that they did not have information about known cancer risk factors, such as smoking. They also lacked information on which MMD type each patient had, so they were unable to determine if the increased cancer risk they observed in those with MMD was common to both or confined to a specific type.

Study Shows Additional Benefits of Progesterone in Reducing Preterm Birth Risk



Pregnant women with a short cervix are at risk of pre-term birth and at an increased risk of delivering early. The cervix is the part of the uterus that shortens and opens during labor for the infant to pass through. Preterm infants, born three weeks or more before a full 40-week term, are at increased risk for death in the first year of life, as well as for breathing difficulties, cerebral palsy, learning disabilities, blindness and deafness. A previous NIH study had earlier indicated that progesterone, a naturally occurring hormone, was effective in reducing the preterm birth rate.


According to a study published online in the American Journal of Obstetrics and Gynecology (12 December 2011), an analysis of five previous studies has uncovered additional evidence of the effectiveness of progesterone in reducing the rate of preterm birth among a high-risk category of women.


The current study is a meta-analysis, which is a statistical technique that combines the data from several studies addressing a related research question. By combining information from the five studies, results from treatment of 775 women became available. By comparing women who received progesterone treatment with those who did not, the authors separately calculated the rate of preterm delivery at each week of gestation.


Results showed that progesterone treatment in doses ranging from 90 milligrams to 200 milligrams per day tested in the previous studies substantially reduced the risk of delivery in the 27th to 34th weeks of gestation. For example, progesterone reduced preterm delivery before week 28 by half. The study also concluded that even when the mother delivers before full term, progesterone treatment can reduce the likelihood that the infant will die (43%), have respiratory distress syndrome (52%), weigh less than 3.5 pounds (45%), be admitted for intensive care (25%), or require mechanical ventilation (34%).


Based on their findings, the authors recommended that pregnant patients be screened with ultrasound of the cervix routinely at 19 to 24 weeks of gestation. If a short cervix (10 to 20 millimeters) is detected, the authors recommended treatment with 90 mg per day of progesterone between weeks 20 and 37.

TARGET HEALTH excels in Regulatory Affairs. Each week we highlight new information in this challenging area.



FDA Approves Mechanical Cardiac Assist Device for Children with Heart Failure



Heart failure in children is much less common than in adults. Heart transplantation offers effective relief from symptoms. However, far fewer pediatric sized donor hearts are available for transplantation than for adults, limiting the use of heart transplantation in children and prolonging the waiting period until transplant can occur. In infants, the median waiting time for a donor heart is 119 days. Overall a reported 12-17% of children and 23% of infants die while on the wait list for a heart transplant.


The FDA has approved a medical device that supports the weakened heart of children with heart failure to help keep them alive until a donor for a heart transplant can be found. The mechanical pulsatile cardiac assist device is called the EXCOR Pediatric System, made by a German company, Berlin Heart. The device comes in graduated sizes to fit children from newborns to teens. The device consists of one or two external pneumatic (driven by air) blood pumps, multiple tubes to connect the blood pumps to heart chambers and the great arteries, and the driving unit.


In the primary U.S. study group of 48 patients, the use of the device was found to improve survival to transplant in patients when compared with the use of extracorporeal membrane oxygenation (ECMO) which is the current standard of care, although not FDA approved. Stroke, which can cause serious brain deficits, is a risk of the EXCOR Pediatric System.


The EXCOR was designated as a Humanitarian Use Device (HUD) by the Office of Orphan Products Development at the FDA. This designation is for medical devices intended to benefit patients in the treatment or diagnosis of a disease or condition that affects fewer than 4,000 individuals in the United States annually. The device was approved under a Humanitarian Device Exemption (HDE), a type of marketing application that is similar to a premarket approval application in that the level of safety required for approval is the same. Rather than having to show a reasonable assurance of effectiveness, devices submitted under the HDE marketing route need to prove that the probable benefit from use of the device outweighs the probable risk of illness or injury from its use to obtain the FDA’s approval. The FDA approval of an HDE authorizes an applicant to market the device subject to certain use restrictions. After the passing of the Pediatric Medical Device Safety and Improvement Act of 2007, HUDs intended and labeled for use in a pediatric population are permitted to be marketed for profit.


The FDA’s Orphan Products Grant Program supported the U.S. clinical trials for the EXCOR Pediatric System with grants of $400,000 per year for three years. For more information: Designating Humanitarian Use Devices

Lack of Alignment



By Mark L. Horn, MD, MPH, Chief Medical Officer, Target Health Inc.


A creative and provocative paper (Allan Detsky, What Patients Really Want From Health Care, JAMA: 14 December 2011) published just this week ought to give policymakers pause (or at the very least some food-for-thought).


The author confronts, in an unusually straightforward, and what will likely seem to some a “politically incorrect“ manner, a serious dilemma for health care policy makers. The piece identifies a significant disconnect between what patients actually want from the health care system and the goals of policymakers who, however well intended, may be engaged in designing a system with, from patients’ perspectives at least, misplaced priorities. Along the way some key shibboleths of conventional wisdom are seriously challenged (always fun). If the author is correct, health care policymakers across the political and philosophical spectrums are potentially seriously at odds with the public. The implications of this disconnect are both numerous and potentially serious.


Patients, when ill, evidently want rapid and easy access to a caring physician able to quickly initiate effective interventions with (no surprise here) minimal out of pocket costs; they are much less concerned about interacting with the system regularly to stay healthy or with a broad redesign of the system to focus on prevention. While these concerns are of special concern to the author, they are apparently not a major problem for patients. Finally, regarding economics, for insured patients the cost of their individual (covered) care is not an issue, nor is the overall rising cost of care for the nation of great concern. Patients want easy and rapid access to top of the line medicine when they’re sick and are willing to accept that this requires a progressively larger commitment of societal resources.


Although this is a somewhat unusual paper where the takeaways will likely vary with individuals’ political, economic, and social philosophies, there are some ?generic’ lessons as well.


Without venturing into the obviously dicey areas, it seems safe to conclude that these dichotomies in objectives between the public and policymakers imply either that system reform will receive suboptimal pubic enthusiasm or that meaningful market research, educational, and communication efforts will be required to understand what the public wants, help them understand whether their desires are realistic, and engage them more productively in rational system redesign.


This is necessarily a tall-order; however, even the possibility that after all the rancorous discussions and debates, the consequent policy changes, system interventions, and enormous resource allocations this disconnect with the pubic exists (e.g. the possibility that the paper is correct) suggests a potentially serious flaw in our processes.


We need to confirm the accuracy of this diagnosis quickly and prescribe the proper therapy.


However, in addressing preventative medicine, in addition to any conflicts with the health habits and behavior of our citizens, it must be said that there are other huge health risks beyond the control of our citizens such as air and water pollution, food deserts and how we are seduced by the junk food revolution.

Target Health ( a full service e*CRO, is committed to serve the pharmaceutical community through knowledge, experience, technology and connectivity. Target Health strives to optimize the life cycle of drugs, biologics and devices with expertise, leadership, innovation and teamwork. Target Health Inc. has fulltime staff dedicated to all aspects of Regulatory Affairs, Clinical Research, Biostatistics, Data Management, Strategic Planning and Drug and Device Development. Target Health is committed to the paperless clinical trial and has developed a full suite of eClinical Trial software including:

1) Target e*CRF® (EDC Made Simple)

2) Target e*CTMS™

3) Target Document®

4) Target Encoder®

5) Target e*Pharmacovigilance™

6) Target e*Monitoring™

7) Target Newsletter®

8) Target e*CTR™ (eSource, electronic medical record for clinical trials).

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.


261 Madison Avenue
24th Floor
New York, NY 10016
Phone: (212) 681-2100; Fax (212) 681-2105
Ms Joyce Hays, CEO
Dr. Jules T. Mitchel, President

©2011 Target Health Inc. All rights reserved