Innovation and Barriers to Change – The Convergence of Healthcare, Business and Clinical Research

 

After reading the third book by Clayton Christensen, this one on “Innovator’s Prescription, A Disruptive Solution for Health Care,“ a clear picture has appeared about the challenges and barriers when new ideas, products, processes etc. surface and face resistance to adoption. While we as an industry focus on the clinical research space, challenges to innovation in our business are no different than challenges in any business. As a result, we wrote an article reflecting on the barriers to change when technology solutions replace paper-based operations. We decided to use analogous situations in business, biology and healthcare to complete the picture. Here is an excerpt and the complete article is found on our website.

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What a person hears he/she may doubt
What he/she sees, he/she may possibly doubt
But what he/she does, cannot be doubted
(Adapted from Seaman Knapp: American Agriculturist and Educator)

 

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                           Before                                  After

 

Some of us may be curious and adventuresome, while some of us are not; and that is okay. Some say “if it ain’t broke why fix it” and put off decisions until a crisis hits. While some crises are predictable and others seem to happen by chance, unfortunately, crises can be catastrophic and lethal, or at a minimum, require energy and resources to reverse. Crises can occur both in medicine and in business and the similarities are stark. In medicine, for example, some diseases are silent like hypertension and high cholesterol, and their consequences may not appear for 20 years or more. Other diseases are the result of self-inflicted “wounds” caused by “bad behavior” such as smoking, and these crises may also not appear for 20 years or more. Finally, there are chronic diseases, like hemophilia, that must be actively managed, or symptoms rapidly appear with potentially dire consequences. Likewise in business, crises can arise both within and outside of a company, and can be unpredictable as well as self-inflicted.

 

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

Vanessa Hays, Editorial Contributor

Test Your Knowledge of Vitamin D

 

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Calcium regulation in the human body. The role of vitamin D is shown in orange

 

Vitamin D is a nutrient found in some foods that is needed for health and to maintain strong bones. It does so by helping the body absorb 1) ___ (one of bone’s main building blocks) from food and supplements. People who get too little vitamin D may develop soft, thin, and brittle bones, a condition known as rickets in children and osteomalacia in adults. Vitamin D is important to the body in many other ways as well. Muscles need it to move, for example, nerves need it to carry messages between the 2) ___ and every body part, and the immune system needs vitamin D to fight off invading bacteria and viruses. Together with calcium, vitamin D also helps protect older adults from osteoporosis. Vitamin D is found in cells throughout the body.

 

The amount of vitamin D you need each day depends on your 3) ___. Average daily recommended amounts from the Food and Nutrition Board (a national group of experts) for different ages are listed below in International Units (IU). Very few foods naturally have vitamin D. Fortified foods provide most of the vitamin D in American diets.

 

1. Fatty fish such as salmon, tuna, and mackerel are among the best sources.

2. Beef liver, cheese, and egg yolks provide small amounts.

3. Mushrooms provide some vitamin D. In some mushrooms that are newly available in stores, the vitamin D content is being boosted by exposing these mushrooms to ultraviolet light.

4. Almost all of the U.S. milk supply is fortified with 400 IU of vitamin D per quart. But foods made from milk, like cheese and ice cream, are usually not fortified.

5. Vitamin D is added to many breakfast cereals and to some brands of orange juice, yogurt, margarine, and soy beverages; check the labels.

 

The body makes vitamin D when skin is directly exposed to the sun, and most people meet at least some of their vitamin D needs this way. Skin exposed to 4) ___ indoors through a window will not produce vitamin D. Cloudy days, shade, and having dark-colored skin also cut down on the amount of vitamin D the skin makes. Despite the importance of the sun to vitamin D synthesis, it is prudent to limit exposure of skin to sunlight in order to lower the risk for skin cancer. When out in the sun for more than a few minutes, wear protective clothing and apply sunscreen with an SPF (sun protection factor) of 8 or more. Tanning beds also cause the skin to make vitamin D, but pose similar risks for skin cancer. People who avoid the sun or who cover their bodies with sunscreen or clothing should include good sources of vitamin D in their diets or take a supplement. Recommended intakes of vitamin D are set on the assumption of little sun exposure.

 

Vitamin D is found in supplements (and fortified foods) in two different forms: D2 (ergocalciferol) and D3 (cholecalciferol). Both increase vitamin D in the blood.

 

Because vitamin D can come from sun, food, and supplements, the best measure of one’s vitamin D status is 5) ___ levels of a form known as 25-hydroxyvitamin D. Levels are described in either nanomoles per liter (nmol/L) or nanograms per milliliter (ng/mL), where 1 nmol/L = 0.4 ng/mL. In general, levels below 30 nmol/L (12 ng/mL) are too low for bone or overall health, and levels above 125 nmol/L (50 ng/mL) are probably too high. Levels of 50 nmol/L or above (20 ng/mL or above) are sufficient for most people. By these measures, some Americans are vitamin D deficient and almost no one has levels that are too 6) ___. In general, young people have higher blood levels of 25-hydroxyvitamin D than older people and males have higher levels than females. By race, non-Hispanic blacks tend to have the lowest levels and non-Hispanic whites the highest. The majority of Americans have blood levels lower than 75 nmol/L (30 ng/mL).

 

Certain other groups may not get enough vitamin D:

 

1. Breastfed infants, since human milk is a poor source of the nutrient. Breastfed infants should be given a supplement of 400 IU of vitamin D each day.

2. Older adults, since their skin doesn’t make vitamin D when exposed to sunlight as efficiently as when they were young, and their 7) ___ are less able to convert vitamin D to its active form.

3. People with dark skin, because their skin has less ability to produce vitamin D from the sun.

4. People with disorders such as Crohn’s disease or celiac disease who don’t handle fat properly, because vitamin D needs fat to be absorbed.

5. Obese people, because their body fat binds to some vitamin D and prevents it from getting into the blood.

 

People can become deficient in vitamin D because they don’t consume enough or absorb enough from food, their exposure to sunlight is limited, or their kidneys cannot convert vitamin D to its active form in the body. In children, vitamin D deficiency causes rickets, where the bones become soft and bend. It’s a rare disease but still occurs, especially among African American infants and children. In adults, vitamin D deficiency leads to osteomalacia, causing bone pain and 8) ___ weakness.

 

Vitamin D is being studied for its possible connections to several diseases and medical problems, including diabetes, hypertension, and autoimmune conditions such as multiple sclerosis. Two of them discussed below are bone disorders and some types of cancer.

 

As they get older, millions of people (mostly women, but men too) develop, or are at risk of, osteoporosis, where bones become fragile and may fracture if one falls. It is one consequence of not getting enough calcium and vitamin D over the long term. Supplements of both vitamin D3 (at 700–800 IU/day) and calcium (500–1,200 mg/day) have been shown to reduce the risk of bone loss and fractures in elderly people aged 62–85 years. Men and women should talk with their health care providers about their needs for vitamin D (and calcium) as part of an overall plan to prevent or treat osteoporosis. Some studies suggest that vitamin D may protect against colon 9) ___ and perhaps even cancers of the prostate and breast. But higher levels of vitamin D in the blood have also been linked to higher rates of pancreatic cancer. At this time, it’s too early to say whether low vitamin D status increases cancer risk and whether higher levels protect or even increase risk in some people. When vitamin D amounts in the blood become too high, it can become harmful. Signs of toxicity include nausea, vomiting, poor appetite, constipation, weakness, and weight loss. And by raising blood levels of calcium, too much vitamin D can cause confusion, disorientation, and problems with heart rhythm. Excess vitamin D can also damage the kidneys.

 

The safe upper limit for vitamin D is 1,000 to 1,500 IU/day for infants, 2,500 to 3,000 IU/day for children 1-8 years, and 4,000 IU/day for children 9 years and older, adults, and pregnant and lactating teens and women. Vitamin D toxicity almost always occurs from overuse of supplements. Excessive sun exposure doesn’t cause vitamin D poisoning because the body limits the amount of this vitamin it produces. Like most dietary supplements, vitamin D may interact or interfere with other medicines or supplements you might be taking. Here are several examples:

 

1. Prednisone and other corticosteroid medicines to reduce 10) ___ impair how the body handles vitamin D, which leads to lower calcium absorption and loss of bone over time.

2. Both the weight-loss drug orlistat (brand names Xenical® and Alli®) and the cholesterol-lowering drug cholestyramine (brand names Questran®, LoCholest®, and Prevalite®) can reduce the absorption of vitamin D and other fat-soluble vitamins (A, E, and K).

3. Both phenobarbital and phenytoin (brand name Dilantin®), used to prevent and control epileptic seizures, increase the breakdown of vitamin D and reduce calcium absorption.

 

ANSWERS: 1) calcium; 2) brain; 3) age; 4) sunshine: 5) blood; 6) high; 7) kidneys; 8) muscle; 9) cancer; 10) inflammation

Franklin Delano Roosevelt (1933-1945)

 

Franklin D. Roosevelt, the 32nd president of the United States, was elected to an unprecedented third term in 1940. It was during the end of this term that FDR’s health began to decline. The strain of leading the country through World War II had begun to take its toll. Exhausted from a summit in Teheran with Winston Churchill and Josef Stalin at the end of 1943, FDR’s health began to deteriorate rapidly after his return. Months passed and the President did not bounce back. He lost weight, his face thinned, and he suffered shortness of breath. At first, FDR’s personal physician, Vice Admiral Ross T. McIntire diagnosed the President’s problem as the “flu” and bronchitis.

 

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Franklin D. Roosevelt, the 32nd President of the United States

 

Not satisfied with the diagnosis, FDR’s family wanted a second opinion. Dr. McIntire arranged to have the President examined at Bethesda naval Hospital in March 1944 by Dr. Howard G. Bruenn. Dr. Bruenn, a cardiologist, found that FDR was suffering from hypertension, heart disease, left ventricular cardiac failure, and bronchitis. He recommended that FDR be given digitalis, put on a diet, and have bed rest. No one told the President of his serious condition, and he never asked.

 

FDR decided to run for a fourth term in 1944. No one made a serious attempt to persuade the President not to run or inform him of his health problems. While those who saw the President were shocked at his appearance, FDR’s spokesmen assured them that there was nothing to be concerned about. Less than a month before the election, Dr. McIntire claimed that FDR’s health was “perfectly OK.” FDR was re-elected in 1944, and soon thereafter attended a summit in Yalta with Churchill and Stalin. It was a strenuous trip for the ailing FDR, but he appeared to be alert.

 

Few Americans were ever aware of FDR’s disability. This was due in large part to the cooperation of members of the press, who almost always photographed him from the waist up. FDR insisted on this policy when he re-entered politics after his bout with polio, and it was continued during his presidency. When he ran for a fourth term in 1944, FDR chose Senator Harry Truman of Missouri as his Vice President. Their lunch gave the two men a chance to meet and discuss the presidential campaign. Truman was deeply concerned about FDR’s unhealthy appearance.

 

FDR’s blood pressure during 1944 reached dangerously high levels. In the wake of the President’s examination at Bethesda Naval Hospital in March of that year, FDR’s blood pressure was monitored closely. One of Dr. Bruenn’s 1944 recommendations for FDR’s health was bed rest. FDR was supposed to take brief naps during the day and get 10 hours of sleep each night. When Dr. Bruenn recommended this regimen FDR’s physician, Dr. McIntire, replied “You can’t do that. He’s the President of the United States.”

 

As the result of polio, FDR could neither stand nor walk without leg braces. When he did walk, FDR had to be supported by another person, usually one of his sons. When he reported to Congress on the Yalta conference on 1 March 1945, FDR made what was perhaps his only public reference to his braces. Apologizing for sitting down during his address, FDR stated that he was carrying around 10 pounds of steel.

 

Americans did not realize that they had re-elected a dying president. Dr. McIntire was selected as Roosevelt’s personal physician at the recommendation of Dr. Cary D. Grayson, who had been President Woodrow Wilson’s personal doctor. An eye, ear, nose, and throat specialist, Dr. McIntire appeared to have been chosen because FDR suffered from chronic sinus trouble. Shortly after FDR’s death, Dr. McIntire wrote (contrary to fact) that FDR’s blood pressure and heart signs had been normal. Dr. McIntire has been accused by historians of destroying FDR’s medical records to hide his misdiagnosis and mismanagement of the President’s case.

 

To escape the pressure of Washington, FDR often vacationed at the “Little White House”, a cottage in Warm Springs, Georgia. FDR went to the cottage on 29 March 1945 for a brief stay. The next day the President, while working at his desk, complained of a “terrific pain” in the back of his head. The pain was a stroke. FDR died at 3:35 p.m. Adapted from http://www.healthmedialab.com/html/president/roosevelt.html

Elevated Serum Pesticide Levels and Risk for Alzheimer Disease

 

The causes of late-onset Alzheimer disease (AD) are not yet understood but likely include a combination of genetic, environmental, and lifestyle factors. Limited epidemiological studies suggest that occupational pesticide exposures are associated with AD. Previously, it has been reported that serum levels of dichlorodiphenyldichloroethylene (DDE), the metabolite of the pesticide dichlorodiphenyltrichloroethane (DDT), were elevated in a small number of patients with AD (n=20). As a result, a study published online in JAMA Neurology (27 January 2014) was performed to evaluate the association between serum levels of DDE and AD and whether the apolipoprotein E (APOE) genotype modifies the association. This was a case-control study consisting of existing samples from patients with AD and control participants from the Emory University Alzheimer’s Disease Research Center and the University of Texas Southwestern Medical School’s Alzheimer’s Disease Center. For the study, there were 79 control and 86 AD cases and the following was measured or each subject: serum DDE levels, AD diagnosis, severity of AD measured by the Mini-Mental State Examination score, and interaction with APOE4 status. Results showed that levels of DDE were 3.8-fold higher in the serum of those with AD (2.64 ng/mg cholesterol) when compared with control participants (0.69 ng/mg cholesterol; P < .001). The highest tertile of DDE levels was associated with an odds ratio of 4.18 for increased risk for AD (P<.001) and lower Mini-Mental State Examination scores (−1.605; range; P <0.0001). The Mini-Mental State Examination scores in the highest tertile of DDE were −1.753 points lower in the subpopulation carrying an APOE e4 allele compared with those carrying an APOE e3 allele (P interaction = 0.04). Serum levels of DDE were also highly correlated with brain levels of DDE (p = 0.95). Exposure of human neuroblastoma cells to DDT or DDE increased levels of amyloid precursor protein. According to the authors, elevated serum DDE levels are associated with an increased risk for AD and carriers of an APOE4 e4 allele may be more susceptible to the effects of DDE, and that both DDT and DDE increase amyloid precursor protein levels, providing mechanistic plausibility for the association of DDE exposure with AD. The authors added that identifying people who have elevated levels of DDE and carry an APOE e4 allele may lead to early identification of some cases of AD.

Genetic Disorder Causing Strokes and Vascular Inflammation in Children

 

According to an article published online in the New England Journal of Medicine (19 February 2014), gene variants have been identified by NIH researchers that cause a rare syndrome of sporadic fevers, skin rashes and recurring strokes, beginning early in childhood. The discovery coincides with findings by an Israeli research group that identified an overlapping set of variants of the same gene in patients with a similar type of blood vessel inflammation.

 

The NIH research team first encountered a patient with the syndrome approximately 10 years ago. The patient, then 3 years old, experienced fevers, skin rash and strokes that left her severely disabled. Because there was no history of a similar illness in the family, the NIH group did not at first suspect a genetic cause, and treated the patient with immunosuppressive medication. However, when the team evaluated a second patient with similar symptoms two years ago — a child who had experienced recurrent fevers and six strokes by her sixth birthday — they began to suspect a common genetic cause and embarked on a medical odyssey that has led not only to a diagnosis, but to fundamental new insights into blood vessel disease.

 

In the report, the authors describe how next-generation genome sequencing, only recently available, facilitated a molecular diagnosis for patients in the study showing that harmful variants in the CECR1 gene were able to impede production of a protein vital to the integrity of healthy blood vessel walls. The authors showed that faulty variants in their patients’ DNA that encode the CECR1 gene cause a loss of function of the gene’s ability to produce of an enzyme called adenosine deaminase 2 (ADA2). Without it, abnormalities and inflammation in blood vessel walls result. The authors called the new syndrome, deficiency of ADA2, or DADA2. The enzyme ADA2 is chemically similar to the enzyme ADA1, whose deficiency results in severe combined immunodeficiency disease.

 

Whole-exome sequencing determines the order of DNA bases for the 1% of the human genome that codes for proteins. For the study, the authors methodically analyzed two of the patients’ exomes as well as exomes of their parents. Among hundreds of variants that distinguished each patient from their parents, the authors located two variants that are novel or rare in the CECR1 gene, which encodes ADA2. These variants were passed from both parents to the affected child. The whole-exome sequence of a third patient identified another harmful variant of CECR1 in addition to a small genomic deletion that shuts down the second copy of the gene. The authors needed only a sequence reading of that single gene to confirm that three other patients were affected by harmful variants in this gene and that three of the eight detrimental variants that eliminate the protein ADA2 were shared among the first six patients.

 

The team subsequently sequenced the CECR1 gene in three additional patients from Turkey who had some of the symptoms of the new syndrome. They found that a homozygous pair — a double dose of a different variant — from the one detected in the first six patients causes a disease called polyarteritis nodosa (PAN). PAN is a form of vasculitis, an inflammation of medium and small arteries that leads to pain, rashes, numbness, weakness and vital organ damage. PAN can cause kidney failure, heart attack and stroke.

 

The Israeli researchers, whose study is published concurrently in the journal, found the same mutation in CECR1 as those NIH patients with PAN. The patients in the Israeli study are from families that emigrated to Israel from the country of Georgia. According to the authors, this is the first time a single gene has been discovered that is involved in causing a system-wide form of vasculitis. The authors also found data from a study of adult patients showing that those who carry only one mutation in this gene may have a predisposition to develop adult onset stroke. They also induced ADA2 deficiency in a zebrafish animal model. They found that zebrafish embryos that produce less ADA2 than normal embryos have cerebral bleeds, similar to those seen in some of the children with ADA2 deficiency. The primary role for ADA2 protein is as a growth factor.  Data from the zebrafish model suggest that this growth factor plays a role in blood vessel development.

 

The discovery of the molecular basis of DADA2 has treatment implications. As an alternative to high doses of steroids, which produce profound side effects, the study suggests that treatment may include specialized drugs that inhibit inflammatory proteins produced during the syndrome. Also, since ADA2 is made in the bone marrow and circulates in the blood stream, the team is evaluating a way to replace ADA2 that is missing in the bloodstreams of those affected by DADA2. The authors have obtained approval from the Food and Drug Administration to test the safety and efficacy of using freshly frozen plasma to restore ADA2 functionality for treated patients. Alternatively, an artificial form of the protein would help, but is not currently in development. Bone marrow transplantation or genetic manipulation of bone marrow could also have a role in the treatment of these patients.

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

 

Target Health is also very active in the area of orphan diseases and recently had 2 face-to-face meetings with FDA discussing orphan disease development plans.

 

Rare Diseases in Children Pose Unique Challenges

 

The following was excepted from FDA Voice (Posted on February 27, 2014) and authored by Gayatri R. Rao, M.D., J.D., Director of FDA’s Office of Orphan Products Development.

 

Rare diseases – those that affect fewer than 200,000 people in the United States but collectively affect 30 million Americans – are often chronic, progressive, debilitating, and life-threatening. Because most are genetic in origin, they disproportionately affect children. The FDA is strongly committed to advancing safe and effective therapies for these young patients and in recognition of International Rare Disease Day on February 28, 2014, the following shows how FDA is focusing on pediatric rare diseases.

 

While developing products for any rare disease poses challenges, in part because of the small patient populations, developing products for children raises unique considerations. Historically, pediatric care has involved the use of off-label therapies that are unstudied or under-studied in children. For example, pediatric drug dosing often involved adjusting adult doses based on a child’s decreased weight, without considering potential age-based differences in drug metabolism and toxicities. Similarly, many medical devices used in children have been adapted – in homes, clinics, and operating rooms – to solve problems quickly, with little time to consider the long term consequences of a device’s effect on a growing child’s physiology and development. And while incentives currently exist to promote the development of products for pediatric rare diseases, development in this area continues to lag due to the compounded challenges associated with studying both a rare and pediatric population.

 

In recognition of these challenges, Congress directed FDA to issue a report and strategic plan focused on accelerating and encouraging the development of therapies for pediatric rare diseases. In response, FDA convened a series of public meetings from January 6 – 8, 2014 to discuss the many challenges in developing treatments for rare diseases, specifically for children with rare diseases, and how to overcome those challenges. These meetings generated a great deal of interest in the rare disease and pediatric communities. Hundreds of people attended either in person or via webcast and represented a wide swath of these overlapping communities, including patients, academicians, researchers, clinicians, industry, and governmental agencies, many of whom were noted experts in their respective fields. There were frank, robust and productive conversations on a wide range of topics. A few common themes emerged, especially the important role that patient advocacy groups, including parents of pediatric patients, play in furthering drug development, such as participating in the development of robust patient registries and natural history studies, and providing their perspectives on the risks and benefits of specific treatments. Another common theme was the need for strong collaborations between patients, researchers, industry, and government.

 

The Office of Orphan Products Development (OOPD), is now coordinating a cross-agency effort with Center for Drugs Evaluation and Research (CDER), the Center for Biologics Evaluation and Research (CBER), the Center for Devices and Radiological Health (CDRH), and the Office of Pediatric Therapeutics (OPT) to develop a report and strategic plan to encourage and accelerate the development of therapies for pediatric rare diseases. The goal of this report is to incorporate the valuable insights gained from these public meetings to inform and tailor ongoing and future agency initiatives to more effectively advance the development of such therapies. OOPD, in collaboration with CDER, is also launching a web-based educational tool for rare disease patients, advocacy groups, researchers and industry on various FDA-related topics. Current topics include the essentials of interacting with FDA and expanded access to products under development. The goal is to continue to add to this educational resource over time. For the new educational tool, as well as additional information, visit the OOPD Educational Resources web page. In addition, FDA and the National Institutes of Health (NIH) will jointly celebrate Rare Disease Day with a one-day program at NIH Masur Auditorium highlighting various rare diseases programs, research activities, and initiatives. For more information about this event that is free and open to the public, and available via webcast, visit the OOPD web page.

 

The needs of rare disease patients and the pediatric population are complex and pose challenging issues. We are committed to working with the pediatric rare disease community to face those challenges head-on and to accelerate the development safe and effective therapies for these diseases.

Stuffed Dates with Blood Oranges & Mandarins

 

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©Joyce Hays, Target Health Inc.

 

We just got back from a 10 day cruise in the Caribbean, where we allowed ourselves decadent desserts on a daily basis. Now, back in Manhattan, the idea of delicious fresh fruit, had great appeal, so here is what I came up with for dessert this weekend, for the two of us to get back onto a healthier track. It’s healthy delicious and if you want to impress guests with a colorful presentation, here is one dessert to consider. Oh, and btw, it’s quick and easy to prepare.

 

Ingredients

1.  4 mandarin or Clementine oranges

2.  2 blood oranges

3.  splash of Cointreau or orange blossom water

4.  8 ripe Medjool dates

5.  8 teaspoons mascarpone

6.  30 roasted/salted pistachios, shelled and coarsely chopped seeds from 1/2 pomegranate

 

Directions

Prep mandarins and blood oranges by slicing a small piece of the top and bottom off the unpeeled fruit. Now, with a sharp knife, slowly cut away strips of peel and pith.  Once the peel is removed, slice the citrus horizontally into nice pinwheels. You can use a mandolin, carefully or a sharp knife. Scatter the citrus rounds onto a plate. Add a light splash of Cointreau or orange blossom water to the citrus – It’s amazing how the Cointreau or orange blossom water enhances the natural perfume of the fresh citrus slices. I bought my orange blossom water and pistachios from Amazon.com.

 

Cut each date with a slice large enough to remove and discard the pits. Carefully stuff each date cavity with 1 teaspoon mascarpone. Press some chopped pistachio and pomegranate seeds onto the mascarpone. Scatter the remaining pistachio and pomegranate onto the plate. I bought pomegranate arils from FreshDirect.com, which is so much easier than prying each seed from a pomegranate.

 

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Here’s the orange blossom water, I used.

©Joyce Hays, Target Health Inc.

 

 

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This was a dessert plate for two. ©Joyce Hays, Target Health Inc.

 

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Jules and I tried this delicious fresh fruit in three ways: 1) without any additions  2) with about ½ teaspoon Cointreau on each orange slice. 3) with about 1/2 teaspoon orange blossom water (non-alcoholic) on each slice. I liked all three versions. Jules didn’t like the orange blossom water, but did like the other two versions, with a preference for the Cointreau.

 

Coffee and tea goes well with this dessert.  If you want to serve an alcoholic beverage and you’re using Cointreau on the orange slices, you might as well stick to the same in glasses, or consider a grappa.

 

Bon Appetit!