Target Health Attending and Exhibiting at ClinTech 2013


Target Health will be attending & exhibiting at ClinTech 2013, being held this year at the Loews Hotel In Philadelphia (March 11-13, 2013). At ClinTech 2013, you can learn more about the latest applications and operational strategies to meet the clinical demands of today. In addition, you should gain insight on how to achieve platform and technology integration for the future. Dr. Jules Mitchel, Target’s President and Warren Pearlson, Director Business Development will be attending. If you are planning to attend, please stop by and say hello.


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

How the Heart Works


The heart is an amazing organ. It continuously pumps oxygen and nutrient-rich 1) ___ throughout the body to sustain life. This fist-sized powerhouse beats (expands and contracts) 100,000 times per day, pumping five or six quarts of blood each minute, or about 2,000 gallons per day. As the heart 2) ___, it pumps blood through a system of blood vessels, called the circulatory system. The vessels are elastic, muscular tubes that carry blood to every part of the body.


Blood is essential. In addition to carrying fresh 3) ___ from the lungs and nutrients to the body’s tissues, it also takes the body’s waste products, including carbon dioxide, away from the tissues. This is necessary to sustain life and promote the health of all parts of the body.

There are three main types of blood 4) ___:


1. Arteries. They begin with the aorta, the large artery leaving the heart. Arteries carry oxygen-rich blood away from the heart to all of the body’s tissues. They branch several times, becoming smaller and smaller as they carry blood further from the heart and into organs.


2. Capillaries. These are small, thin blood vessels that connect the arteries and the veins. Their thin walls allow oxygen, nutrients, carbon dioxide, and other waste products to pass to and from our organ’s cells.


3. Veins. These are blood vessels that take blood back to the heart; this blood has lower oxygen content and is rich in waste products that are to be excreted or removed from the body. Veins become larger and larger as they get 5) ___ to the heart. The superior vena cava is the large vein that brings blood from the head and arms to the heart, and the inferior vena cava brings blood from the abdomen and legs into the heart.


This vast system of blood vessels — arteries, veins, and capillaries — is over 60,000 miles long. That’s long enough to go around the world more than twice. Blood flows continuously through your body’s blood vessels. Your heart is the 6) ___ that makes it all possible. The heart is located under the rib cage, slightly to the left of your breastbone (sternum) and between your lungs.


Looking at the outside of the heart, you can see that the heart is made of 7) ___. The strong muscular walls contract (squeeze), pumping blood to the rest of the body. On the surface of the heart, there are coronary arteries, which supply oxygen-rich blood to the heart muscle itself. The major blood vessels that enter the heart are the superior vena cava, the inferior vena cava, and the pulmonary veins. The pulmonary artery and the aorta exit the heart and carry oxygen-rich blood to the rest of the body.


On the inside, the heart is a four-chambered, hollow organ. It is divided into the left and right side by a muscular wall called the septum. The right and left sides of the heart are further divided into two top chambers called the atria, which receive blood from the veins, and two bottom chambers called ventricles, which pump blood into the arteries.


The atria and ventricles work together, contracting and relaxing to pump blood out of the heart. As blood leaves each chamber of the heart, it passes through a 8) ___. There are four heart valves within the heart:


1. Mitral valve

2. Tricuspid valve

3. Aortic valve

4. Pulmonic valve


The tricuspid and mitral valves lie between the atria and ventricles. The aortic and pulmonic valves lie between the ventricles and the major blood vessels leaving the heart. The heart valves work the same way as one-way valves in the plumbing of your home. They prevent blood from flowing in the wrong 9) ___. Each valve has a set of flaps, called leaflets or cusps. The mitral valve has two leaflets; the others have three. The leaflets are attached to and supported by a ring of tough, fibrous tissue called the annulus. The annulus helps to maintain the proper shape of the valve. The leaflets of the mitral and tricuspid valves are also supported by tough, fibrous strings called chordae tendineae. These are similar to the strings supporting a parachute. They extend from the valve leaflets to small muscles, called papillary muscles, which are part of the inside walls of the ventricles.


Blood flows through the heart with the right and left sides of the heart working together. Specific patterns are repeated over and over, causing blood to flow continuously to the heart, lungs, and body.


On the right side of the heart:


  • Blood enters the heart through two large veins, the inferior and superior vena cava, emptying oxygen-poor blood from the body into the right atrium of the heart.
  • As the atrium contracts, blood flows from your right atrium into your right ventricle through the open tricuspid valve.
  • When the ventricle is full, the tricuspid valve shuts. This prevents blood from flowing backward into the atria while the ventricle contracts.
  • As the ventricle contracts, blood leaves the heart through the pulmonic valve, into the pulmonary artery and to the lungs where it is oxygenated.


On the left side of the heart:


  • The pulmonary vein empties oxygen-rich blood from the lungs into the left atrium of the heart.
  • As the atrium contracts, blood flows from your left atrium into your left ventricle through the open mitral valve.
  • When the ventricle is full, the mitral valve shuts. This prevents blood from flowing backward into the atrium while the ventricle contracts.
  • As the ventricle contracts, blood leaves the heart through the aortic valve, into the aorta and to the body.


Once blood travels through the pulmonic valve, it enters your lungs. This is called the pulmonary circulation. From your pulmonic valve, blood travels to the pulmonary artery to tiny capillary vessels in the 10) ___. Here, oxygen travels from the tiny air sacs in the lungs, through the walls of the capillaries, into the blood. At the same time, carbon dioxide, a waste product of metabolism, passes from the blood into the air sacs. Carbon dioxide leaves the body when you exhale. Once the blood is purified and oxygenated, it travels back to the left atrium through the pulmonary veins.


Coronary Arteries of the Heart


Like all organs, your heart is made of tissue that requires a supply of oxygen and nutrients. Although its chambers are full of blood, the heart receives no nourishment from this blood. The heart receives its own supply of blood from a network of arteries, called the 11) __ arteries. Two major coronary arteries branch off from the aorta near the point where the aorta and the left ventricle meet:


  • Right coronary artery supplies the right atrium and right ventricle with blood. It branches into the posterior descending artery, which supplies the bottom portion of the left ventricle and back of the septum with blood.
  • Left main coronary artery branches into the circumflex artery and the left anterior descending artery. The circumflex artery supplies blood to the left atrium, side and back of the left ventricle, and the left anterior descending artery supplies the front and bottom of the left ventricle and the front of the septum with blood.


These arteries and their branches supply all parts of the heart muscle with blood. Coronary artery disease occurs when 12) ___ builds up in the coronary arteries and prevents the heart from getting the enriched blood it needs. If this happens, a network of tiny blood vessels in the heart that aren’t usually open called collateral vessels may enlarge and become active. This allows blood to flow around the blocked artery to the heart muscle, protecting the heart tissue from injury.


The heart beats when the atria and ventricles work together, alternately contracting and relaxing to pump blood through your heart. The electrical system of the heart is the power source that makes this possible. Your heartbeat is triggered by 13) ___ impulses that travel down a special pathway through the heart.


  • The impulse starts in a small bundle of specialized cells called the SA node (sinoatrial node), located in the right atrium. This node is known as the heart’s natural pacemaker. The electrical activity spreads through the walls of the atria and causes them to contract.
  • A cluster of cells in the center of the heart between the atria and ventricles, the AV node (atrioventricular node) is like a gate that slows the electrical signal before it enters the ventricles. This delay gives the atria time to contract before the ventricles do.
  • The His-Purkinje network is a pathway of fibers that sends the impulse to the muscular walls of the ventricles, causing them to 14) ___.


At rest, a normal heart beats around 50 to 99 times a minute. Exercise, emotions, fever, and some medications can cause your heart to beat faster, sometimes to well over 100 beats per minute.


ANSWERS: 1) blood; 2) beats; 3) oxygen; 4) vessels; 5) closer; 6) pump; 7) muscle; 8) valve; 9) direction; 10) lungs; 11) coronary; 12) plaque; 13) electrical; 14) contract

Circulatory Systems


Circulatory system: Historical artwork of a human figure with internal organs and blood vessels shown. This manuscript is part of the collection gathered by the English antiquary Elias Ashmole (1617-1692) and held at the Bodleian Library, Oxford, UK.



Living in the year 1535, what would you do if you didn’t feel well? You’ve had some problems with fatigue, feeling a little more tired than usual when you walked to the market and back. You tell this to your physician, and he sends you to another physician down the street, telling you there may be some problem with your circulation. When you get to the new physician, he tells you to take off your shirt and lie down on the bench. After a quick look in your mouth, he says your vital blood is probably alright. But he’s concerned that maybe your nutritive blood is not being made fast enough. Then he starts to feel around on your abdomen. He mentions that your liver is slightly enlarged and suggests that maybe you have not been eating well enough.


Confusion over the nature of the heart, the blood, and the role of the blood in the body had existed for centuries. Pliny the Elder, a Roman writer who lived from AD 23-79, and author of a 37-volume treatise entitled Natural History, wrote “The arteries have no sensation, for they even are without blood, nor do they all contain the breath of life; and when they are cut only the part of the body concerned is paralyzed – the veins spread underneath the whole skin, finally ending in very thin threads, and they narrow down into such an extremely minute size that the blood cannot pass through them nor can anything else but the moisture passing out from the blood in innumerable small drops which is called sweat.”


A century later Galen, a Greek physician who lived in the second century AD., spent his lifetime in observation of the human body and its functioning. Galen believed and taught his students that there were two distinct types of blood. ‘Nutritive blood’ was thought to be made by the liver and carried through veins to the organs, where it was consumed. ‘Vital blood’ was thought to be made by the heart and pumped through arteries to carry the “vital spirits.” Galen believed that the heart acted not to pump blood, but to suck it in from the veins. Galen also believed that blood flowed through the septum of the heart from one ventricle to the other through a system of tiny pores. He did not know that the blood left each ventricle through arteries.


Physicians, as well as citizens, of many cultures had their own beliefs concerning the nature of the heart and circulatory system. While the Greeks believed that the heart was the seat of the spirit, the Egyptians believed the heart was the center of the emotions and the intellect. The Chinese believed the heart was the center for happiness. Even our modern society continues to put emotions under the control of the heart, speaking of having a broken heart when a loved one leaves, or stealing one’s heart around Valentine’s Day. These beliefs continued to be taught and taken as law until an English physician named William Harvey challenged them in the late 1620’s.


William Harvey was born in 1578 in Folkstone, England. The eldest of seven sons, Harvey received a Bachelor of Arts degree from Cambridge in 1597. He then studied medicine at the University of Padua, receiving his doctorate in 1602. By all measures, Harvey was successful. After he finished his studies at Padua, he returned to England and set up practice. He then married Elizabeth Brown, daughter of the court physician to Queen Elizabeth I and King James I. This put in him in position to be noticed by the aristocracy, and Harvey quickly moved up the ladder. Eventually, he became court physician to both King James I and King Charles I. While acting as court physician, Harvey was able to conduct his research in human biology and physiology. Harvey focused much of his research on the mechanics of blood flow in the human body. Most physicians of the time felt that the lungs were responsible for moving the blood around throughout the body. Harvey questioned these beliefs and his questions directed his life-long scientific investigations.


Opened heart showing anatomy and blood flow (Carolina Biological Supply)



Harvey’s experiments involved both direct dissection and physiological experiments on animals. His observations of dissected hearts showed that the valves in the heart allowed blood to flow in only one direction. Direct observation of the heartbeat of living animals showed that the ventricles contracted together, dispelling Galen’s theory that blood was forced from one ventricle to the other. Dissection of the septum of the heart showed that it contained arteries and veins, not perforations. When Harvey removed the beating heart from a living animal, it continued to beat, thus acting as a pump, not a sucking organ. Harvey also used mathematical data to prove that the blood was not being consumed. Removal of the blood from human cadavers showed that the heart could hold roughly two ounces of blood. By calculating the number of heartbeats in a day and multiplying this by two ounces, he showed that the amount of blood pump far exceeded the amount that the body could possibly make. He based this figure on how much food and liquids a person could consume. To Harvey, this showed that the teaching by Galen that the blood was being consumed by the organs of the body was false. Blood had to be flowing through a ‘closed circuit’ instead. Even though he lacked a microscope, Harvey theorized that the arteries and veins were connected to each other by capillaries, which would later be discovered by Marcello Malpighi some years after Harvey’s death.


Harvey did not let the beliefs of Galen concerning the role of natural, vital, and animal spirits and their effects on physiology affect his objectivity. Instead, Harvey asked simple, pointed questions, the types of questions that even today are the hallmark of good scientific research. Harvey asked such questions as why did both the lungs and the heart move if only the lungs were responsible for causing circulation of blood? Why should, as Galen suggested, structurally similar parts of the heart have very different functions? Why did ‘nutritive’ blood appear so similar to ‘vital’ blood? These, and other, questions gave Harvey his focus.


Harvey’s lecture notes show that he believed in the role of the heart in circulation of blood through a closed system as early as 1615. Yet he waited 13 years, until 1628, to publish his findings in his work Exercitatio anatomica de motu cordis et sanguinis in animalibus or On the Movement of the Heart and Blood in Animals. Why did he wait so long? Galenism, or the study and practice of medicine as originally taught by Galen, was almost sacred at the time Harvey lived. No one dared to challenge the teachings of Galen. Like most physicians of his day, William Harvey, was trained in the ways of Galen. Conformation was not only the norm, but was also the key to success. To rebel against the teachings of Galen could quickly end the career of any physician. Perhaps this is why he waited.


Harvey’s hesitation proved well-founded. After his work was published, many physicians and scientists rejected him and his findings. Using different assumptions of the amount of blood contained in the heart, scientists argued that the blood could indeed be consumed. Controversy raged for a full twenty years after publication of “On the Movement of the Heart and Blood in Animals.” Yet, with time, more and more physicians and researchers accepted Harvey’s hypotheses. Harvey’s work raised questions. If blood was not consumed by organs, how did different parts of the body obtain nourishment? If the liver did not make blood from food, where did blood originate? Medical practice in Harvey’s time, however, changed little. Even though the mechanics of blood flow were beginning to be accepted, the causes of many diseases were still thought to be involved with mysterious spirits. In fact, the practices of bleeding, lancing, and leeching increased in the years following Harvey’s work. However, medicine did make some advances, for it was during the seventeenth century that administering medicine through intravenous injections came into practice.


William Harvey’s classic work became the foundation for all modern research on the heart and cardiovascular medicine. It has been said that Harvey’s proof “of the continuous circulation of the blood within a contained system was the seventeenth century’s most significant achievement in physiology and medicine.” Further, his work is considered to be one of the most important contributions in the history of medicine. Without the understanding of the circulatory system made possible by Harvey’s pioneering work, the medical miracles that we think are commonplace would be impossible.


The Types of Circulatory Systems


Circulation of the blood serves to move blood to a site or sites where it can be oxygenated, and where wastes can be disposed. Circulation then serves to bring newly oxygenated blood to the tissues of the body. As oxygen and other chemicals diffuse out of the blood cells and into the fluid surrounding the cells of the body’s tissues, waste produces diffuse into the blood cells to be carried away. Blood circulates through organs such as the liver and kidneys where wastes are removed, and back to the lungs for a fresh dose of oxygen. And then the process repeats itself. This process of circulation is necessary for continued life of the cells, tissues and even of the whole organisms. Before we talk about the heart, we should give a brief background of the two broad types of circulation found in animals. We will also discuss the progressive complexity of the heart as one moves up the evolutionary ladder.


Many invertebrates do not have a circulatory system at all. Their cells are close enough to their environment for oxygen, other gases, nutrients, and waste products to simply diffuse out of and into their cells. In animals with multiple layers of cells, especially land animals, this will not work, as their cells are too far from the external environment for simple osmosis and diffusion to function quickly enough in exchanging cellular wastes and needed material with the environment.


In higher animals, there are two primary types of circulatory systems — open and closed. Arthropods and most mollusks have an open circulatory system. In this type of system, there is neither a true heart or capillaries as are found in humans. Instead of a heart there are blood vessels that act as pumps to force the blood along. Instead of capillaries, blood vessels join directly with open sinuses. “Blood,” actually a combination of blood and interstitial fluid called ‘hemolymph’, is forced from the blood vessels into large sinuses, where it actually baths the internal organs. Other vessels receive blood forced from these sinuses and conduct it back to the pumping vessels. It helps to imagine a bucket with two hoses coming out of it, these hoses connected to a squeeze bulb. As the bulb is squeezed, it forces the water along to the bucket. One hose will be shooting water into the bucket, the other is sucking water out of the bucket. Needless to say, this is a very inefficient system. Insects can get by with this type system because they have numerous openings in their bodies (spiracles) that allow the “blood” to come into contact with air.


The closed circulatory system of some mollusks and all higher invertebrates and the vertebrates is a much more efficient system. Here blood is pumped through a closed system of arteries, veins, and capillaries. Capillaries surround the organs, making sure that all cells have an equal opportunity for nourishment and removal of their waste products. However, even closed circulatory systems differ as we move further up the evolutionary tree. One of the simplest types of closed circulatory systems is found in annelids such as the earthworm. Earthworms have two main blood vessels — a dorsal and a ventral vessel –which carry blood towards the head or the tail, respectively. Blood is moved along the dorsal vessel by waves of contraction in the wall of the vessel. These contractible waves are called ‘peristalsis.’ In the anterior region of the worm, there are five pairs of vessels, which we loosely term “hearts,” that connect the dorsal and the ventral vessels. These connecting vessels function as rudimentary hearts and force the blood into the ventral vessel. Since the outer covering (the epidermis) of the earthworm is so thin and is constantly moist, there is ample opportunity for exchange of gases, making this relatively inefficient system possible. There are also special organs in the earthworm for the removal of nitrogenous wastes. Still, blood can flow backward and the system is only slightly more efficient than the open system of insects.


As we come to the vertebrates, we begin to find real efficiencies with the closed system. Fish possess one of the simplest types of true heart. A fish’s heart is a two-chambered organ composed of one atrium and one ventricle. The heart has muscular walls and a valve between its chambers. Blood is pumped from the heart to the gills, where it receives oxygen and gets rid of carbon dioxide. Blood then moves on to the organs of the body, where nutrients, gases, and wastes are exchanged. However, there is no division of the circulation between the respiratory organs and the rest of the body. That is, the blood travels in a circuit which takes blood from heart to gills to organs and back to the heart to start its circuitous journey again.


Frogs have a three-chambered heart, consisting of two atria and a single ventricle. Blood leaving the ventricle passes into a forked aorta, where the blood has an equal opportunity to travel through a circuit of vessels leading to the lungs or a circuit leading to the other organs. Blood returning to the heart from the lungs passes into one atrium, while blood returning from the rest of the body passes into the other. Both atria empty into the single ventricle. While this makes sure that some blood always passes to the lungs and then back to the heart, the mixing of oxygenated and deoxygenated blood in the single ventricle means the organs are not getting blood saturated with oxygen. Still, for a cold-blooded creature like the frog, the system works well.


Humans and all other mammals, as well as birds, have a four-chambered heart with two atria and two ventricles. Deoxygenated and oxygenated blood are not mixed. The four chambers ensure efficient and rapid movement of highly oxygenated blood to the organs of the body. This has helped in thermal regulation and in rapid, sustained muscle movements. We have learned much about the heart and circulatory system since Harvey’s pioneering work. Scientific research has replaced mystical spirits as the basis for medical practice. In the next part of this chapter, thanks to the work of William Harvey, we will discuss our human heart and circulation, some of the medical problems that can occur, and how advances in modern medical care allow treatment of some of these problems. Source: Roger E. Phillips, Jr.

Identification of Risk Loci with Shared Effects on Five Major Psychiatric Disorders


Findings from family and twin studies suggest that genetic contributions to psychiatric disorders do not in all cases map to present diagnostic categories. As a result, a study published in The Lancet, Early Online Publication (28 February 2013), was performed to identify specific variants underlying genetic effects shared between the five disorders in the Psychiatric Genomics Consortium: autism spectrum disorder, attention deficit-hyperactivity disorder, bipolar disorder, major depressive disorder, and schizophrenia.


The study analyzed genome-wide single-nucleotide polymorphism (SNP) data for the five disorders in 33,332 cases and 27,888 controls of European ancestory. To characterize allelic effects on each disorder, the study applied a multinomial logistic regression procedure with model selection to identify the best-fitting model of relations between genotype and phenotype. The study then examined cross-disorder effects of genome-wide significant loci previously identified for bipolar disorder and schizophrenia, and used polygenic risk-score analysis to examine such effects from a broader set of common variants. A pathway analyses was then undertaken to establish the biological associations underlying genetic overlap for the five disorders. Enrichment analysis of expression quantitative trait loci (eQTL) data was used to assess whether SNPs with cross-disorder association were enriched for regulatory SNPs in post-mortem brain-tissue samples.


Results showed that SNPs at four loci surpassed the cutoff for genome-wide significance (p<5X10-8) in the primary analysis: regions on chromosomes 3p21 and 10q24, and SNPs within two L-type voltage-gated calcium channel subunits, CACNA1C and CACNB2. Model selection analysis supported effects of these loci for several disorders. Loci previously associated with bipolar disorder or schizophrenia had variable diagnostic specificity. Polygenic risk scores showed cross-disorder associations, notably between adult-onset disorders. Pathway analysis supported a role for calcium channel signaling genes for all five disorders. Finally, SNPs with evidence of cross-disorder association were enriched for brain eQTL markers.


What this all means is that the findings show that specific SNPs are associated with a range of psychiatric disorders of childhood onset or adult onset. In particular, variation in calcium-channel activity genes seems to have pleiotropic effects on psychopathology. These results provide evidence relevant to the goal of moving beyond descriptive syndromes in psychiatry, and towards a nosology informed by disease cause.

First Grade Math Skills Set  Foundation for Later Math Ability


The basic math skill, number system knowledge, is the ability to relate a quantity to the numerical symbol that represents it, and to manipulate quantities and make calculations. This skill is the basis for all other mathematics abilities, including those necessary for functioning as an adult member of society, a concept called numeracy.


According to researchers supported by the National Institutes of Health, Children who failed to acquire a basic math skill in first grade scored far behind their peers by seventh grade on a test of the mathematical abilities needed to function in adult life. The study reported that early efforts to help children overcome difficulty in acquiring number system knowledge could have significant long-term benefits. The study noted that more than 20% of U.S. adults do not have the eighth grade math skills needed to function in the workplace.


These results are part of a long-term study of children in the Columbia, Mo., school system. Initially, first graders from 12 elementary schools were evaluated on their number system knowledge. Number system knowledge encompasses several core principles:


— Numbers represent different magnitudes (five is bigger than four).

— Number relationships stay the same, even though numbers may vary. For example, the difference between 1 and 2 is the same as the difference between 30 and 31.

— Quantities (for example, three stars) can be represented by symbolic figures (the numeral 3).

— Numbers can be broken into component parts (5 is made up of 2 and 3 or 1 and 4).


The study also evaluated such cognitive skills as memory, attention span, and general intelligence and found that by seventh grade, children who had the lowest scores on an assessment of number system knowledge in first grade lagged behind their peers. These differences in numeracy between the two groups were not related to intelligence, language skills or the method students used to make their computations.


For the testing at age 13, 180 of the students took timed assessments that included multiple-digit addition, subtraction, multiplication, and division problems; word problems; and comparisons and computations with fractions. Previous studies have shown that these tests evaluate functional numeracy — skills that adults need to join and succeed in the workplace. This might include the limited understanding of algebra needed to make change such as being able to provide an answer to a question such as: “If an item costs $1.40 and you give the clerk $2, how many quarters and how many dimes should you get back?” Other aspects of functional numeracy include the ability to manipulate fractions, as when doubling the ingredients in a recipe (for example, adding 1.5 cups water when doubling a recipe that calls for .75 cups water) or finding the center of a wall when wanting to center a painting or a shelf.


Results showed that a low score on the assessment of number system knowledge in first grade significantly increased a student’s risk of getting a low functional numeracy score as a teenager.


The study examined learning and found that first graders with the lowest scores also had the slowest growth in number system knowledge throughout that school year. Starting with poor number knowledge can put children so far behind that they never catch up.


Graphics illustrating number system knowledge and depicting the study results are available.

Primary Prevention of Cardiovascular Disease with a Mediterranean Diet


Observational cohort studies and a secondary prevention trial have shown an inverse association between adherence to the Mediterranean diet and cardiovascular risk. As a result, a randomized study, funded by the Spanish government’s Instituto de Salud Carlos III and others, and published online in the New England Journal of Medicine (25 February 2013), evaluated this diet pattern for the primary prevention of cardiovascular events.


In a multicenter trial in Spain, participants who were at high cardiovascular risk, but with no cardiovascular disease at enrollment, were randomly assigned to one of three diets: a Mediterranean diet supplemented with extra-virgin olive oil, a Mediterranean diet supplemented with mixed nuts, or a control diet (advice to reduce dietary fat). Participants received quarterly individual and group educational sessions and, depending on group assignment, free provision of extra-virgin olive oil, mixed nuts, or small nonfood gifts. The primary end point was the rate of major cardiovascular events (myocardial infarction, stroke, or death from cardiovascular causes). On the basis of the results of an interim analysis, the trial was stopped after a median follow-up of 4.8 years.


A total of 7,447 persons were enrolled (age range, 55 to 80 years); 57% were women. The two Mediterranean-diet groups had good adherence to the intervention, according to self-reported intake and biomarker analyses. A primary end-point event occurred in 288 participants. The multivariable-adjusted hazard ratios were 0.70 and 0.72 for the group assigned to a Mediterranean diet with extra-virgin olive oil (96 events) and the group assigned to a Mediterranean diet with nuts (83 events), respectively, versus the control group (109 events). No diet-related adverse effects were reported.


The authors concluded that among persons at high cardiovascular risk, a Mediterranean diet supplemented with extra-virgin olive oil or nuts reduced the incidence of major cardiovascular events.

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


Rare Disorders Without Borders: An International Strategy



Target Health is proud that it has helped its clients obtain 10 Orphan Drug designations as well as having played a key role last year supporting the approval of drugs to treat patients with Gaucher Disease and Cystic Fibrosis.


The following is based on a report by Katherine Needleman, Ph.D., Director of the Orphan Products Grants Program of FDA’s Office of Orphan Products Development posted on the FDA blog called FDA Voice


According to Dr. Needleman, the development of 200 new therapies for rare diseases and diagnostic tests for most rare diseases would alleviate untold suffering and that FDA’s Office of Orphan Products Development (OOPD) has joined a global effort to make those goals a reality by 2020.


These are the goals of the International Rare Disease Research Consortium (IRDiRC), launched by the European Commission and the U.S. National Institutes of Health in April 2011 to foster collaboration in rare disease research. FDA’s OOPD recently joined IRDiRC’s Executive Committee. When the consortium holds its first major conference in Dublin in April, top experts and researchers from around the world will share information and foster collaborations.


Some rare diseases affect only a few hundred people, and by FDA’s definition, each one affects no more than 200,000 people in the U.S. Yet taken together, about 7,000 rare diseases afflict about 30 million Americans and a similar number in Europe. In much of the world, they go undiagnosed. Often, they are debilitating or deadly. Many are genetic, so children are often victims.


On Rare Disease Day 2013 last week, the international rare disease community came together with the theme “Rare Disorders Without Borders,” and FDA continues its commitment to close collaboration with international counterparts, such as the European Medicines Agency.


FDA is the first regulatory agency to join the consortium’s Executive Committee. In addition, FDA is represented on the consortium’s Therapies Scientific Committee by Marc Walton, M.D., Ph.D., in FDA’s Center for Drug Evaluation and Research. FDA’s goal is to bring regulatory scientific perspectives that help develop great research ideas into great products that meet regulatory approval standards for safety and effectiveness.


FDA has been working to change the orphan status of rare diseases since 1983, with the passage of the Orphan Drug Act. Since then, FDA has approved over 400 products for the treatment of rare diseases, compared to only 10 developed by industry in the decade before the act. OOPD’s grant program uses its annual budget of approximately $14 million to fund top scored clinical trials of rare disease treatments. The grants program has been successful, as at least 49 OOPD grants supported clinical trials that contributed to agency approval of these products for rare diseases. Still, for most rare diseases, there are no treatments, or definitive diagnostic tests. Recent progress in human genomics and newly emerging sciences increase the prospect for treatments or even cures. A new generation of therapies even shows promise for changing the defective genes that result in some rare diseases. These are among the topics that will be addressed at the upcoming conference.


Sweet Potato Black Bean Casserole




2 pound(s) sweet potato(es), scrubbed and dried

30 oz. can of black beans, rinsed and dried well

15 oz. can of diced tomatoes, or use your own home made, or your own marinara sauce

1 bunch(es) spinach (must wash several times to get sand out; then dry on paper towels)

1 box cremini mushrooms, clean with cloth and slice

1 onion, chopped

1 garlic clove, juiced

1 Tablespoon ground coriander or garam masala

1 Tablespoon Ground Cumin Seed or 1 teaspoon Turmeric

1 or 2 cup(s) shredded part-skim mozzarella cheese (to your taste)




1.  slice sweet potatoes ~1/4 inch thick & quarter

2.  spray casserole dish and lay down a layer of sweet potato slices

3.  cook beans, mushrooms, onion, garlic juice, tomatoes & spinach in a skillet, season with all of the above spices)

4.  layer half of bean mixture on top of sweet potatoes. layer half of the cheese on top, then more sweet potatoes, the rest of the bean mixture, and the rest of the sweet potatoes.

5.  bake, covered, for 25 minutes at 400. Uncover, top with rest of cheese, and bake for 25 more minutes.


This casserole would be good to serve with a simple poached, broiled or baked salmon, some crusty warm 7-grain rolls or bread (dip in your best olive oil), a simple tossed salad, fruit and cheese platter and a well-chilled Sauvignon Blanc.



Medical Miracles – Financial Catastrophes


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



In a timely and sadly necessary exposure of cruel gaps in our health care system, Steven Brill, in an article titled “Bitter Pill: Why Medical Bills Are Killing Us” appearing in Time Magazine, has unmasked what remains among the most problematic realities in health care delivery. Despite all of the heated rhetoric, frantic activity and ultimately legislation during the past several years, there are Americans, among them those who believe themselves adequately insured, who remain separated by one serious illness from financial ruin.


How can this be?


The fundamental problem is our persistent illusion that the health care market functions, should function, or is capable of functioning like typical markets. Sadly, many of our political leaders who by virtue of their education, experience, and sophistication should know better, continue to maintain that a patient entering an emergency room with chest pain, fearing he is about to die of a heart attack, is similar in thought processes, decision making capabilities, access to information and freedom, to select among various options to that same “consumer” entering a car dealership to purchase an automobile or an electronics store to purchase a smart phone.


While this premise defies common sense, it nevertheless seems to guide many decision makers who persistently maintain that we must allow market forces to work their magic in health care, ultimately driving consumers to make cost effective decisions based upon their natural desire to maximize the utility of their resources.


Brill discloses that the consumer/patient, upon entry into the health system, is rendered helpless, compelled to provide a virtual blank check to the providing facility ceding both unlimited credit and unchecked decision making authority. An analogous situation would require that upon entry into an automobile dealership a customer was forced to authorize the dealer to select his model & options, purchase an extended warranty, and if the vehicle were to be financed determine the length and interest rate of the loan. Finally, the customer would not be told the price of the vehicle to be purchased (until after the bill arrives). The customer, however, would retain the responsibility of making whatever payments were ultimately required by this ‘‘deal”.


As Brill illustrates through a series of compelling vignettes, this is actually how our health care system functions for some patients (it is not possible to determine the frequency from the article, but even one instance is too many). Health emergencies, unpredictable and profoundly stressful by definition, have therefore (at least potentially) become cause for profound financial anguish and in some instances frank financial ruin to precisely the cohort of individuals who most politicians claim they want to protect, the middle class. It is members of this group who may not qualify for public assistance, are insufficiently wealthy to shoulder the costs alone, have sufficient assets to be the target of creditors, and strive to play by the rules, who are most vulnerable.


This reality is simply indefensible; despite the dissembling explanations of the array of providers of services in the system.


The Affordable Care Act may ameliorate some of these problems, but likely not all.


Sometimes problems are simpler to solve than they seem; often defining the problem precisely can help. No one, especially one who is insured, should be forced into bankruptcy due to legitimate health needs. We could protect patients and providers financially through a national system of catastrophic coverage with maximum out of pocket costs based upon income. There are undoubtedly many other viable solutions.


The key is deciding that we are done ruining responsible people whose only transgression is to become ill. Serious illness is bad enough; the health system should not be in the business of compounding tragedy. This is a problem than can, and for moral reasons must be fixed.


We must remember the admonition – Primum Non Nocere (First, Do No Harm).