2012 Fundamentals of the Bioscience Industry Program for Students and Professionals

 

 

Dr. Jules T. Mitchel, President of Target Health Inc., is again partnering with Dr. Eric Vieria of the Office of Technology and Business Development of the Mt. Sinai School of Medicine as Directors of The 2012 Fundamentals of the Bioscience Industry Program. This program is a one semester, evening program in New York City and Stony Brook, LI, created by the Center for Biotechnology at SUNY Stony Brook. The program offers students the opportunity to gain a comprehensive understanding of the Bioscience Industry from target identification through commercial application. Benefits of the program include:

 

  1. Increase marketability for participants by expanding their education beyond the typical classroom
  2. Hands on work with technologies to advance an invention through
  3. Connections made with industry leaders through on going classroom interaction
  4. Access to a network of over 250 program alumni providing career opportunities, mentoring and social interactions

 

To learn more about the program and its opportunities visit:www.fobip.org. Scholarships are available to all graduate students and post-docs that will cover up to 50% of program costs. Application Deadline December 16, 2011. For more information and questions, contact Kate Hutchinson or call 631-632-8521.

 

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

Some People Can Hallucinate Colors at Will

 

Scientists at the University of Hull have found that some people have the ability to hallucinate colors at will — even without the help of hypnosis. (Credit: © Paul Herbert / Fotolia)

 

 

Scientists at the University of Hull, in Yorkshire, England, have found that some people have the ability to hallucinate 1) ___ at will — even without the help of hypnosis. The study, published this week in the journal Consciousness and Cognition, was carried out in the Department of Psychology at the University of Hull. It focused on a group of people that had shown themselves to be ‘highly suggestible’ in 2) ___. The subjects were asked to look at a series of monochrome patterns and to see color in them. They were tested under hypnosis and without hypnosis and both times reported that they were able to see colors. Individuals’ reactions to the patterns were also captured using an 3) ___ scanner, which enabled the researchers to monitor differences in brain activity between the suggestible and non-suggestible subjects. The results of the research, showed significant changes in brain activity in areas of the brain responsible for 4) ___ perception among the suggestible subjects only.

 

Professor Giuliana Mazzoni, lead researcher on the project says: “These are very talented people. They can change their 5) ___ and experience of the world in ways that the rest of us cannot.” The ability to change experience at will can be very useful. Research has shown that hypnotic suggestions can be used to block 6) ___ and increase the effectiveness of psychotherapy. It has always been assumed that hypnosis was needed for these effects to occur, but the new study suggests that this is not true. Although hypnosis does seem to heighten the subjects’ ability to see color, the suggestible subjects were also able to see colors and change their brain activity even without the help of hypnosis. The MRI scans also showed clearly that although it was not necessary for the subjects to be under hypnosis to be able to perceive colors in the tests, it was evident that hypnosis increased the ability of the subjects to experience these effects.

 

Dr William McGeown, who also contributed to the study, says: “Many people are 7) ___ of hypnosis, although it appears to be very effective in helping with certain medical interventions, particularly pain control. The work we have been doing shows that certain people may benefit from suggestion without the need for hypnosis.”

 

The study, which was partially funded by the BBC, used a control group formed of less suggestible people, or people less likely to respond to hypnosis. It was found that this group of people were not able to 8) ___ color and, again, these reported results were supported by MRI scans.

 

ANSWERS: 1) colors; 2) hypnosis; 3) MRI; 4) visual; 5) perception; 6) pain; 7) afraid; 8) hallucinate

 

Charles Byrne 1761 – 1783 (“The Irish Giant”)

 

Charles Byrne, with George Cranstoun, a dwarf, and three other men, 1794.

 

 

The skeleton of Charles Byrne, Professor Márta Korbonits and patient Brendan Holland. Charles Byrne and Brendan Holland share an identical AIP mutation. The connection between these two giants has also been the subject of a BBC documentary.

 

 

Charles Byrne (1761-1783), also known as Charles O’Brien or “The Irish Giant”, was a human curiosity in London in the 1780s. Byrne’s exact height is of some conjecture, but most accounts refer to him as from 2.48 m (8’2”) to 2.54 m (8’4”) tall; however, skeletal evidence places him at just over 2.31 m (7’7”). Little is known of Byrne’s family other than that his parents were ordinary people, and that they were not unusually tall.At the age of 19 Byrne traveled to London to seek his fortune in a sideshow. He found work at Cox’s Museum, an establishment not unlike P. T. Barnum’s American Museum. By 1782, he soon became the toast of the town as, “the modern living Colossus, or wonderful Irish Giant.”

 

Fame and wealth soon overtook Byrne, and he took to drinking excessively. According to newspaper reports he was out drinking when his pocket was picked of his 700-pound life savings. Inconsolable, he tried to drown his sorrows in drink and died in June 1783, at the age of twenty-two. It was rumored that he was so afraid that doctors would dissect his corpse that on his deathbed he arranged with friends to seal his body in a lead coffin, for burial at sea. But, while his casket was buried at sea, Byrne’s body was not in it. The undertaker had been bribed and the body removed from the coffin. Competition among anatomists to obtain the body was widely reported in the press, driving up the price. John Hunter obtained the body for a sum rumored to be over £500. To avoid detection, Hunter hurriedly chopped the body into pieces, and boiled it down into the bones. Only after four years did Hunter admit to having the skeleton of Charles Byrne. In Joshua Reynolds’s famous portrait of Hunter, the legs of a giant skeleton, thought to be Byrne’s, can be seen in the background. Byrne’s skeleton can still be found today on display in the Hunterian Museum at the Royal College of Surgeons in London.

 

One journal allegedly states that on his death, “The whole tribe of surgeons put in a claim for the poor departed Irishman and surrounded his house just as harpooners would an enormous whale.” The American surgeon Harvey Cushing studied Byrne’s bones, removed the top of the skull, and in 1909 and found that Byrne had had a pituitary tumor based on an enlarged pituitary fossa.

 

In 1998, author Hilary Mantel wrote a fictionalized novel of his life in The Giant, O’Brien. The plot of the novel focused on the battle between the revolution of science and the ways of poem and song. O’Brien (Byrne) was portrayed as a man whose faith was in tales of kings and the little people, while his polar opposite John Hunter was portrayed as at the dawn of the scientific age, destroying all that is old and cherished. In 2011, British and German researchers determined the cause of Byrne’s gigantism. They extracted DNA from Byrne’s teeth and found that he had a rare mutation in his AIP gene that is involved in pituitary tumors. This rare and strange gene mutation, discovered only in 2006. The researchers then found the mutation in four families from Northern Ireland, near where Mr. Byrne was born. Following a hunch, they decided to ask whether Mr. Byrne had had the mutation, too, and whether the mutation indicated that the four families were related to him. Their hunch was right. The researchers inferred that Byrne and these families had a common ancestor about 57 to 66 generations ago (1425 to 1650 years ago).

 

The group, led by Dr. Marta Korbonits, professor of endocrinology and metabolism at Barts and the London School of Medicine and Dentistry, reports its finding in Thursday’s issue of The New England Journal of Medicine.

 

Symptom-producing pituitary tumors are rare, and those caused by an inherited mutated gene are rarer still. At most only 5% of people with pituitary tumors have them in their families. The tumors can lead to disfigurement – patients develop bulging foreheads and large jaws, hands and feet – and chronic severe headaches. They can also cause visual problems, because the tumor presses on the optic nerve. They may even cause milk secretion, because the tumor can secrete prolactin, a hormone that is needed for fertility and to produce milk in the breasts. Usually, tumors that secrete growth hormone start to grow in adulthood, after people have reached their full height. But when tumors start growing in children or adolescents – as they do with many patients with the mutated gene – they can result in gigantism because they make the gland churn out growth hormone, prodding bones to keep growing. Pituitary tumors are of great interest to researchers because they grow very slowly and almost never spread elsewhere in the body.

 

Dr. Shlomo Melmed, a pituitary tumor researcher at Cedars-Sinai Medical Center in Los Angeles, explained that the tumor cells undergo premature aging. “We think it might be protective,” Dr. Melmed said, a reason the tumor does not spread. The involvement of the gene, known as AIP, in pituitary tumors is a surprise, researchers say. Mutations in the gene are associated with about 20% of inherited pituitary tumors when no other organ is involved. But it is not clear why mutations in this gene, which seems to be involved in metabolism – possibly to detoxify chemicals – can cause tumors or how these tumors form.

 

Dr. Korbonits said she had been aware of the Irish Giant because of her work on pituitary tumors. She suspected he might have had the AIP mutation when she saw a drawing of him standing with twin brothers who also were giants, who came from a nearby village, and who were said to be related to Mr. Byrne. That, she said, “suggested it was a genetic disease.” And she had found the gene in members of four families from the same region of Ireland. Dr. Korbonits wrote to the Hunterian Museum, where Mr. Byrne’s skeleton is still displayed, and asked to test the giant’s DNA, and then she and her colleagues removed two of his molars. She enlisted the help of an expert on ancient DNA, Joachim Burger of Gutenberg University in Mainz, Germany, to extract DNA from the giant’s teeth. She was worried that the DNA might be too degraded to analyze — after all, the giant’s corpse had been boiled in acid and then displayed in a museum for a couple of centuries.

 

“It was not clear at all that we would have suitable DNA,” Dr. Korbonits said. The DNA turned out to be broken in many pieces, but it could still be analyzed. The investigators calculated that the giant and the four contemporary Irish families had a common ancestor who lived about 1,500 years ago. And, they report, there are probably 200 to 300 people living today who have inherited that same mutation. One is Brendan Holland, a 58-year-old Irishman who sells mining equipment. Mr. Holland started growing excessively when he was 13. After the AIP gene mutation was discovered in 2006, Dr. Korbonits asked to test Mr. Holland to see if he had it. He did. Then, Mr. Holland said, she started suggesting he might be related to the giant. “She was asking me pointed questions about where he lived and where I lived,” Mr. Holland said. “Then she said, ‘I think it is possible that you and this chap are related. With the giant’s DNA analysis, it turned out that Dr. Korbonits was right. Mr. Holland says he was touched thinking about the giant’s life, knowing how hard it is to be so tall and the subject of barbs and jeers.

 

Irish king Brian Boru who died in 1014 was himself a giant.

4 Medications Drive Emergency Hospitalizations for Adverse Drug Events in Older Americans

 

 

Adverse drug events are important preventable causes of hospitalization in older adults. However, nationally representative data on adverse drug events that result in hospitalization in this population have been limited. As a result, a study published in the New England Journal of Medicine (2011;365:2002-2012), evaluated adverse-event data from the National Electronic Injury Surveillance System-Cooperative Adverse Drug Event Surveillance project (2007 through 2009) to estimate the frequency and rates of hospitalization after emergency department visits for adverse drug events in older adults. In addition, the study assessed the contribution of specific medications, including those identified as high-risk or potentially inappropriate by national quality measures.

 

Results showed that based on the 5,077 cases identified in the study sample, the authors projected there were an estimated 99,628 emergency hospitalizations (95% confidence interval [CI], 55,531 to 143,724) for adverse drug events in the U.S. for adults 65 years of age or older each year from 2007 through 2009. Shockingly, nearly half of these hospitalizations were among adults 80 years of age or older. Nearly two thirds of hospitalizations were due to unintentional overdoses. Four medications or medication classes were implicated alone or in combination in 67.0% of hospitalizations: warfarin (33.3%), insulins (13.9%), oral antiplatelet agents (13.3%), and oral hypoglycemic agents (10.7%). High-risk medications were implicated in only 1.2% of hospitalizations.

 

According to the authors, most emergency hospitalizations for recognized adverse drug events in older adults resulted from a few commonly used medications, and relatively few resulted from medications typically designated as high-risk or inappropriate and that improved management of antithrombotic and antidiabetic drugs has the potential to reduce hospitalizations for adverse drug events in older adults.

 

Factors Associated With Treatment Response to Etanercept in Juvenile Idiopathic Arthritis

 

 

Since the introduction of biologic therapies, the pharmacological treatment approach for juvenile idiopathic arthritis (JIA) has changed substantially, with achievement of inactive disease as a realistic goal. As a result, a study published online in the New England Journal of Medicine (6 November 2011) was performed to determine the response to therapy after initiation of etanercept (Enbrel, Pfizer) therapy among patients with JIA and to examine the association between baseline factors and response to etanercept treatment.

 

For the study, data were collected from the Arthritis and Biologicals in Children Register, an ongoing prospective observational study since 1999, which includes all Dutch JIA patients who use biologic agents. All biologically naive patients who started etanercept before October 2009 were included, with follow-up data to January 2011. Among the 262 patients, 185 (71%) were female, 46 (18%) had systemic-onset, and the median age at initiation of etanercept treatment was 12.4 years.

 

The main outcome measures were evaluated 15 months after initiation of treatment and were categorized as 1) excellent response (inactive disease or discontinuation earlier due to disease remission), 2) intermediate response (more than 50% improvement from baseline, but no inactive disease), and 3) poor response (less than 50% improvement from baseline or discontinuation earlier due to ineffectiveness or intolerance).

 

Results showed that at 15 months after treatment initiation, 85 patients (32%) were considered excellent responders; 92 (36%), intermediate responders; and 85 (32%), poor responders. Compared with an intermediate or poor response, an excellent response was associated with lower baseline disability score (range, 0-3 points, with 0 being the best score; fewer disease-modifying antirheumatic drugs (DMARD) (including methotrexate) used before initiating etanercept, and younger age at onset. Compared with an intermediate or excellent response, a poor response was associated with systemic JIA (adjusted OR systemic vs nonsystemic categories, 2.92), and female gender (adjusted OR female vs male, 2.16). Within the first 15 months of etanercept treatment, 119 patients experienced 1 or more infectious, noninfectious, or serious adverse events, including 37 among those with an excellent response, 36 with an intermediate response, and 46 with a poor response. Within the first 15 months of treatment, 61 patients discontinued etanercept treatment, including 4 with an excellent response, 0 with an intermediate response, and 57 with a poor response. In a secondary analysis of 262 patients with a median follow-up of 35.6 months after initiation of etanercept, a range of 37% to 49% of patients reached inactive disease. The mean adherence to etanercept was 49.2 months for patients with an excellent response after 15 months, 47.5 months for patients with an intermediate response, and 17.4 months for patients with a poor response.

 

According to the authors, among patients with JIA who initiated treatment with etanercept, one-third achieved an excellent response, one-third an intermediate response, and one-third a poor response to therapy. Achievement of an excellent response was associated with low baseline disability scores, DMARDs used before initiating etanercept, and younger age at onset of JIA. Achievement of a poor treatment response was associated with systemic JIA and female gender.

 

Relationship of Persistent Symptoms of Anxiety to Morbidity and Mortality Outcomes in Patients with Coronary Heart Disease

 

 

The prevalence of symptoms of anxiety is high in patients with coronary heart disease (CHD), but their effect on cardiac events and mortality has not been well characterized. As a result, a study published in Psychosomatic Medicine (2011;73:803-809), was performed to examine the association of symptoms of persistent anxiety with the development of acute cardiac events in patients with CHD followed over a 2-year period.

 

For the study, of 3,522 enrolled patients with confirmed CHD, data on symptoms of anxiety were available at two time points in 3,048. These patients were then followed for detection of the composite end point of hospitalization for myocardial infarction, unstable or stable angina, other cardiac causes, or all-cause mortality. A composite anxiety symptoms score composed of baseline and 3-month anxiety data, in which the continuous-level scores were used, was tested using Cox proportional hazards regression model. Groups (persistent anxiety [anxiety at both time points] versus nonanxious [no anxiety at either time point] versus not persistently anxious [anxiety only at one time point]) were also compared.

 

Symptoms of persistent anxiety, were associated with shorter time to event. Persistent anxiety remained as an independent predictor of the end point after controlling for multiple variables (persistent anxiety as a summary score (hazard ratio = 1.27) and persistent anxiety as a categorical variable (hazard ratio = 1.52).

 

According to the authors, by measuring anxiety symptoms at more than one time point and controlling for relevant sociodemographic, comorbidity, risk factor, and psychological covariates, it was shown that symptoms of persistent anxiety are a strong, independent predictor of cardiac event–free survival.

TARGET HEALTH excels in Regulatory Affairs and Public Policy issues. Each week we highlight new information in these challenging areas

 

 

FDA Outlines Flexible Approaches for Artificial Pancreas System Clinical Trials, Product Approvals

 

 

People with type 1 diabetes must monitor their blood sugar using a glucose meter throughout the day, calculating how much insulin is needed to lower their blood glucose levels, and administering the necessary dose using a syringe or insulin pump to deliver insulin into subcutaneous tissue. While an artificial pancreas system does not involve synthetic or artificial tissue or organs, it does combine two medical devices, an insulin pump and a continuous glucose monitor (CGM) that receives information on glucose levels from a sensor placed under the patient’s skin. The pump and CGM work together, monitoring the body’s glucose levels and automatically pumping appropriate doses of insulin as determined by a computer algorithm. While not a cure, an artificial pancreas could reduce dangerous high and low blood sugars, providing a better quality of life for those with diabetes and lowering the risk for future diabetes-related complications.

 

The FDA has issued a draft guidance entitled “The Content of Investigational Device Exemption (IDE) and Premarket Approval (PMA) Applications for Artificial Pancreas Device Systems Draft Guidance.” The guidance is designed to help investigators and manufacturers as they develop and seek approval for artificial pancreas device systems to treat type 1 diabetes. To facilitate development of this novel product in an evolving area, the draft guidance provides flexible recommendations for design and testing that meet statutory requirements for safety and effectiveness. For example, the draft guidance provides for flexibility in choice of study endpoints, number of patients to be studied and the length of the clinical trial.

 

According to Jeffrey Shuren, M.D., director of the FDA’s Center for Devices and Radiological Health “The FDA is focused on improving the process for the study and approval of artificial pancreas systems, and developed this guidance to provide maximum flexibility to manufacturers seeking to bring this device to U.S. patients.” Dr. Shuren added that “We understand how this device could change the lives of millions of Americans with diabetes, and we want our safety and effectiveness review to give patients the confidence that the device works.”

 

The guidance recommends a three-phase clinical study progression so that studies may move to an outpatient setting as quickly as possible. To further streamline clinical studies, the guidance suggests ways sponsors may leverage existing safety and effectiveness data for components that may make up an artificial pancreas system, as well as data gathered from clinical studies conducted outside of the U.S. Sponsors also have the choice of showing that the system provides glycemic control as well as standard therapies, or showing that it provides better glycemic control when compared to other therapies. When final, the guidance will help manufacturers and investigators assemble submissions for clinical trials as well as product approval submissions.

Commentary on Avoidable Hospitalizations –
Let’s Pick the Low Hanging Fruit

 

 

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

 

 

As we all know, there is an array of extensive, complex and methodologically diverse (and expensive) efforts supported by an array of public and private sources focused on enhancing healthcare quality and rationalization of costs. Confronting this array of seemingly intractable hurdles, among these an aging population, an obesity epidemic, inefficient data management and system connectivity, as well as a chronically fragmented delivery system. The only certainty about these efforts is that success will be as difficult as it is essential.

 

Given these challenges, and the related slow pace of progress, it was encouraging to review a recent publication that, seemingly, points to some low-hanging fruit in confronting the cost & quality challenges.

 

Daniel Budnitz and colleagues (NEJM 365;21 November 24th, 2011 Page 2002) recently reported on an investigation of emergency hospitalizations in the elderly, specifically hospitalizations required as a consequence of adverse events related to medications. They reported several interesting, (perhaps unexpected) and encouraging, findings.

 

It was likely unsurprisingly but still potentially reassuring that the large majority of these emergency admissions was a consequence of a small number of medicines used in limited therapeutic categories; including warfarin, insulin preparations, oral anti-platelet agents and oral hypoglycemic agents. In most cases, the problems requiring admission resulted from hemorrhage and hypoglycemia, e.g., excessive effects based upon their desired actions. As the authors point out, more attentive anticoagulant management (for warfarin), rigorous patient selection and counseling (for oral anti-platelet agents), and potential changes in the recommended goals for glucose levels in diabetes management (for insulin preparations and oral anti-hypoglycemic agents), especially in the “older- elderly” (>80), have the potential to ameliorate the complications of therapy. Perhaps unexpectedly, the incidence of hospitalization secondary to frankly inappropriate prescribing was much lower than for the medicines above, which as noted were likely largely used for appropriate indications but showed excessive therapeutic effects.

 

If the authors’ estimate of nearly 100,000/year of these drug related emergency hospitalizations is accurate, the potential savings in both patient morbidity and costly hospitalizations are huge. Thus we have, at least in theory, the best of all possible worlds; specifically, the chance to improve quality and save money without denying needed services to anyone. The obvious conclusion: focused attention to improving the medication management of patients requiring anticoagulation and diabetes management, something we should be doing anyway, can diminish morbidity and lower spending with no commensurate costs in denying access to services or limiting physician or patient autonomy.

 

In sum, everybody wins…an unusual healthcare outcome.