Disruptive Innovation Meeting – September 11-12, 2014, Boston

 

For those of us committed to change, not for its own sake but to make what we do better and more effective, we want to highlight one of the best conferences in the industry. Our friends at The Conference Forum will be running the 4th annual meeting of Dpharm: Disruptive Innovations to Advance Clinical Trials. This most exciting conference will be held September 11-12, 2014, at The Fairmont Copley Plaza, Boston, MA. Make plans to participate as you will not be disappointed. Check out the website or just send us a note and we will connect you to the organizers (http://theconferenceforum.org/conferences/disruptive-innovations/overview/). We are also pleased to announce that Dr. Jules T. Mitchel, President of Target Health is on the Advisory Board of the conference.  

 

The conference is designed for leaders in clinical research who are open to new and alternative approaches to making clinical development far more productive and sustainable. The conference brings together a speaking faculty of a diverse community of leading thinkers and practitioners of clinical trials who are experimenting with breakthrough models and approaches. Their case studies will demonstrate examples of transformative and disruptive approaches to advancing clinical trials.

 

ON TARGET is the newsletter of Target Health Inc., a NYC-based contract research organization (CRO), providing strategic planning, regulatory affairs, clinical research, data management, biostatistics, medical writing and software services, including the paperless clinical trial, to the pharmaceutical and device industries.

 

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.

 

Joyce Hays, Founder and Chief Editor of On Target

Jules Mitchel, Editor

Anger Is Fast Trigger for Heart Attack or Stroke

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A stroke, or cerebrovascular accident (CVA), is the rapid loss of brain function(s) due to disturbance in the blood supply to the brain. This can be due to ischemia (lack of blood flow) caused by blockage (thrombosis, arterial embolism), or a 1) ___. As a result, the affected area of the brain cannot function, which might result in an inability to move one or more limbs on one side of the body, inability to understand or formulate speech, or an inability to see one side of the visual field. A stroke is a medical emergency and can cause permanent neurological damage, complications, and death. Risk factors for stroke include old age, hypertension (high blood pressure), previous stroke or transient ischemic attack (TIA), diabetes, high cholesterol, cigarette smoking and atrial fibrillation. High blood pressure is the most important modifiable risk factor of stroke. It is the second leading cause of 2) ___ worldwide.

 

Cardiovascular disease (also called heart disease) is a class of diseases that involve the heart, the blood vessels (arteries, capillaries, and veins) or both. Cardiovascular disease refers to any disease that affects the cardiovascular system, principally cardiac disease, vascular diseases of the brain and kidney, and peripheral arterial disease. The causes of cardiovascular disease are diverse but atherosclerosis and/or hypertension are the most common. In addition, with aging come a number of physiological and morphological changes that alter cardiovascular function and lead to increased risk of cardiovascular disease, even in healthy asymptomatic individuals. Cardiovascular disease is the leading cause of deaths worldwide, though, since the 1970s, cardiovascular 3) ___ rates have declined in many high-income countries. At the same time, cardiovascular deaths and disease have increased at a fast rate in low- and middle-income countries. Although cardiovascular disease usually affects older adults, the antecedents of cardiovascular disease, notably atherosclerosis, begin in early life, making primary prevention efforts necessary from childhood. There is therefore increased emphasis on preventing atherosclerosis by modifying risk factors, such as healthy eating, exercise, and avoidance of smoking tobacco. Some of these risk factors, such as age, gender or family history, are immutable; however, many important cardiovascular risk factors are modifiable by lifestyle change, social change, drug treatment and prevention of Serrano’s Cardiac Triad: hypertension, hyperlipidemia, and 4) ___.

 

Interesting research is being done on the relationship between a lifestyle change of anger management and cardiovascular event or stroke. A flash of anger may send the body down a path ending in a heart attack or stroke, a systemic review showed. Note that the magnitude of increased risks were higher for individuals who had a greater cardiovascular risk initially. Although relatively few studies have explored the link between short bouts of 5) ___ and cardiovascular events in the hours immediately following the outburst, the evidence is consistent in showing a direct relationship, according to Murray Mittleman, Dr PH, of the Harvard School of Public Health, and colleagues. But it’s not clear how substantial the risk is, the authors reported online in the European Heart Journal. “The relative risks estimated in this meta-analysis indicate that there is a higher risk of cardiovascular 6) ___ after outbursts of anger among individuals at risk of a cardiovascular event, but because each episode may be infrequent and the effect period is transient, the net absolute impact on disease burden is extremely low,“ they wrote. “However, with increasing frequency of anger episodes, these transient effects may accumulate, leading to a larger clinical impact.“

 

Several smaller studies have examined the link between anger and cardiovascular health, but Mittleman and colleagues set out to explore the consistency of the association. A review of the literature turned up nine independent case-crossover studies conducted in the U.S., Sweden, England, Israel, and the Netherlands. Outcomes included myocardial 7) ___, acute coronary syndromes, stroke, and ventricular arrhythmia in the 2 hours following angry outbursts. In pooled results of four of the studies, the risk of MI or acute coronary syndrome was 4.74-fold higher in the hours after an outburst. In pooled results of two studies, the risk of ischemic stroke was not significantly elevated. One study evaluated intracranial hemorrhage and showed that the risk was higher in the hour after a bout of anger. Two studies had ventricular arrhythmia in patients with implantable cardioverter-defibrillators as an outcome, although the results could not be combined because of differences in the measurement of anger, study design, and hazard periods. One showed that risk was significantly higher in the 15 minutes after an outburst and the other showed that the 8) ___ was higher in the hour after the angry episode. Mittleman and colleagues noted that magnitude of increased risks was higher for individuals who had a greater cardiovascular risk initially. For MI/acute coronary syndrome, for example, “the absolute impact of one episode of anger per month is only one excess cardiovascular event per 10,000 individuals per year at low (5%) 10-year cardiovascular risk and four excess cardiovascular events per 10,000 individuals per year at high (20%) 10-year 9) ___ risk.“ In an accompanying editorial, Suzanne Arnold, MD, of Saint Luke’s Mid America Heart Institute in Kansas City, Mo., and colleagues discussed some of the potential mechanisms tying anger to cardiovascular events and stated that “Mediated through increases in circulating catecholamines, increased myocardial oxygen demand, coronary vasospasm, and increased platelet aggregability, anger can cause transient ischemia, disruption of vulnerable plaques, and increased thrombotic potential, and that these changes can then result in myocardial or cerebral ischemia or malignant arrhythmias.“ They authors also pointed out that the review was limited by the small number of available studies and the significant heterogeneity between them, but said that the findings highlight the consistency of results linking acute anger and increased cardiovascular risk. “However, how to move forward in reducing the burden of these risk factors in patients and, hopefully, its impact on cardiovascular health is still in question,“ they wrote. “Given the lessons we have learned from trying to treat depression after MI, treating anger in isolation is unlikely to be impactful. Instead, a broader and more comprehensive approach to treating acute and chronic mental stress, and its associated psychological stressors, is likely to be needed to heal a hostile heart.“ Mittleman and colleagues noted in their paper that studies of 10) ___ — including beta-blockers and selective serotonin reuptake inhibitors — have not shown substantial benefits, and said that psychological interventions might help.

 

In an email to MedPage Today, Redford Williams, MD, of Duke University, said that beta-blockers could ease some of the negative consequences of angry outbursts but that their use would be limited by side effects. He agreed the 11) ___ interventions might be worthwhile. “Behavioral interventions that train folks to reduce angry outbursts and/or the accompanying physiological arousal could be an effective means of reducing the health damage associated with angry outbursts,“ he said, backing that up with three prior studies. The first showed that a group-based psychosocial intervention designed to reduce stress, cut mortality among women with coronary heart disease. The second demonstrated that cognitive behavioral therapy with a focus on stress management lowered the risk of recurrent cardiovascular events in men and women with established coronary heart disease. And the final paper cited by Williams showed that a psychosocial skills training workshop reduced anger 12) ___ and the size of the increases in blood pressure and heart rate that accompanied the recall of situations that made men who had undergone CABG, angry.

 

Sources:

1.    American Heart Association: Trait Antagonism and the Progression of Arterial Thickening

2.    European Heart Journal: Mostofsky E, et al “Outbursts of anger as a trigger of acute cardiovascular events: a systematic review and meta-analysis“ Eur Heart J 2014; DOI: 10.1093/eurheartj/ehu033.

3.    European Heart Journal: Arnold S, et al “The hostile heart: anger as a trigger for acute cardiovascular events“ Eur Heart J 2014; DOI: 10.1093/eurheartj/ehu097;

4.    MedPageToday.com

 

ANSWERS: 1) hemorrhage; 2) death; 3)Mortality; 4) diabetes; 5) anger; 6) events; 7) infarction; 8) risk; 9) cardiovascular; 10) medications; 11) psychological; 12) levels

Thomas Willis MD (1621-1625), Father of Neuroscience

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Thomas Willis (27 January 1621 – 11 November 1675) was an English doctor who played an important part in the history of anatomy, neurology and psychiatry. He was a founding member of the Royal Society and is often called the father of neuroscience. Willis was born on his parents’ farm in Great Bedwyn, Wiltshire, where his father held the stewardship of the Manor. He was a kinsman of the Willys baronets of Fen Ditton, Cambridgeshire. At Oxford University he did a Bachelors degree, and Masters degree. Once qualified with a B. Med. in 1646, he began as an active physician by regularly attending the market at Abingdon.

 

Willis obtained his medical degree from Christ Church, Oxford. While at Oxford, he became Sedleian Professor of Natural History in 1660, and retained that position until his death. He did much experimental work with his associate Richard Lower. He performed injection experiments on cadavers and noted that if he injected the carotid artery on one side, the dye solution would come forth from the carotid on the opposite side.

 

He maintained an Anglican position; an Anglican congregation met at his lodgings in the 1650s, including John Fell, John Dolben, and Richard Allestree. Fell’s father Samuel Fell had been expelled as Dean of Christ Church, in 1647; Willis married Samuel Fell’s daughter Mary, and brother-in-law John Fell would later be his biographer. He employed Robert Hooke as an assistant, in the period 1656-58; this probably was another Fell family connection, since Samuel Fell knew Hooke’s father in Freshwater, Isle of Wight.

 

In 1664 Willis published his monumental work Cerebri Anatome, the most complete and accurate account of the nervous system that had hitherto appeared. In it he contributed the term “neurology“ to medicine, a word derived from the Greek, meaning “sinew,“ “tendon,“ or “bowstring.“ The word was translated and introduced into the English language in 1681 in Samuel Pordage’s translation of Willis’ work. Cerebri Anatome contains a classification of the cerebral nerves, the first description of the eleventh nerve, and a description of the hexagonal network of arteries at the base of the brain that we know as the circle of Willis. Although others had described the circle before Willis, he was the first to grasp its physiological and pathological significance. He records the clinical histories of two patients in whom he suggests that the anatomic configuration of the arteries at the base of the brain could prevent apoplexy. The book was illustrated by Christopher Wren, an associate of Willis at Oxford, later to become England’s leading architect and designer of St Paul’s Cathedral, numerous other English churches, and many historic secular buildings.

 

Willis moved to London in 1666 where he continued his careful clinical observations and made a number of other important contributions. He was the first to recognize that lesions in the region of the internal capsule will produce hemiplegia. He was the first (after the ancient Greeks and Romans) to notice the characteristic sweetish taste of diabetic urine. He described myasthenia gravis. He gave the first account of epidemic typhoid fever and typhus. He was the first to describe and name puerperal fever. He described the phenomenon of Willis’ paracusis: a deaf person who can hear only in the presence of noise.

 

One of several Oxford cliques of those interested in science grew up around Willis and Christ Church. Besides Hooke, others in the group were Nathaniel Hodges, John Locke, Richard Lower, Henry Stubbe and John Ward. (Locke went on to study with Thomas Sydenham, who would become Willis’s leading rival, and who both politically and medically held some incompatible views.) In the broader Oxford scene, he was a colleague in the “Oxford Club“ of experimentalists with Ralph Bathurst, Robert Boyle, William Petty, John Wilkins and Christopher Wren. Willis was on close terms with Wren’s sister Susan Holder, skilled in the healing of wounds.

 

In 1656 and 1659, Willis published two significant medical works, De Fermentatione and De Febribus. These were followed by the 1664 volume on the brain, which was a record of collaborative experimental work. From 1660 until his death, he was Sedleian Professor of Natural Philosophy at Oxford.

 

At the time of the formation of the Royal Society of London, he was on the 1660 list of priority candidates, and became a Fellow in 1661. Henry Stubbe became a polemical opponent of the Society, and used his knowledge of Willis’s earlier work before 1660 to belittle some of the claims made by its proponents. Willis later worked as a physician in Westminster, London, this coming about after he treated Gilbert Sheldon in 1666. He had a successful medical practice, in which he applied both his understanding of anatomy and known remedies, attempting to integrate the two; he mixed both iatrochemical and mechanical views. Willis combined the physician’s expert anatomical sophistication with the fluent use of an interpretive apparatus that see-sawed between novelty and tradition, Galenism and Gassendist atomism, iatrochemistry and mechanism. Among his patients was the philosopher Anne Conway, whom he had intimate relations with, but although he was consulted, Willis failed to relieve her headaches.

 

Willis is mentioned in John Aubrey’s Brief Lives; their families became linked generations later through the marriage of Aubrey’s distant cousin Sir John Aubrey, 6th Baronet of Llantrithyd to Martha Catherine Carter, the grand-niece of Sir William Willys, 6th Baronet of Fen Ditton.

 

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Frontispiece to Thomas Willis’ 1663 book “Diatribae duae medico-philosophicae – quarum prior agit de fermentatione“, engraved and published by Gerbrandus Schagen in Amsterdam

 

His anatomy of the brain and nerves, as described in his Cerebri anatome of 1664, is minute and elaborate. This work coined the term neurology, and was not the result of his own personal and unaided exertions; he acknowledged his debt to Christopher Wren, who provided drawings, Thomas Millington, and his fellow anatomist Richard Lower. It abounds in new information, and presents an enormous contrast with the vaguer efforts of his predecessors. In 1667 he published Pathologicae cerebri, et nervosi generis specimen, an important work on the pathology and neurophysiology of the brain. In it he developed a new theory of the cause of epilepsy and other convulsive diseases, and contributed to the development of psychiatry. In 1672 he published the earliest English work on medical psychology, “Two Discourses concerning The Soul of Brutes, Which is that of the Vital and Sensitive of Man“. Willis could be seen as an early pioneer of the mind-brain supervenience claim, prominent in present day neuropsychiatry and philosophy of mind. Unfortunately, his enlightenment did not affect his treatment of patients, advocating in some cases to hit the patient over the head with sticks.

 

Willis was the first to number the cranial nerves in the order in which they are now usually enumerated by anatomists. He noted the parallel lines of the mesolobe (corpus callosum), afterwards minutely described by F?lix Vicq-d’Azyr. He seems to have recognized the communication of the convoluted surface of the brain and that between the lateral cavities beneath the fornix. He described the corpora striata and optic thalami; the four orbicular eminences, with the bridge, which he first named annular protuberance; and the white mammillary eminences, behind the infundibulum. In the cerebellum he remarks about the arborescent arrangement of the white and grey matter, and gives a good account of the internal carotids, and the communications which they make with the branches of the basilar artery.

 

He coined the term mellitus in diabetes mellitus. An old name for the condition is “Willis’s disease“. He observed what had been known for many centuries elsewhere, that the urine is sweet in patients (glycosuria). His observations on diabetes formed a chapter of Pharmaceutice rationalis (1674). Further research came from Johann Conrad Brunner, who had met Willis in London.

 

Willis’s work gained currency in France through the writings of Daniel Duncan. The philosopher Richard Cumberland quickly applied the findings on brain anatomy to argue a case against Thomas Hobbes’s view of the primacy of the passions.

Nations Commit to Accelerating Progress Against Infectious Disease Threats

 

The following shows how with the right leadership and resources, a lot of good can happen.

 

According to Health and Human Services (HHS), the US has joined 26 countries, the World Health Organization (WHO), the Food and Agriculture Organization (FAO), and the World Organization for Animal Health (OIE), to accelerate progress toward a world safe and secure from the threat of infectious disease, and committing to the goals of the Global Health Security Agenda.

 

Over the next five years the US plans to work with at least 30 partner countries (containing at least 4 billion people) to prevent, detect and effectively respond to infectious disease threats, whether naturally occurring or caused by accidental or intentional releases of dangerous pathogens. The recent outbreaks of H7N9 influenza and Middle East Respiratory Syndrome are reminders of the need to step up our efforts as a global community.

 

Later this year, the White House will host an event bringing together nations who are committed to protecting the world from infectious disease threats to review progress and chart the way forward on building a global system for preventing, detecting, and responding to such threats. Last year the Centers for Disease Control and Prevention (CDC) conducted two global health security demonstration projects in partnership with Vietnam and Uganda to strengthen laboratory systems, develop strong public health emergency operations centers, and create real-time data sharing in health emergencies. CDC is committed to replicate the successes in these two projects in ten additional countries this year.

 

In FY 2014, CDC and the Defense Threat Reduction Agency have jointly committed to accelerate progress on global health security by co-developing a strategy and devoting $40 million toward activities focusing on advancing the U.S. government’s GHS objectives in ten nations. The FY 2015 President’s Budget will include an increase of $45 million within CDC to prevent avoidable catastrophes, detect threats early, and mobilize effective responses to contain outbreaks. The increase also would allow CDC to partner with up to ten countries in 2015 to begin implementation and accelerate successful CDC efforts including training of field epidemiologists, developing new diagnostic tests, building capacities to detect new pathogens, building public health emergency management capacity, and supporting outbreak responses.

 

HHS, Department of State (DoS), US Department of Agriculture (USDA), and Department of Defense (DoD) will work closely with global partners to build countries’ global health security capacities in areas such as surveillance, detection and response in order to slow the spread of antimicrobial resistance, establish national biosecurity systems, reduce zoonotic disease transmission, increase routine immunization, establish and strengthen national infectious disease surveillance and laboratory systems, and develop public health electronic reporting systems and emergency operations centers.

 

Countries joining the United States to meet the Global Health Security goals at today’s launch were Argentina, Australia, Canada, Chile, China, Ethiopia, Finland, France, Georgia, Germany, India, Indonesia, Italy, Japan, Kazakhstan, Mexico, Netherlands, Norway, Republic of Korea, Russian Federation, Saudi Arabia, South Africa, Turkey, Uganda, United Kingdom, and, Vietnam.

3-D Changes in DNA May Lead to a Genetic Form of ALS

 

DNA contains a person’s genetic code, which is made up of a unique string of bases, chemicals represented by letters. Portions of this code are divided into genes that provide instructions for making molecules (proteins) that control how cells function. The normal C9orf72 gene contains a section of repeating letters; in most people, this sequence is repeated two to 25 times. In contrast, the mutation associated with amyotrophic lateral sclerosis (ALS, also known as Lou Gehrig’s disease), and frontotemporal degeneration (FTD), can result in up to tens of thousands of repeats of this section. In ALS, the muscle-activating neurons in the spinal cord die, eventually causing paralysis. In FTD neurons in particular brain areas die leading to progressive loss of cognitive abilities. The mutation may also be associated with other neurodegenerative diseases such as Alzheimer’s and Huntington’s diseases.

 

According to an article published online in Nature (5 March 2014), new findings reveal how a mutation, a change in the genetic code that causes neurodegeneration, alters the shape of DNA, making cells more vulnerable to stress and more likely to die. The particular mutation, in the C9orf72 gene, is the most common cause for ALS and for FTD, which is the second most common type of dementia in people under 65.

 

For those experiments, the authors used induced pluripotent stem cells (iPSC) containing the C9orf72 mutation that were derived from the skin of ALS patients. The iPSCs can be turned into different types of cells, in this case into motor neurons, which are the cells that die in patients with ALS. The iPSC technology lets researchers to study the direct effects of disease-causing human mutations on brain or spinal cord cells, using in vitro techniques.

 

Using sophisticated molecular techniques, the authors showed that the mutation causes changes in the three-dimensional shape of DNA. DNA is normally shaped like a twisted ladder, but repeating sequences can fold into G-quadruplexes, stacks of square-shaped molecules known as G-quartets. According to the authors, this structure has been described as a square building with each floor representing one G-quartet, normally two to four stories high.

 

The results also showed that C9orf72 mutated DNA has profound effects on how the genetic message is processed in the cell. RNA, short for ribonucleic acid, acts as an important intermediary in the process that converts genetic information from DNA into functional proteins. This happens in two stages:  conversion of the DNA code into RNA is called transcription. RNA then forms proteins during a process known as translation.

 

The investigators discovered that the mutated DNA forms DNA-RNA hybrid structures called R loops. Then they showed that G-quadruplexes and R-loops interfered with the transcription process. Cells taken from patients (containing the C9orf72 mutation) produced shorter transcription products (or transcripts) compared with control cells (without the mutation) taken from healthy volunteers. These short transcripts result in abnormal functioning of the cell and can lead to cell death. According to the authors, unfortunately, these alternative DNA arrangements impede normal processing, much like a car encountering a series of speed bumps or the occasional roadblock while traveling to its destination.

 

Findings also suggest that the C9orf72 mutation has an effect in the nucleolus, a cellular structure located within the nucleus (which contains the cell’s DNA) and the site where initial steps in protein assembly occur. The nucleolus also plays a key role in directing the cell’s response to stress. The key protein inside the nucleolus is nucleolin. The study found that binding of the short transcription products formed by the C9orf72 mutation to nucleolin has toxic effects on cells. The authors showed that in healthy cells without the mutation, nucleolin is present only in a certain area of the nucleus, but in cells obtained from ALS patients, nucleolin is scattered throughout the nucleus. The authors postulated that abnormal distribution of nucleolin causes cells to become stressed and more likely to die, which can result in the pathology associated with ALS and FTD.

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

 

FDA Approves Impavido to Treat Leishmaniasis

 

Orphan diseases, molecular diagnostics, and now tropical diseases are one of the new focuses of drug development.

 

The FDA has approved Impavido (miltefosine) to treat a tropical disease called leishmaniasis. Leishmaniasis is a disease caused by Leishmania, a parasite which is transmitted to humans through sand fly bites. The disease occurs primarily in people who live in the tropics and subtropics. Most U.S. patients acquire leishmaniasis overseas.

 

Impavido is an oral medicine approved to treat the three main types of leishmaniasis: visceral leishmaniasis (affects internal organs), cutaneous leishmaniasis (affects the skin) and mucosal leishmaniasis (affects the nose and throat). It is intended for patients 12 years of age and older. Impavido is the first FDA-approved drug to treat cutaneous or mucosal leishmaniasis.

 

The FDA granted Impavido fast track designation, priority review, and orphan product designation. These designations were granted because the drug demonstrated the potential to fill an unmet medical need in a serious disease or condition, the potential to be a significant improvement in safety or effectiveness in the treatment of a serious disease or condition, and is intended to treat a rare disease, respectively. With this approval, Impavido’s manufacturer, Paladin Therapeutics, is awarded a Tropical Disease Priority Review Voucher under a provision included in the Food and Drug Administration Amendments Act of 2007 that aims to encourage development of new drugs and biological products for the prevention and treatment of certain tropical diseases.

 

Impavido’s safety and efficacy were evaluated in four clinical trials. A total of 547 patients received Impavido and 183 patients received either a comparator drug or a placebo. Results from these trials demonstrated that Impavido is safe and effective in treating visceral, cutaneous and mucosal leishmaniasis.

 

The labeling for Impavido includes a boxed warning to alert patients and health care professionals that the drug can cause fetal harm and therefore should not be given to pregnant women. Health care professionals should advise women to use effective contraception during and for five months after Impavido therapy.

 

The most common side effects identified in clinical trials were nausea, vomiting, diarrhea, headache, decreased appetite, dizziness, abdominal pain, itching, drowsiness and elevated levels of liver enzymes (transaminases) and creatinine.

 

Paladin Therapeutics is based in Montreal, Canada.

Baked Spinach with Cheese and Poached Egg

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Ingredients

3 pounds fresh baby spinach
3 1/2 to 4 1/2 Tablespoons extra virgin olive oil
Pinch Salt, pinch black pepper (optional)
1 1/2 Tablespoons almond flour
1 cup chicken stock or broth
3/4 cup grated Swiss cheese or 1/2 Tofutti (8 oz. container) soy cream cheese
2 Tablespoons Panko
1/4 teaspoon ground nutmeg

Directions 

1. Stem and wash the spinach, well, so all sand and grit is removed. Don’t dry.

2. Place spinach in a large pot over high heat. Cook, covered, with just the water clinging to leaves, stirring occasionally, until wilted, about 2 to 4 minutes for tendor baby spinach.

3. Transfer to a colander, immediately fill pot with cold water, transfer it back to the pot of cold water to shock it (stop the cooking) and drain again. Squeeze a small amount of the spinach, at a time, in your hands to extract as much water as possible. 

4. Chop the spinach coarsely. You should have about 3 cups of chopped spinach, or about 1 cup per pound. It’s amazing how, what seems like a lot of spinach (3 lbs.) cooks down so fast, to only 3 cups.  I figured on a 1 cup serving per person, or 1 pound store-bought spinach, per person.

5. Wipe out pot then add 2 Tablespoons olive oil over moderately high heat and stir in the spinach. Cook for 2 to 3 minutes or until all of the moisture from the spinach has boiled off –  you’ll know you’re done, just when the spinach begins to stick to the pan.

6. Lower the heat and sprinkle with almond flour and stir for 2 minutes to cook the flour.

7. Add 2/3 of your chicken stock or canned broth, a bit at a time, scraping up any stuck spinach as you do. Once the liquid is added, simmer for another minute or two, stirring frequently to prevent sticking. If needed, add all or part of remaining liquid. Season with pinch salt and pepper. (both optional)

8. Preheat oven to 375 degrees. Lightly oil a 1-2-quart baking dish.

9. Stir 1/2 cup Swiss cheese (or Tofutti or consider substituting with Fontina or Taleggio) into the spinach and pour it into the baking dish. 

10. Mix the remaining cheese with Panko crumbs and sprinkle on spinach.

11. Add 1 1/2 Tablespoons remaining olive oil and pour it over the top. Bake until heated through and slightly brown on the top, about 30 minutes. While it’s baking, make 1 poached egg per person. Keep the yolk loose and not hard-boiled. On top of each serving of spinach, add one intact poached egg. Be sure not to break it.

 

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Because, we’re trying to cut way down on animal protein, I experiment with veggie recipes a lot. The above photo represents the first attempt, which was delicious, but the shredded cheese on top was a bit too crisp. It did occur to me that a small child, might like the idea of eating a beautiful egg in a nest of healthy spinach and little twigs of shredded cheese. For this reason, I left this photo in.

 

To get me to eat cereal, when I was a tot, my mother used to make something over the stove, called Wheatena, which she served with warm milk and raisins.  She called it tiger cereal.  The tigers were the raisins.  And, to this day, as you see, I remembered.  Kids love to play games, no matter what they’re doing.  I think today’s tots would love, egg in spinach nest idea, eating the “twigs“ one at a time, etc.  However, this tasty recipe will definitely appeal to adults as well.

 

The photo at the top of the page, represents the third try, where I decided that single servings with an egg (poached, fried, or soft-boiled) on each, was the best and most attractive way to serve this spinach/egg dish.

 

In the first try, I used grated Swiss cheese and soft boiled eggs. Second try I used Tofutti, grated Taleggio and poached eggs. Third, but not last try, I used grated soy mozzarella and fried eggs with trimmed egg whites. The flavor of all three is delicious. I would opt to serve this recipe in individual dishes, like the top photo, no matter what cheese or egg is used.

 

It’s clear that this recipe is highly versatile because it can be served for breakfast, lunch or dinner and excellent for brunch. Imagine ten of the pretty little dishes (top photo), served at your next brunch.

 

Not only would a toddler love this recipe, but we adults love it too. For people who are put off by eggs, consider another healthy option, of making scrambled eggs, with a tablespoon served on top of each spinach portion.

 

Bon Appetit!