Target Health Presenting at Meeting on Disruptive Innovations
Target Health Inc. will be sponsoring and presenting at the 2nd Annual Disruptive Innovations to Advance Clinical Trials for Pharma, Biologics and Devices event which is being held at The Fairmont Copley Plaza Hotel, Boston, September 13-14, 2012. The conference is designed for drug and device development innovative thinkers who are determined to reinvent clinical trials. It is an outcomes-focused program that not only delves deeply into the key strategic factors impeding clinical trial productivity, but also endeavors to connect the change-makers who will share their results and outcomes.
Dr. Jules T. Mitchel, who is on the DPharm Advisory Board of the conference, will provide an update on the collaboration between Ferring Pharmaceuticals and Target Health Inc. (eCRO) on its approach to the paperless clinical trial including the use of Target e*CTR (eClinical trial record) as an eSource tool and Target Document for the electronic Trial Master File (eTMF). Go to the meeting website and get a 25% discount off the registration fee with code SFD.
Dr. Mitchel is also speaking at a concurrent conference on Executing Clinical Trials – How to Globalize Your Study for Clinical Success. The topic of his panel is Risk-based Monitoring – What Does it Mean for Your Global Study? How Different Organizations are Adapting to a Risk Based Approach to Monitoring in Their Global Studies.
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 www.targethealth.com
Gene That Predicts Happiness in Women Discovered
A new study has found a gene that appears to make women happy, but it doesn’t work for men. The finding may help explain why women are often happier than men. (Credit: © Yuri Arcurs / Fotolia)
A new study has found a gene that appears to make women happy, but it doesn’t work for 1) ___. According to the authors, the finding may help explain why women are often happier than men. Scientists at the University of South Florida (USF), the National Institutes of Health (NIH), Columbia University and the New York State Psychiatric Institute reported that the low-expression form of the gene monoamine oxidase A (MAOA) is associated with higher self-reported happiness in 2) ___. No such association was found in men.
The findings appear online in the journal Progress in Neuro-Psychopharmacology & Biological Psychiatry.
“This is the first 3) ___ gene for women,” said lead author Henian Chen, MD, PhD, associate professor in the Department of Epidemiology and Biostatistics, USF College of Public Health. “I was surprised by the result, because low expression of MAOA has been related to some negative outcomes like alcoholism, aggressiveness and antisocial behavior,” said Chen, who directs the Biostatistics Core at the USF Health Morsani College of Medicine’s Clinical and Translational Sciences Institute. “It’s even called the warrior gene by some scientists, but, at least for women, our study points to a brighter side of this 4) ___.” While they experience higher rates of mood and anxiety disorders, women tend to report greater overall life happiness than do men. The reason for this remains unclear, Chen said. “This new finding may help us to explain the 5) ___ difference and provide more insight into the link between specific genes and human happiness.”
The MAOA gene regulates the activity of an enzyme that breaks down serontin, dopamine and other neurotransmitters in the 6) ___ — the same “feel-good” chemicals targeted by many antidepressants. The low-expression version of the MAOA gene promotes higher levels of monoamine, which allows larger amounts of these neurotransmitters to stay in the brain and boost mood. The study analyzed data from a population-based sample of 345 individuals — 193 women and 152 men — participating in Children in the Community, a longitudinal 7) ___ health study. The DNA of study subjects had been analyzed for MAOA gene variation and their self-reported happiness was scored by a widely used and validated scale. After controlling for various factors, ranging from age and education to income, the study found that women with the low-expression type of MAOA were significantly happier than others. Compared to women with no copies of the low-expression version of the MAOA gene, women with one copy scored higher on the happiness scale and those with 8) ___ copies increased their score even more. While a substantial number of men carried a copy of the “happy” version of the MAOA gene, they reported no more happiness than those without it.
So, why the genetic gender gap in feeling good?
The authors suspect the difference may be explained in part by the hormone 9) ___, found in much smaller amounts in women than in men. Chen and his co-authors suggest that testosterone may cancel out the positive effect of MAOA on happiness in men. The potential benefit of MAOA in boys could wane as testosterone levels rise with puberty, Chen said. “Maybe men are happier before adolescence because their testosterone levels are 10) ___.” Chen emphasizes that more research is needed to identify which specific genes influence resilience and subjective well-being, especially since studies of twins estimate genetic factors account for 35 to 50% of the variance in human happiness.
While happiness is not determined by a single gene, there is likely a set of genes that, along with life experiences, shape our individual happiness levels, Chen said. “I think the time is right for more 11) ___ studies that focus on well-being and happiness.” “Certainly it could be argued that how well-being is enhanced deserves at least as much attention as how mental 12) ___ arise; however, such knowledge remains limited.”
ANSWERS: 1) men; 2) women; 3) happiness; 4) gene; 5) gender; 6) brain; 7) mental; 8) two; 9) testosterone; 10) lower; 11) genetic; 12) disorders
Tracing the Path of Jewish Medical Pioneers
The Jewish Consumptives’ Relief Society, one of many Jewish health groups started in New York, used sunlight to help treat tuberculosis in Colorado about 1930. Photo Credit: Beck Archives, Special Collections and Archives, Penrose Library and Center for Judaic Studies, University of Denver
The young man who applied to medical school in the spring of 1933 had graduated from Dartmouth College with good grades, a keen interest in medicine and, according to the university official who interviewed him, a nice sense of humor. The application did not ask about religion, but the interviewer surmised it. “Probably Jewish,” he wrote in a scribbled evaluation, “but no unpleasant evidence of it.” The handwritten note was found in the admissions files of the College of Physicians and Surgeons at Columbia University. After the implementation of quotas, the proportion of Jews in the student body fell to less than 5% in 1938 from nearly half in 1920. The note is displayed in an exhibition called “Trail of the Magic Bullet: The Jewish Encounter With Modern Medicine, 1860-1960,” on view at Yeshiva University Museum in Manhattan. The exhibition offers a rare look at a topic few patients ever stop to consider: the emergence of European and American Jews as innovators in medicine, despite their status as outsiders frequently scorned by the medical establishment.
While some religions place ultimate responsibility for healing in divine hands, “Jews don’t see a conflict between faith and medicine,” said Alan M. Kraut, a professor of history at American University who helped put together the exhibition and has written extensively about immigration and health. “The healer is seen as one of God’s instruments, not a competing force,” he said. “The physician is someone held in the highest esteem, doing God’s work – preserving life.”
During the Middle Ages, European Jews were instrumental in the spread of medical knowledge, translating many important early medical treatises from Arabic into Hebrew and other languages. One of the books in the exhibition is said to be the first medical textbook printed in Hebrew, a translation of a treatise written by the Persian physician-philosopher Avicenna in the 11th century. But Jews were not admitted into most medical schools in Europe; they learned medicine through apprenticeships or were self-taught, said Dr. Edward I. Reichman, a physician and rabbi who practices at Montefiore Medical Center in the Bronx and teaches medical ethics. One university in Padua, Italy, admitted Jews in the 1500s, but charged them higher fees than other students.
In 1598, a papal edict issued by Pope Clement VIII reaffirmed edicts by previous popes that prohibited Jewish doctors from treating Christians and barred Christians from seeking treatment from Jewish physicians. There were exceptions, however. “Almost every pope in history had a personal physician who was Jewish,” Dr. Reichman noted. In the late 1800s, medical schools in Europe started opening their doors to Jews, and many entered the profession, including some of the first women to study medicine. By the early 20th century, half of the physicians in Berlin were Jewish, as were 60% of the physicians in Vienna and 70% of the physicians in Warsaw.
Because they were barred entry to established specialties like surgery, Jews flocked to new, less prestigious fields, making their marks in areas like psychiatry (psychoanalysis was for a while called the “Jewish science”), dermatology, neurology, immunology, pathology and gynecology.
Few escaped the pervasive prejudice, however. In the early 1900s, Dr. Paul Ehrlich, a German Jew who discovered a treatment for syphilis and is considered the father of chemotherapy, popularized the term “magic bullet” to describe a medical compound that would “aim exclusively at the dangerous intruding parasites” yet not “touch the organism itself.” Dr. Ehrlich was awarded the Nobel Prize in 1908 and that posting was placed at the University of Frankfurt in 1914, the year of its founding. In the 1930s, as the Nazis came to power, his name was removed from textbooks and taken off Frankfurt’s street signs. Paul-Ehrlich-Strasse regained its name only after World War II.
Many of New York’s most familiar medical institutions have their roots in the late 19th century. An influx of poor Jewish immigrants from Eastern Europe to the Lower East Side raised concern over cramped living conditions in the tenements, leading to the development of several Jewish health organizations in New York, like the Jewish Consumptives’ Relief Society, and the establishment of Jewish hospitals, open to patients of all religions. As the importance of early child health became clear, the New York Society for Ethical Culture focused on maternal health and pre- and postnatal infant care, using graphic posters with Yiddish captions to encourage breast-feeding and to teach basic hygiene. In the 1920s and 1930s, as American medical schools like Columbia cut the number of Jews they admitted, many went to Scotland to study. The doors to hospital-based training programs were closed, but new Jewish hospitals absorbed the trainees. The Albert Einstein College of Medicine of Yeshiva University, a sponsor of the exhibition, was established in the 1950s.
A last section in the exhibition grapples with Jewish medical ethics and religious approaches to questions posed by modern medical science, from genetic testing and stem cell research to end-of-life issues and organ donation. Whether Jewish physicians were observant or not, their practices incorporated teachings from around the globe, said Bert Hansen, a historian of science and medicine at Baruch College and an exhibition adviser. “There was never a ‘Jewish medicine’ the way there was Chinese or Eastern medicine,” he said. “Jewish doctors wanted to learn and then use the best medical techniques and thought of the time.” Source: The New York Times, by Roni Caryn Rabin
Comment from Mark L. Horn MD, MPH, Chief Medical Officer at Target Health Inc., Staff Physician at Mt Sinai Hospital, New York City
“Irrespective of antisemitism, or perhaps in part as a consequence of it, a group of Jewish philanthropists established the Jews’ Hospital in 1852, which subsequently became the Mount Sinai Hospital and ultimately the Mount Sinai Hospital and School of Medicine. Throughout its history the institution has been a source of both clinical and research excellence. Ironically, and this story may be apocryphal, the hospital may have been the inadvertant beneficiary of antisemitism since discrimination by other prestigious institutions made Mount Sinai the destination of choice for training by talented Jewish physicians. Once discrimination ebbed, their opportunities increased as did the competition for their talents.”
Compounds that Activate Key Cancer Enzyme Interfere with Tumor Formation
It has been known for decades that cancer cells use more glucose than healthy cells, feeding the growth of some types of tumors. Now, a team, including members from the National Institutes of Health’s new National Center for Advancing Translational Sciences (NCATS) has identified compounds that delay the formation of tumors in mice, by targeting a key enzyme that governs how cancer cells use glucose and its metabolites. The study was published in the advance online publication of Nature Chemical Biology (26 August 2012).
All cells use an enzyme called pyruvate kinase to derive energy from glucose. Recent studies have shown that cancer cells preferentially use one form of pyruvate kinase, called PKM2, which uses glucose to make additional cancer cells instead of energy. This altered metabolic state appears to be a fundamental aspect of many cancers, and reversing the process represents a new opportunity for cancer treatment. In the study report, the authors describe the identification of molecular compounds that activate PKM2, correct the way human cancer cells use glucose, and delay tumor development and decrease tumor size in mice. The results support PKM2 activation as a potential therapeutic strategy for cancer. However, the authors emphasized there is much more work needed to understand the implications of their findings for humans, such as determining what types of tumors might be sensitive to PKM2 activation.
The study of cancer cell metabolism, pioneered by Nobel Laureate Otto Warburg in the early part of the 20th century, has witnessed a resurgence in research activity in recent years. New compound tools will be critical to dissecting the complex pathways that govern how cancer cells utilize nutrients such as glucose that provide the molecular building blocks to support rampant cell growth. The PKM2 activators detailed in the paper are among the first pharmacological compounds identified that will enable researchers to dig deeper into this key problem.
To test that theory, a collaboration was formed in 2008 to identify PKM2 activators, laying the foundation for the current study. Compounds were discovered using a high-throughput screening robotic system and then optimized the compounds in order to yield molecules with the needed pharmacological activity and the required physical properties for experimentation. In the new study, the authors focused their attention on how the compounds activate PKM2 and the effect this activation has on the formation of tumors. Hints as to the consequences of PKM2 activation were derived from experiments involving PKM1, a highly related enzyme of PKM2 that is found in healthy cells in an active state.
The unique mechanism of PKM2 activators prompted the authors to dig deeper into the metabolic consequences of activating PKM2 by looking at the ability of the activators to mimic the results associating PKM1 expression with delayed tumor development. Aided by researchers at Agios Pharmaceuticals, Cambridge, Mass., it was determined that one PKM2 activator, TEPP-46, could be used in a mouse study. The mice were given the compound, and it hindered tumor development and reduced tumor size.
Stresses of Poverty May Impair Learning Ability in Young Children
High levels of stress hormones influence the developing circuitry of children’s brains, inhibiting such higher cognitive functions such as planning, impulse and emotional control, and attention. Known collectively as executive functions, these mental abilities are important for academic success.
According to an article published in the September/October issue of Scientific American Mind (2012), the stresses of poverty — such as crowded conditions, financial worry, and lack of adequate child care — lead to impaired learning ability in children from impoverished backgrounds. The theory is based on several years of studies matching stress hormone levels to behavioral and school readiness test results in young children from impoverished backgrounds. Further, the theory holds, finding ways to reduce stress in the home and school environment could improve children’s wellbeing and allow them to be more successful academically.
The authors conclude that this altered stress response and its effect on executive function helps to explain one way in which poverty affects children’s development of school readiness skills and later classroom performance. Although poverty is considered a major source of stress, the findings also suggest that other sources of stress may affect children in all income groups, for example, from divorce, harsh parenting, or struggles with a learning disability.
During the course of their research, the authors measured children’s levels of cortisol, a hormone the body releases in response to stress. With minor stress, a modest increase followed by a decrease in cortisol over time is associated with improved performance on complex tasks. However, the authors explained, at high levels of stress, particularly over a long period of time, cortisol can be sustained at high or low levels or even become blunted, actually decreasing in response to challenges.
In one study, the authors tested 170 4-year-old children who were attending Head Start — the preschool program for children in poverty. The authors analyzed levels of cortisol in the children’s saliva before, during and after the testing, as a measure of the stress the children experienced when participating in the tests. The authors also assessed children’s executive function, asking children to tap a peg twice, after the researchers tapped it once, and vice versa, and to identify different ways in which pictures of items were similar in terms of shape, color, and size. In this study, it was found that children exhibiting the typical cortisol response pattern had higher levels of executive function. Teachers also rated these children as being high in self-control in the classroom. In contrast, children exhibiting a flat low or high response or a blunted response had low levels of executive function and were rated by teachers as having poor self-regulation.
The authors then reassessed the children in kindergarten. Those who had high executive function scores in the original study tended to have the highest math scores. Conversely, the children with high cortisol levels and low executive function were likely to have difficulty with math, reading, and writing. The authors next sought to identify which aspects of poverty might be particularly stressful for children and cited earlier research showing that parents living in poverty are more likely than are other parents to be concerned with eliciting obedience from their children by disciplining them.
For about seven years, the researchers have been observing more than 1,200 children and their families, as part of the Family Life Project, an NICHD-funded study of the effects of growing up in rural poverty. Most of the children are from poor rural communities in Appalachia and the Deep South. In a study published about their observations, the authors analyzed video recordings of mothers interacting with their children during play sessions. Children whose mothers engaged in scaffolding — creating opportunities to accomplish small tasks, like stacking blocks — had lower cortisol levels and were more attentive. In contrast, the children of mothers who were more authoritative — completing the task for their children, or restricting the children’s activity — had higher cortisol levels, suggesting that the children had higher stress levels. This association between parenting style and cortisol level was present when the children were 7 months old, and again when they were 15 months old. In a subsequent study, the authors sought to ascertain the influence of poverty on children’s executive functioning. They found that the more impoverished the family, the less likely the parents were to engage in the scaffolding approach. The children of these parents were more likely to have elevated cortisol levels in response to stress. And the children with high cortisol levels were more likely to have poor executive function.
The authors are now testing a new program that teaches parents how to engage in scaffolding behavior — to provide opportunities for their children to learn while providing supportive and loving care. The program is also testing a new curriculum that gives preschoolers and kindergarteners more control over their learning activities. In a year, the researchers will compare the children’s cortisol levels and executive functioning.
Calorie Restriction Does Not Affect Survival But Does Suggest Some Benefits
Calorie restriction research has a long history. The first finding came in the 1930s, when investigators observed laboratory rats and mice lived up to 40% longer when fed a calorie-restricted diet. Subsequent research has cited calorie restriction as extending lifespan of yeast, worms, flies and some strains of mice. But other studies have not shown a longevity benefit. For example, in studies of certain strains of mice, calorie restriction on average had no effect on lifespan. Some of these mice actually had a shorter lifespan when given a calorie-restricted diet. To date, research does not provide evidence that calorie restriction is an appropriate age regulator in humans. Currently, limited human studies are under way to test the effectiveness and safety of calorie restriction in people.
According to an article published online in Nature (29 August 2012), it was observed that calorie restriction — a diet comprised of approximately 30% fewer calories, but with the same nutrients of a standard diet– does not extend years of life or reduce age-related deaths in a 23-year study of rhesus monkeys. However, calorie restriction did extend certain aspects of health. The survival results in the study current study differ from those published in 2009 by NIA-supported investigators at the University of Wisconsin-Madison. The Wisconsin study followed two groups of rhesus monkeys for 20 years and found that monkeys on a calorie-restricted diet lived longer than those on a standard diet.
Beyond longevity, the parallel NIA and Wisconsin studies have reported similar beneficial health effects of calorie-restriction. Both studies found that certain age-related diseases — including diabetes, arthritis, diverticulosis and cardiovascular problems — occurred at an earlier age in monkeys on the standard diet compared to those on calorie restriction. However, this observation was not statistically significant in the NIA study. The NIA investigators did find that monkeys started on calorie restriction at an early age had a statistically significant reduction in cancer incidence.
The NIA study also found that while calorie restriction had a beneficial effect on several measures of metabolic health and function in monkeys who were started on the special diet regimen during old age (at 16 to 23 years), it did not have the same positive outcome for monkeys started on calorie restriction at a young age (less than 14 years). In the Wisconsin study, all the monkeys were 7 to 14 years when started on calorie restriction.
Differences in the monkeys’ meal and other nutritional factors were cited as possible explanations for NIA’s and Wisconsin’s different outcomes. Both studies used a similar percentage of calorie restriction with their intervention groups; however, the Wisconsin monkeys in both the calorie restricted and control groups were eating more and weighed more than the matched NIA monkeys.
NIA’s food had a natural ingredient base, while Wisconsin opted for a purified diet. Purified diets generally lack trace dietary chemicals and minerals that could affect an animal’s health. Each ingredient of a purified diet provides a specific nutrient and minerals or vitamins must be added separately. Natural-ingredient diets have risk of variation between batches, but are considered by some to be more complete than purified diets. NIA and Wisconsin also used different sources for proteins, fat and carbohydrates, as well as different approaches to vitamin and mineral supplementation. Genetics may also offer another possible reason for the differing results. NIA monkeys had a greater genetic diversity, originating from China and India. Wisconsin’s monkeys came only from an Indian colony.
TARGET HEALTH excels in Regulatory Affairs. Each week we highlight new information in this challenging area.
FDA Approves New Treatment for a Type of Late Stage Prostate Cancer
Prostate cancer forms in a gland in the male reproductive system found below the bladder and in front of the rectum. The male hormone testosterone stimulates the prostate tumors to grow. According to the National Cancer Institute, an estimated 241,740 men will be diagnosed with prostate cancer and 28,170 will die from the disease in 2012.
The FDA has approved Xtandi (enzalutamide) to treat men with late-stage (metastatic) castration-resistant prostate cancer that has spread or recurred, even with medical or surgical therapy to minimize testosterone. Xtandi was approved for prostate cancer patients previously treated with docetaxel, another anti-cancer treatment. Xtandi was reviewed under the FDA’s priority review program. The program provides for an expedited six-month review for drugs that may offer major advances in treatment or that provide a treatment when no adequate therapy exists. Xtandi received FDA approval three months ahead of the product’s prescription drug user fee goal date of Nov. 22, 2012.
The safety and effectiveness of Xtandi was evaluated in a study of 1,199 patients with metastatic castration-resistant prostate cancer who had received prior treatment with docetaxel. The study was designed to measure overall survival (the length of time before death) in men receiving Xtandi compared with men receiving placebo. The median overall survival for patients receiving Xtandi was 18.4 months, compared with 13.6 months for the patients who received placebo.
The most common side effects observed in study participants taking Xtandi were weakness or fatigue, back pain, diarrhea, joint pain, hot flush, tissue swelling, musculoskeletal pain, headache, upper respiratory infections, dizziness, spinal cord compression and cauda equina syndrome, muscular weakness, difficulty sleeping, lower respiratory infections, blood in urine, tingling sensation, anxiety, and high blood pressure. Seizures occurred in approximately 1% of those receiving Xtandi. Patients in the study who had a seizure stopped Xtandi therapy. The clinical study excluded patients with a history of seizure, an underlying brain injury with loss of consciousness, a temporary decrease in blood to the brain within the past 12 months, a stroke, brain metastases, an abnormal connection of the arteries and veins in the brain, or patients taking medications that may lower the seizure threshold. The safety of Xtandi is unknown in patients with these conditions.
Xtandi will be co-marketed by Astellas Pharma U.S., Inc. of Northbrook, IL and Medivation, Inc. of San Francisco, CA.
We got sick of store-bought cole slaw, so we experimented and came up with this easy recipe that we love. Now we never buy it.
½ Bunch Fresh Dill
½ Red Onion
1 Tablespoon Cider Vinegar
3-4 Tablespoons Kraft Mayo (depending on size of Cabbage). Feel free to substitute low-fat mayo or any variety you like.
Use a good mandolin and be careful of the sharp blade. The thinner you can get these ingredients, the better the flavors are.
Wash everything well and pat dry with paper towels.
Set the blade of your mandolin to as thin as possible. With a knife, cut cabbage in chunks that you can handle as you slice it through the mandolin. Put the thinly sliced cabbage into a salad bowl.
With the mandolin, slice the onion as thin as possible and then take the slices and chop them even more with a sharp knife. Put into the salad bowl
With a hand grater, grate the carrot. Then take the grated pieces and cut them even smaller with a sharp knife. Put carrot into salad bowl
Discard any stems from the dill and with a sharp knife, chop it into very fine pieces and put into the salad bowl.
Stir all the veggies in the salad bowl and then add the cider vinegar and stir it through.
Now add the mayo slowly, one tablespoon at a time and stir it in. Depending on the amount of veggies, decide how much mayo is needed. Taste as you go until you get the consistency and the flavor you want.