DIA Annual Meeting – See Us at Booth 913


We hope to see you in Chicago and join us on our couches.

A reminder that Dr. Jules T. Mitchel will be chairing a Content Hub presentation / conversation which will take place at the DIA Annual Meeting in Chicago. Please join us at 4pm on Tuesday June 20, 2017 at the S400 Concourse. The topic is:


How eSource Solutions are Impacting Clinical Research Sites, Patients, Regulators and Drug and Device Companies


Co-presenting will be our colleagues and friends:


Jonathan Helfgott, MS, who is currently the Coordinator of the Regulatory Science Graduate Program at Johns Hopkins University, and previously the Associate Director for Risk Science at FDA CDER OSI and the main author of FDA’s eSource Guidance, and;


Mitchell D. Efros MD FACS, CEO of Verified Clinical Trials


The following is an outline of the presentation and we look forward to seeing you there:


In the not too distant future, we, as an industry will execute, manage and monitor clinical trials the same way we execute, manage and monitor banking transactions online, quickly and without the need to maintain paper records. However, as we bring new and innovative technology solutions to the market, we must assess and address the concerns of all the stakeholders within the clinical trial enterprise. We need to assure patients, clinical research sites, pharmaceutical and device companies, as well as regulators, that there will be improved efficiencies, improved data quality and integrity, improved patient safety, reduced fraud and an overall better experience during the clinical trial process. Topics to be addressed include clinical site acceptance, regulatory concerns, software validation, risk assessments, change management within companies, and a comprehensive assessment of the risks and rewards.


For more information about Target Health contact Warren Pearlson (212-681-2100 ext. 165). For additional information about software tools for paperless clinical trials, please also feel free to contact Dr. Jules T. Mitchel. The Target Health software tools are designed to partner with both CROs and Sponsors. Please visit the Target Health Website.


Joyce Hays, Founder and Editor in Chief of On Target

Jules Mitchel, Editor



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How Much of Biology/Physiology 101 Do You Remember?

Basic overview of energy and human life. Graphic credit: Mikael Haggstrom, Public Domain, license.File:Pikilia.JPG, Wikipedia Commons


Physiology is the study of the mechanical, physical, and biochemical processes of living organisms function as a whole. Physiology is also the study the interaction of how, for example, the nervous, immune, endocrine, respiratory, and circulatory systems, function and interplay. The study of these systems is shared with such medically oriented disciplines as neurology and immunology. The theme of “structure to function“ is central to biology. Physiological studies have traditionally been divided into plant physiology and animal physiology, but some principles of physiology are universal, no matter what particular organism is being studied. For example, what is learned about the physiology of yeast cells can also apply to human cells. The field of animal physiology extends the tools and methods of human physiology to non-human species. Plant physiology borrows techniques from both research fields.


Q1. Name of the procedure that makes a hole in the skull?

Q2. What is the name of a foreign substance that stimulates an immune response (ex: bacteria, viruses, microorganisms)

Q3. Differentiate the T cells and the B cells

Q4. What are the six organs, listed sequentially through which food passes through the body?

Q5. Which philosopher influenced modern medicine with his view that, the mind and body operate according to separate principles

Q6. Name the term used, when the activation of the sympathetic division of the autonomic nervous system produces a reaction. What is this response called?

Q7. What is the name of the white blood cells that are involved in the immune response?

Q8. Name three of the 6 major neurotransmitters

Q9. What is prednisolone?

Q10. What is the major hormone produced by the adrenal cortex, secreted by the adrenal gland, in response to stimulation or stress. This hormone has anti-inflammatory activity.



1) Trephination; 2) An antigen; 3) T cells directly attack antigens, B cells attack antigen by secreting antibodies; 4) oral cavity, pharynx, esophagus, stomach, small intestine, large intestine; 5) Rene Descartes; 6) Often described as the fight or flight response; 7) lymphocytes;

8a) Acetylcholine – important for learning, memory, and muscle memory

8b) Gamma-aminobutyric acid (GABA) – linked to the experience of anxiety, alcohol abuse, seizure and sleep disorders

8c) Serotonin – influences mood and regulates food intake

8d) Dopamine – important to frontal lobe activity. Is involved in movement, thought processes, emotions, and feelings of reward and pleasure 

8e) Norepinephrine – maintains alertness and wakefulness

8f) Endorphins – regulate firing of pain neurons and respond to feelings of pleasure

9) Synthetic steroid; 10) Cortisol

Medicine and the Philosophy of Rene Descartes; Cogito ergo sum

Rene Descartes at work Credit: Public Domain, Wikipedia Commons


The French philosopher and mathematician Rene Descartes (1596-1650) gave a high priority to medicine and dedicated a great deal of his life to medical studies. Nevertheless, his relation to medicine has always been debated. A number of recent works have contributed to reassessing the earlier critique which nearly wrote him out from medical history. The recent biographical dismissal of a number of earlier allegations and the recent interpretations of the medical contents of his collected writings ought to result in Descartes’ reinstatement in medical history.


Painting of Rene Descartes by Frans Hals – Credit: After Frans Hals – Andre Hatala [e.a.] (1997) De eeuw van Rembrandt, Bruxelles: Credit communal de Belgique, ISBN 2-908388-32-4., Public Domain; Wikipedia Commons


His novel anti-Aristotelian methodology had a crucial influence on the medicine of the subsequent decades. Also, his early defense of Harvey’s theory of blood circulation had great influence. Especially his thoughts about a mechanical physiology by means of which the functions of the body could be explained without involvement of “occult faculties“ influenced that time. His empirical mistakes, including the central role which he ascribed to the corpus pineale, are offset by his brilliant thoughts about the function and importance of the brain. Although he did not make any really new empirical discoveries within medicine, he advanced a number of concrete ideas which later lead to actual discoveries such as visual accommodation, the reflex concept and the reciprocal innervations of antagonistic muscles. Descartes’ psychosomatic view of the importance of the interplay between sensations, “the passions of the soul“, and the free will in the preservation of health shows in addition that his fundamental soul-body dualism was far more nuanced than is often claimed. Descartes developed a system of dualism which distinguishes between the “mind,“ whose essence is thinking, and “matter,“ whose essence is extended into space; with more flexibility for definition. This dualism influenced his mechanical interpretation of nature and therefore of the human body. He believed that the laws of physics and mathematics explain human physiology.


According to One Hundred Books Famous in MedicineDe homine, “is the first work in the history of science and medicine to construct a unified system of human physiology that presents man as a purely material and mechanical being: man as machine de terre.“ This concept helped free the study of physiology from the constraints of religion and culture. De homine is an important early textbook of physiology, but empirically flawed because Descartes’ practical knowledge of his subject was inadequate. With extraordinary courage, Descartes refused to accept the authority of previous philosophers. He frequently set his views apart from those of his predecessors. In the opening section of the Passions of the Soul, a treatise on the early modern version of what are now commonly called emotions, Descartes goes so far as to assert that he will write on this topic “as if no one had written on these matters before“. His best known philosophical statement is “Cogito ergo sum“ The thrilling nature of this stance is not only that Descartes separated the study of man (philosophy and medicine) from religious dogma, but he created new pathways of medical and scientific inquiry, deviating from nearly two thousand years of unquestioned adherence to the medical knowledge of Hippocrates (360 BCE) and Galen (129 CE  200 CE).


Human ideas die hard. The history of science and medicine gives clear proof of this. Ideas change fast in the 21st Century, therefore, it’s hard to believe that the approach to medicine barely changed over approximately 2,000 years and that the teachings of Hippocrates and Galen lasted right up to the 17th Century. At this point, the great genius of Rene Descartes asserted, “No, I am different.“ His creativity literally changed the history of human thought. Descartes originally planned to publish De homine in 1633, but hearing of Galileo’s condemnation by the Church, he became concerned for his own safety and refused to have it printed. Consequently, the first edition of this work appeared 12 years after Descartes’ death. The French edition, L’homme, also includes la formation du foetus which explains reproductive generation in physiological terms. Sources: ncbi.nlm.nih.gov/pubmed; Wikipedia; virginia.edu/treasures/rene-descartes-1596-1650/



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Overall Survival Results of a Trial Assessing Patient-Reported Outcomes for Symptom Monitoring During Routine Cancer Treatment


Symptoms are common among patients receiving treatment for advanced cancers, yet are undetected by clinicians up to half the time There is growing interest in integrating electronic patient-reported outcomes (PROs) into routine oncology practice for symptom monitoring, but evidence demonstrating clinical benefit has been limited. As a result, a study published online in JAMA (4 June 2017) assessed overall survival associated with electronic patient-reported symptom monitoring vs usual care based on follow-up from a randomized clinical trial.


For the study, consecutive patients initiating routine chemotherapy for metastatic solid tumors at Memorial Sloan Kettering Cancer Center in New York between September 2007 and January 2011 were invited to participate in a randomized clinical trial. Participants were randomly assigned either to the usual care group or to the PRO group, in which patients provided self-report of 12 common symptoms from the National Cancer Institute’s Common Terminology Criteria for Adverse Events at and between visits via a web-based PRO questionnaire platform. Participation was continuous until cessation of cancer treatment, voluntary withdrawal from the trial, transition to hospice care, or death. When the PRO group participants reported a severe or worsening symptom, an email alert was triggered to a clinical nurse responsible for the care of that patient. A report profiling each participant’s symptom burden history was generated at clinic visits for the treating oncologist. The usual care group received the standard procedure for monitoring symptoms in oncology practice: symptoms were discussed during clinical encounters, and patients could contact the office by telephone between visits for concerning symptoms. The protocol-specified primary outcome was change in health-related quality of life at 6 months compared with enrollment.


Results showed that of 766 patients randomized, the median age was 61 years (range, 26-91), 86% were white, 58% women, 22% had less than a high school education, and 30% were computer inexperienced. Overall survival was assessed in June 2016 after 517 of 766 participants (67%) had died, at which time the median follow-up was 7 years. Median overall survival was 31.2 months in the PRO group and 26.0 months in the usual care group (difference, 5 months; P?=?0.03). In the multivariable model, results remained statistically significant with a hazard ratio of 0.83; P?=?0.04).


According to the authors, integration of PROs into the routine care of patients with metastatic cancer was associated with increased survival compared with usual care. One potential mechanism of action is early responsiveness to patient symptoms preventing adverse downstream consequences. Nurses responded to symptom alerts 77% of the time with discrete clinical interventions including calls to provide symptom management counseling, supportive medications, chemotherapy dose modifications, and referrals. Another potential mechanism is that patients in the intervention group were able to tolerate continuation of chemotherapy longer than usual care (mean, 8.2 months in the PRO group vs 6.3 months in the usual care group; difference, 1.9 months; P?=?0.002).


The authors concluded that electronic patient-reported symptom monitoring may be considered for implementation as a part of high-quality cancer care.


Neuroimaging Technique May Help Predict Autism Among High-Risk Infants


Autism affects roughly 1 out of every 68 children in the United States, and siblings of children diagnosed with autism are at higher risk of developing the disorder. Although early diagnosis and intervention can help improve outcomes, there currently is no method to diagnose the disease before children show symptoms. Previous findings suggest that brain-related changes occur in autism before behavioral symptoms emerge.


According to a study published online Science Translational Medicine (7 June 2017), functional connectivity magnetic resonance imaging (fcMRI) may predict which high-risk, 6-month old infants will develop autism spectrum disorder by age 2 years. The study focused on the brain’s functional connectivity — how regions of the brain work together during different tasks and during rest. Using fcMRI, the authors scanned 59 high-risk, 6-month-old infants while they slept naturally. The children were deemed high-risk because they had older siblings with autism. At age 2 years, 11 of the 59 infants in this group were diagnosed with autism.


The authors used a computer-based technology called machine learning, which trains itself to look for differences that can separate the neuroimaging results into two groups — autism or non-autism — and predict future diagnoses. One analysis predicted each infant’s future diagnosis by using the other 58 infants’ data to train the computer program. This method identified 82% of the infants who would go on to have autism (9 out of 11), and it correctly identified all of the infants who did not develop autism. In another analysis that tested how well the results could apply to other cases, the computer program predicted diagnoses for groups of 10 infants, at an accuracy rate of 93%.


Overall, the team found 974 functional connections in the brains of 6-month-olds that were associated with autism-related behaviors. The authors proposed that a single neuroimaging scan may accurately predict autism among high-risk infants, but caution that the findings need to be replicated in a larger group.


FDA Requests Removal of Opana ER for Risks Related to Abuse


The FDA has requested that Endo Pharmaceuticals remove its opioid pain medication, reformulated Opana ER (oxymorphone hydrochloride), from the market. After careful consideration, the agency is seeking removal based on its concern that the benefits of the drug may no longer outweigh its risks. This is the first time the agency has taken steps to remove a currently marketed opioid pain medication from sale due to the public health consequences of abuse.


The FDA’s decision is based on a review of all available post-marketing data, which demonstrated a significant shift in the route of abuse of Opana ER from nasal to injection following the product’s reformulation. Injection abuse of reformulated Opana ER has been associated with a serious outbreak of HIV and hepatitis C, as well as cases of a serious blood disorder (thrombotic microangiopathy). This decision follows a March 2017 FDA advisory committee meeting where a group of independent experts voted 18-8 that the benefits of reformulated Opana ER no longer outweigh its risks.


Opana ER was first approved in 2006 for the management of moderate-to-severe pain when a continuous, around-the-clock opioid analgesic is needed for an extended period of time. In 2012, Endo replaced the original formulation of Opana ER with a new formulation intended to make the drug resistant to physical and chemical manipulation for abuse by snorting or injecting. While the product met the regulatory standards for approval, the FDA determined that the data did not show that the reformulation could be expected to meaningfully reduce abuse and declined the company’s request to include labeling describing potentially abuse-deterrent properties for Opana ER. Now, with more information about the risks of the reformulated product, the agency is taking steps to remove the reformulated Opana ER from the market.


The FDA has requested that the company voluntarily remove reformulated Opana ER from the market. Should the company choose not to remove the product, the agency intends to take steps to formally require its removal by withdrawing approval. In the interim, the FDA is making health care professionals and others aware of the particularly serious risks associated with the abuse of this product. The FDA will continue to examine the risk-benefit profile of all approved opioid analgesic products and take further actions as appropriate as a part of our response to this public health crisis.


Practically Perfect Veggie Burger

After much trial and error, I want to share with you, a delicious veggie burger recipe.  By adding one fresh beet, health, flavor and color are well dispensed.  Tempeh is another must; it adds wonderful texture, as well as flavor.  Never have burgers disappeared so fast over one weekend.  These burgers were served over tri-color farfalla with a mushroom gravy.  What looks like mashed potatoes, to the right, is actually an easy recipe that I concocted about two years ago: steamed cauliflower mashed with chopped scallions and truffle oil.  ©Joyce Hays, Target Health Inc.



1 medium beet or two small beets: wash, peel, dice or slice

4 ounces extra-firm tofu, drained

1/2 cup Coconut oil or extra virgin olive oil

1/2 pound cremini, button or baby bella mushrooms, trimmed and sliced

Pinch kosher salt (or to your taste)

Pinch black pepper (or to your taste)

2 Pinches chili flakes (or to your taste)

1 (15-ounce) can kidney beans, drained

3/4 cup toasted (unsalted) cashews

1/3 cup panko

2 ounces Queso blanco cheese, crumbled or grated (about 1/2 cup)

2 large eggs

2 Tablespoons Kraft mayonnaise

2 scallions, sliced

4 garlic cloves, finely chopped, plus 1 more squeezed

3/4 teaspoon sweet smoked paprika

4 ounces tempeh, crumbled

1/2 cup cooked brown rice



1. Heat oven to 425 degrees.

2.  In a medium to large bowl, put the oil, salt, pepper, chili flakes, 1 squeezed garlic clove and mix together.  Set aside

3. Slice tofu into 1/4-inch-thick slabs and pat dry with paper towel. Then put into the bowl with oil and seasoning.

4. Line 2 rimmed baking sheets with parchment and with a slotted spoon, remove the tofu and place on one side of the baking sheet.

5. Clean mushrooms, then slice them and put into the bowl with oil.

6.With a slotted spoon, remove mushrooms and put them on the other half of the baking sheet.


Going into the oven.  ©Joyce Hays, Target Health Inc.


7. Toss the beans in the bowl of oil and seasonings, then with slotted spoon, remove the beans and put on one side of the second rimmed baking sheet.

8. Put the sliced or diced beet into the bowl of seasoned oil, then remove the beets and put on the other half of the rimmed baking sheet.


Going into the oven.  ©Joyce Hays, Target Health Inc.


9. Put both baking sheets into the oven. Roast the beans and beets until the beans start splitting. By this time, the beets should be tender. This should take about 15 minutes. Roast  the baking sheet with mushrooms and tofu until the tofu is golden.  This should take about 25 minutes. Remove sheets from oven: 1 after 15 minutes, the other after 25 minutes; then let everything cool.

10. Meanwhile, put nuts in food processor.  Pulse until coarsely ground. Next add the beans and beets and pulse.  Next the mushrooms and tofu and pulse.  At any time, when the food processor is filled, and contents have been pulsed, take a spatula and scrape all contents into a large mixing bowl.

11. Next, add to food processor the panko, cheese, eggs, mayonnaise, scallion, 4 garlic cloves, paprika, chili flakes. Pulse until ingredients are just combined. Pulse in the tempeh and rice but do not over-process. You want small chunks, not a smooth mixture. You do NOT want a smooth paste, because you want the burgers to have texture to chew down on.


One of many batches in food processor.  ©Joyce Hays, Target Health Inc.


Another batch getting pulsed.  ©Joyce Hays, Target Health Inc.


This recipe doesn’t work without a food processor.  ©Joyce Hays, Target Health Inc.


Nearly done.  ©Joyce Hays, Target Health Inc.


12. After everything has been pulsed, scrape it all into that large mixing bowl and chill in fridge, overnight.  The burgers will cook better the next day, if you have chilled them overnight.


Be sure to mix everything together very well.  Do not use electric beaters for this step of the recipe.  ©Joyce Hays, Target Health Inc.


13. When you are ready to make the burgers, divide mixture into 6 equal portions which yields large burgers.  I’ve made these many times and now prefer a slightly smaller size.  You decide the size you want and form each portion into a patty about 1 inch thick. Return to the fridge until just before grilling. They cook better when they start out cold.  I have never baked the burgers, but am betting they would be very good; also tasty, if grilled.

14. Cook the burgers in a skillet, over a high flame, until they are charred on both sides.  Then lower the flame and cook for about 5 to 7 minutes, over low heat.  You want these burgers to be crispy on the outside.


Before chilling overnight in fridge, the mixture should look like this, or close to it.  ©Joyce Hays, Target Health Inc.


Cooking the burgers – you want them to be crispy on the outside.  ©Joyce Hays, Target Health Inc.


15 That’s it!  Use your imagination and serve these veggie burgers any way you want.  In a bun or without.  With ketchup or with your own sauce.  For one meal, I made a mushroom gravy.  On another day, I made a yogurt garlic sauce, and served the burgers with fresh sliced tomatoes and avocados.  I haven’t tried a mustard sauce, but am thinking about doing that.


Out of the pan and onto the table.  ©Joyce Hays, Target Health Inc.


You could add a bun, onion rings, ketchup, etc.  Your choice.  ©Joyce Hays, Target Health Inc.


A delicious dinner: burgers, farfalle, mushroom gravy. mashed cauliflower with truffle oil and a crunchy garden salad.  Not to mention a delicious Shiraz.  ©Joyce Hays, Target Health Inc.


Definitely worth snacking on.  ©Joyce Hays, Target Health Inc.


We’re drinking another Henschke (Australia) Shiraz, which went well with the burgers.  ©Joyce Hays, Target Health Inc.



From Our Table to Yours

Bon Appetit!