Conference: eSource Data in Clinical Investigations – May 2-3, 2017 – Doubletree Center City, Philadelphia, Pa
Target Health Inc. is pleased to announce that Dr. Jules Mitchel will be presenting at CBI’s 4th Annual Bootcamp on eSource Data in Clinical Investigations. The conference aims to initiate meaningful dialogues around early successes, failures and pain points through collaborative sessions and investigative case studies so that you can build an eSource adoption business case for senior leadership addressing balance of risk and cost.
Dr. Mitchel’s presentation is entitled: “The Future is Now: How to Obtain Stakeholder Buy-in and Initiate the Migration to eSource.” In this case study, you will learn how eSource reduced monitoring and increased overall data quality, as well as how to convince stakeholders to invest in eSource. You will also learn of the current challenges of interoperability between EHR and eSource and what the long-term strategy looks like in moving away from EDC as we know it today.
Please Mention Promo Code: NCE547 for a $500 discount when you register at the conference www.cbinet.com/esource.
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 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 Editor in Chief of On Target
Jules Mitchel, Editor
Effects of Aging
A map showing median age figures around the world. Credit: Joeyramoney at English Wikipedia – Transferred from en.wikipedia to Commons by Dryke using CommonsHelper., Public Domain, Wikipedia Commons
In humans, ageing represents the accumulation of changes in a human being over time, encompassing physical, psychological and social changes. Reaction time, for example, may slow with age, while knowledge of world events and wisdom may expand. Ageing is among the greatest known risk factors for most human 1) ___: of the roughly 150,000 people who die each day across the globe, about two thirds die from age-related causes.
The causes of ageing are uncertain; current theories are assigned to the damage concept, whereby the accumulation of damage (such as DNA oxidation) may cause biological systems to fail, or to the programmed ageing concept, whereby internal processes (such as DNA methylation) may cause ageing. Programmed ageing should not be confused with programmed cell death (apoptosis). The discovery, in 1934, that calorie restriction can extend lifespan by 50% in rats has motivated research into the delaying and prevention of ageing. On the other hand, very low-weight older people combating a disease, appear to have less resistance if they are too 2) ___.
In the 21st century, one of the most significant population trends is ageing. Currently, over 11% of the world’s current population are people aged 60 and older and the United Nations Population Fund (UNFPA) estimates that by 2050 that number will rise to approximately 22%. Greater longevity has occurred, world-wide, due to better nutrition, sanitation, health care, education and economic well-being. Consequently, fertility rates have continued to decline and life expectancy have 3) ___. Life expectancy at birth is over 80 now in 33 countries. Ageing is a “global phenomenon,” that is occurring fastest in developing countries, including those with large youth populations, and poses social and economic challenges to the work which can be overcome with “the right set of policies to equip individuals, families and societies to address these challenges and to reap its benefits.” As life expectancy rises and birth rates decline in developed countries, the median age rises accordingly. According to the United Nations, this process is taking place in nearly every country in the world. A rising median age can have significant social and economic implications, as the workforce gets progressively older and the number of old workers and retirees grows relative to the number of young workers. Older people generally incur more health-related costs than do younger people in the workplace and can also cost more in worker’s compensation and pension liabilities. In most developed countries an older workforce is somewhat inevitable. In the United States for instance, the Bureau of Labor Statistics estimates that one in four American workers will be 55 or older by 2020.
Changes With Ageing
The brain and nervous system are the body’s central control center. They control your body’s: movements, senses, thoughts and memories. They also help control the organs such as your heart and bowels. 4) ___ are the pathways that carry signals to and from your brain and the rest of your body. The spinal cord nerves run from your brain down the center of your back; extending out from the spinal cord to every part of the body. As humans age, the brain and nervous system go through natural changes, losing nerve cells and weight (atrophy). Nerve cells may begin to pass messages more slowly than in the past. Waste products can collect in the brain tissue as nerve cells break down. This can cause abnormal changes in the brain called plaques and tangles to form. A fatty brown pigment (lipofuscin) can also build up in nerve tissue. Breakdown of nerves can affect the senses; like reduced or lost reflexes or sensation, which can lead to problems with movement and balance. Slowing of thought, memory, and thinking is a normal part of aging. These changes are not the same in everyone. Some people have many changes in their nerves and brain tissue. Others have few changes. These changes are not always related to the effects on the ability to think.
Vital signs include body temperature, heart rate (pulse), breathing rate, and blood pressure. With ageing, vital signs may change, depending on the health of the individual. Normal body temperature does not change much with aging, however, it becomes harder for the body to control temperature. A decrease in the amount of fat below the skin makes it harder to stay 5) ___. Aging decreases the ability to sweat, hence, there may be difficulty sensing when the body becomes overheated. This puts older people at high risk of overheating (heat stroke) and also at risk for dangerous drops in body temperature. Fever is an important sign of illness in older people. It is often the only symptom for several days of an illness. A fever is also a sign of infection. When an older person has an infection, their body may not be able to produce a higher temperature. For this reason, it is important to check other vital signs, as well as any symptoms and signs of infection. With ageing, the pulse rate is about the same as before; however with exercise, it may take longer for the pulse to increase and longer for it to slow down afterward. One’s highest heart rate with exercise is also lower than it was when younger. Breathing rate usually does not change with 6) ___. But lung function decreases slightly. Healthy older people can usually breathe without effort.
Older people may become dizzy when standing up too quickly. This is due to a sudden drop in blood pressure. This kind of drop in blood pressure when standing is called orthostatic hypotension. Risk of having high blood pressure, or hypertension, increases with age. Other heart-related problems common in older adults include: very slow pulse or very fast pulse. heart rhythm problems such as atrial fibrillation. Medicines that are used to treat health problems in older people can affect the vital signs. For example, the medicine digitalis used for heart failure and blood pressure medicines called beta blockers may cause the pulse to slow. Diuretics (water pills) can cause low blood pressure, especially when changing body position too quickly.
Dementia and severe memory loss are not a normal part of aging. They can be caused by brain diseases such as Alzheimer disease, which doctors believe is associated with plaques and tangles forming in the brain and the buildup of lipofuscin. Delirium is sudden confusion that leads to changes in thinking and behavior. It is often due to illnesses that are not related to the brain. Infection can cause an older person to become severely confused. Certain medicines can also cause this. Thinking and behavior problems can also be caused by poorly controlled diabetes. Rising and falling blood sugar levels can interfere with thought. Mental and physical exercise can help your brain stay sharp. Physical exercise promotes blood flow to your brain. It also helps reduce loss of brain 7) ___. Some changes in the heart and blood vessels normally occur with age, but many other changes that are common with aging are due to modifiable factors that, if not treated, can lead to heart disease.
Watch this video about: Blood flow
The heart has a natural pacemaker system that controls the heartbeat. Some of the pathways of this system may develop fibrous tissue and fat deposits. The natural pacemaker (the SA node) loses some of its cells. These changes may result in a slightly slower heart rate. A slight increase in the size of the heart, especially the left ventricle, is not uncommon. The heart wall thickens, so the amount of blood that the chamber can hold may actually decrease despite the increased overall heart size. The heart may fill more slowly. Heart changes cause the ECG of a normal, healthy older person to be slightly different than the ECG of a healthy younger adult. Abnormal rhythms (arrhythmias), such as atrial fibrillation, are more common in older people. They may be caused by heart disease. Normal changes in the heart include deposits of the “aging pigment,” lipofuscin. The heart muscle cells degenerate slightly. The valves inside the heart, which control the direction of blood flow, thicken and become stiffer. A heart murmur caused by valve stiffness is fairly common in the elderly. Receptors, in blood vessels, called baroreceptors monitor the blood pressure and make changes to help maintain a fairly constant blood pressure when a person changes positions or is doing other activities. The baroreceptors become less sensitive with aging. This may explain why many older people have orthostatic hypotension, a condition in which the blood pressure falls when a person goes from lying or sitting to standing. This causes dizziness because there is less blood flow to the brain. The capillary walls thicken slightly. This may cause a slightly slower rate of exchange of nutrients and wastes. The main artery from the heart (aorta) becomes thicker, stiffer, and less flexible. This is probably related to changes in the connective tissue of the blood vessel wall. This makes the blood pressure higher and makes the heart work harder, which may lead to thickening of the heart muscle (hypertrophy). The other arteries also thicken and stiffen. In general, most elderly people have a moderate increase in blood pressure. Normally, the heart continues to pump enough 8) ___ to supply all parts of the body. However, an older heart may not be able to pump blood as well when you make it work harder.
All vital organs begin to lose some function, with aging, during adulthood. Aging changes occur in all of the body’s cells, tissues, and organs, and these changes affect the functioning of all body systems. Living tissue is made up of cells. There are many different types of cells, but all have the same basic structure. Tissues are layers of similar cells that perform a specific function. The different kinds of tissues group together to form organs. Nerve tissue is made up of nerve cells (neurons) and is used to carry messages to and from various parts of the body. The brain, spinal cord, and peripheral nerves are made of nerve tissue.
Watch this video about: Nerve conduction
Cells are the basic building blocks of tissues. All cells experience changes with aging. They become larger and are less able to divide and multiply. Among other changes, there is an increase in pigments and fatty substances inside the cell (lipids). Many cells lose their ability to function, or they begin to function abnormally.
As aging continues, waste products build up in tissue. A fatty brown pigment called lipofuscin, collects in many tissues, as do other fatty substances. Connective tissue changes, becoming more stiff. This makes the organs, blood vessels, and airways more rigid. Cell membranes change, so many tissues have more trouble getting oxygen and nutrients, and removing carbon dioxide and wastes. Many tissues lose mass. This process is called atrophy. Some tissues become lumpy (nodular) or more rigid. Because of cell and tissue changes, organs also change with aging. Aging organs slowly lose function. Most people do not notice this loss immediately, because you it’s rare to use organs to their fullest ability. Organs have a reserve ability to function beyond the usual needs. For example, the heart of a 20-year-old is capable of pumping about 10 times the amount of blood that is actually needed to keep the body alive. After age 30, an average of 1% of this reserve is lost each year. The biggest changes in organ reserve occur in the heart, lungs, and kidneys. The amount of reserve lost varies between people and between different organs in a single person. These changes appear slowly and over a long period. When an organ is worked harder than usual, it may not be able to increase function. Sudden heart failure or other problems can develop when the body is worked harder than usual. Things that produce an extra workload (body stressors) include the following:
- Significant life changes
- Sudden increased physical demands on the body, such as a change in activity or exposure to a higher altitude, which could result in altitude sickness.
Loss of reserve also makes it harder to restore balance (equilibrium) in the body. Drugs are removed from the body at a slower rate. Lower doses of medications may be needed, and side effects become more common. Medication side effects can mimic the symptoms of many diseases, so it is easy to mistake a 9) ___ reaction for an illness. Some medications have entirely different side effects in the elderly than in younger people. No one knows how and why people change as they get older. Some theories claim that aging is caused by injuries from ultraviolet light over time, wear and tear on the body, or byproducts of metabolism. Other theories view aging as a predetermined process controlled by genes. No single process can explain all the changes of aging. Aging is a complex process that varies as to how it affects different people and even different organs.
A gerontologist does scientific studies of the biological, psychological, and sociological phenomena associated with old age and aging. Most 10) ___ feel that aging is due to the interaction of many lifelong influences. These influences include heredity, environment, culture, diet, exercise and leisure, past illnesses, and many other factors. Unlike the changes of adolescence, which are predictable to within a few years, each person ages at a unique rate. Some systems begin aging as early as age 30. Other aging processes are not common until much later in life. Although some changes always occur with aging, they occur at different rates and to different extents. There is no way to predict exactly how you will age.
ANSWERS: 1) diseases; 2) thin; 3) risen; 4) Nerves; 5) warm; 6) age; 7) cells; 8) blood; 9) drug; 10) gerontologists
The hand of an older man. Source: Wikipedia Commons
Gerontology, from the Greek, geron, “old man” and -logia, “study of”; coined by Ilya Ilyich Mechnikov (in 1903) is the study of the social, cultural, psychological, cognitive, and biological aspects of aging. It is distinguished from geriatrics, which is the branch of medicine that specializes in the treatment of existing disease in older adults. Gerontologists include researchers and practitioners in the fields of biology, nursing, medicine, criminology, dentistry, social work, physical and occupational therapy, psychology, psychiatry, sociology, economics, political science, architecture, geography, pharmacy, public health, housing, and anthropology.
Gerontology encompasses the following:
- studying physical, mental, and social changes in people as they age
- investigating the biological aging process itself including aging’s causes, effects and mechanisms (biogerontology)
- investigating the social and psycho-social impacts of aging (sociogerontology)
- investigating the psychological effects on aging (psychogerontology)
- investigating the interface of biological aging with aging-related diseases (geroscience)
- investigating the effects of an ageing population on society (demography)
- exploring the relationship between the aging and their environment (environmental gerontology)
- applying this knowledge to policies and programs, including the macroscopic (for example, government planning) and microscopic (for example, running a nursing home) perspectives.
The multidisciplinary nature of gerontology means that there are a number of sub-fields, as well as associated fields such as physiology, anthropology, social work, public health, psychology and sociology that overlap with gerontology. One of the world’s oldest drugs which was first mentioned by Hippocrates in the 5th Century BCE could help restore memory in Alzheimer’s patients, scientists hope. Salsalate, which comes from the same family as aspirin, was typically used to treat inflammatory conditions like rheumatoid arthritis. But a new study suggests that it can prevent the build-up of toxic proteins in the brain and even reverse damage already done, unblocking pathways and restoring memory.
In the medieval world, several physicians wrote on issues related to Gerontology. Avicenna’s The Canon of Medicine (1025) offered instruction for the care of the aged, including diet and remedies for problems including constipation. He also wrote on the aches and conditions of the elderly. His scholarly work covers sleep disorders, forgetfulness, how to strengthen memory, and causes of mortality. Ishaq ibn Hunayn (died 910) wrote works on the treatments for forgetfulness (U.S. National Library of Medicine, 1994).
While the number of aged humans, and life expectancy, tended to increase in every century since the 14th, society tended to consider caring for an elderly relative as a family issue. It was not until the coming of the Industrial Revolution that ideas shifted in favor of a societal care-system. Some early pioneers, such as Michel Eugene Chevreul, who himself lived to be 102, believed that aging itself should be a science to be studied. Elie Metchnikoff coined the term “gerontology” c. 1903. However, it was not until the 1940s that pioneers like James Birren began organizing gerontology into its own field. Recognizing that there were experts in many fields all dealing with the older population, it became apparent that a group like the Gerontological Society of America (founded in 1945) was needed. Two decades later, James Birren was appointed as the founding director of the first academic research center devoted exclusively to the study of aging, the Ethel Percy Andrus Gerontology Center. The Baltimore Longitudinal Studies of Aging began in 1958 in order to study physiological changes in healthy middle-aged and older men living in the community by testing them every two years on numerous physiological parameters. In 1967, the University of South Florida and the University of North Texas (formerly North Texas State University) received Older Americans Act training grants from the U.S. Administration on Aging to launch the nation’s first degree programs in gerontology, at the master’s level. In 1975, the University of Southern California’s Leonard Davis School of Gerontology, became the country’s first school of gerontology within a university and, later, offered the first PhD in Gerontology degree. Gerontological Education has flourished in the United States since 1967 and degrees at all academic levels are now offered by a number of colleges and universities. One of the pioneering gerontologists, Robert Neil Butler, pushed for care and respect of the elderly. Several university-based centers on aging have been founded such as the Duke University Center on Aging, the University of Georgia Institute of Gerontology, the Center of Aging at the University of Chicago, and the Stanford Center on Longevity. Currently, PhD programs in gerontology are available at Miami University, the University of Kansas, University of Kentucky, University of Maryland Baltimore, University of Massachusetts Boston, and the University of Southern California.
The world is forecast to undergo rapid population aging in the next several decades. In 1900, there were 3.1 million people aged 65 years and older living in the United States. However, this population continued to grow throughout the 20th century and reached 31.2, 35, and 40.3 million people in 1990, 2000, and 2010, respectively. Notably, in the United States and across the world, the “baby boomer” generation began to turn 65 in 2011. Recently, the population aged 65 years and older has grown at a faster rate than the total population in the United States. The total population increased by 9.7%, from 281.4 million to 308.7 million, between 2000 and 2010. However, the population aged 65 years and older increased by 15.1% during the same period. It has been estimated that 25% of the population in the United States and Canada will be aged 65 years and older by 2025. Moreover, by 2050, it is predicted that, for the first time in United States history, the number of individuals aged 60 years and older will be greater than the number of children aged 0 to 14 years. Those aged 85 years and older (oldest-old) are projected to increase from 5.3 million to 21 million by 2050. Adults aged 85–89 years constituted the greatest segment of the oldest-old in 1990, 2000, and 2010. However, the largest percentage point increase among the oldest-old occurred in the 90- to 94-year-old age group, which increased from 25.0% in 1990 to 26.4% in 2010. With the rapid growth of the aging population, social work education and training specialized in older adults and practitioners interested in working with older adults are increasingly in demand.
Genetic theories of aging propose that aging is programmed within each individual’s genes. According to this theory, genes dictate cellular longevity. Programmed cell death, or apoptosis, is determined by a “biological clock” via genetic information in the nucleus of the cell. Genes responsible for apoptosis provide an explanation for cell death, but are less applicable to death of an entire organism. An increase in cellular apoptosis may correlate to aging, but is not a ‘cause of death’. Environmental factors and genetic mutations can influence gene expression and accelerate aging. More recently epigenetics have been explored as a contributing factor. The epigenetic clock, which objectively measures the biological age of cells and tissues, may become useful for testing different biological aging theories. General imbalance theories of aging suggest that body systems, such as the endocrine, nervous, and immune systems, gradually decline and ultimately fail to function. The rate of failure varies system by system. Accumulation theories of aging suggest that aging is bodily decline that results from an accumulation of elements. Elements can be foreign and introduced to the body from the environment. Other elements can be the natural result of cell metabolism. An example of an accumulation theory is the Free Radical Theory of Aging. According to this theory, byproducts of regular cell metabolism called free radicals interact with cellular components such as the cell membrane and DNA and cause irreversible damage.
The idea that free radicals are toxic agents was first proposed by Rebeca Gerschman and colleagues. In 1956, Denham Harman proposed the free-radical theory of aging and even demonstrated that free radical reactions contribute to the degradation of biological systems. Oxidative damage of many types accumulate with age, such as oxidative stress that oxygen-free radicals, because the free radical theory of aging argues that aging results from the damage generated by reactive oxygen species (ROS). ROS are small, highly reactive, oxygen-containing molecules that can damage a complex of cellular components such as fat, proteins, or from DNA, they are naturally generated in small amounts during the body’s metabolic reactions. These conditions become more common as we age, including diseases related to aging, such as dementia, cancer and heart disease.
DNA damage has been one of the many causes in diseases related to aging. The stability of the genome is defined by the cells machinery of repair, damage tolerance, and checkpoint pathways that counteracts DNA damage. One hypothesis proposed by Gioacchino Failla in 1958 is that damage accumulation to the DNA causes aging. The hypothesis was developed soon by physicist Leo Szilard. This theory has changed over the years as new research has discovered new types of DNA damage and mutations, and several theories of aging argue that DNA damage with or without mutations causes aging.
To demonstrate how far the interest in longevity goes, Google has a separate division called Calico to study this aspect of aging.
What is Alphabet? Alphabet is mostly a collection of companies. The largest of which, of course, is Google. This newer Google is a bit slimmed down, with the companies that are pretty far afield of our main internet products contained in Alphabet instead. What do we mean by far afield? Good examples are our health efforts: Life Sciences (that works on the glucose-sensing contact lens), and Calico focused on longevity. Fundamentally, we believe this allows us more management scale, as we can run things independently that aren’t very related. What could be better? No wonder we are excited to get to work with everyone in the Alphabet family. Don’t worry, we’re still getting used to the name too!
Urinary Biomarker That May Help Track ALS
Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease in which motor neurons, cells that control muscle activity such as walking, talking and breathing, gradually die off, resulting in paralysis. There is no cure for ALS.
A study in Neurology (22 February 2017) suggests that analyzing levels of the protein p75ECD in urine samples from people with ALS) may help monitor disease progression as well as determine the effectiveness of therapies. The authors discovered that levels of urinary p75 ECD increased gradually in patients with ALS as their disease progressed over a 2-year study period. The study was supported by National Institute of Neurological Disorders and Stroke (NINDS) and National Center for Advancing Translational Sciences (NCATS), both part of the National Institutes of Health.
Analysis of the samples from 54 patients revealed that those who began the study with lower levels of urinary p75ECD survived longer than did patients who had higher levels of the protein initially, suggesting that it could be a prognostic marker of the disease and may inform patients about their illness. The authors noted that this may be useful in selecting participants for clinical trials and in improving study design. The protein p75 is important early in life, but does not appear in adults unless motor neurons are injured. Previous studies in mouse models of ALS reported that p75 was re-expressed in motor neurons as the animals became sick and p75ECD was found in the urine of the mice even before they exhibited muscle weakness. p75 has also been seen on motor neurons in post-mortem tissue from ALS patients.
According to the authors, more research is needed to validate the use of urinary p75ECD as a biomarker of ALS and to further investigate the role of the protein in the disease.
Docosahexaenoic Acid and Bronchopulmonary Dysplasia in Preterm Infants
Sometimes a study does not work.
Studies in animals and in humans have suggested that docosahexaenoic acid (DHA), an n−3 long-chain polyunsaturated fatty acid, might reduce the risk of bronchopulmonary dysplasia, but appropriately designed trials are lacking.
As a result, a study published in the New England Journal of Medicine (2017;376:1245-1255) randomly assigned 1273 infants born before 29 weeks of gestation and within 3 days after their first enteral feeding to receive either an enteral emulsion providing DHA at a dose of 60 mg per kilogram of body weight per day or a control (soy) emulsion without DHA until 36 weeks of postmenstrual age. Treatment was stratified according to gender, gestational age <27 weeks or 27 to <29 weeks, and center). The primary outcome was bronchopulmonary dysplasia, defined on a physiological basis (with the use of oxygen-saturation monitoring in selected infants), at 36 weeks of postmenstrual age or discharge home, whichever occurred first.
Results showed that a total of 1205 infants survived to the primary outcome assessment. Of the 592 infants assigned to the DHA group, 291 (49.1% by multiple imputation) were classified as having physiological bronchopulmonary dysplasia, as compared with 269 (43.9%) of the 613 infants assigned to the control group (relative risk adjusted for randomization strata, 1.13; P=0.02). The composite outcome of physiological bronchopulmonary dysplasia or death before 36 weeks of postmenstrual age occurred in 52.3% of the infants in the DHA group and in 46.4% of the infants in the control group (adjusted relative risk, 1.11; P=0.045). There were no significant differences between the two groups in the rates of death or any other neonatal illnesses. Bronchopulmonary dysplasia based on a clinical definition occurred in 53.2% of the infants in the DHA group and in 49.7% of the infants in the control group (P=0.06).
According to the authors, enteral DHA supplementation at a dose of 60 mg per kilogram per day did not result in a lower risk of physiological bronchopulmonary dysplasia than a control emulsion among preterm infants born before 29 weeks of gestation; In fact, it may have resulted in a greater risk.
First Drug Approved for Primary Progressive MS
On March 28, the FDA approved Ocrevus (ocrelizumab) to treat adult patients with relapsing forms of multiple sclerosis (MS) and primary progressive multiple sclerosis (PPMS). This is the first drug approved by the FDA for primary progressive multiple sclerosis (PPMS). The FDA granted this application breakthrough therapy designation, fast track designation, and priority review.
MS is a chronic, inflammatory, autoimmune disease of the central nervous system that disrupts communication between the brain and other parts of the body. It is among the most common causes of neurological disability in young adults and occurs more frequently in women than men. For most people with MS, episodes of worsening function (relapses) are initially followed by recovery periods (remissions). Over time, recovery may be incomplete, leading to progressive decline in function and increased disability. Most people experience their first symptoms of MS between the ages of 20 and 40. PPMS is characterized by steadily worsening function from the onset of symptoms, often without early relapses or remissions. The U.S. Centers for Disease Control and Prevention estimates that approximately 15% of patients with MS have PPMS.
The efficacy of Ocrevus for the treatment of relapsing forms of MS was shown in two clinical trials in 1,656 participants treated for 96 weeks. Both studies compared Ocrevus to another MS drug, Rebif (interferon beta-1a). In both studies, the patients receiving Ocrevus had reduced relapse rates and reduced worsening of disability compared to Rebif. In a study of PPMS in 732 participants treated for at least 120 weeks, those receiving Ocrevus showed a longer time to the worsening of disability compared to placebo.
Ocrevus is an intravenous infusion given by a health care professional. Ocrevus should not be used in patients with hepatitis B infection or a history of life-threatening infusion-related reactions to Ocrevus. Ocrevus must be dispensed with a patient Medication Guide that describes important information about the drug’s uses and risks. Ocrevus can cause infusion-related reactions, which can be serious. These reactions include, but are not limited to, itchy skin, rash, hives, skin redness, flushing, low blood pressure, fever, tiredness, dizziness, headache, throat irritation, shortness of breath, swelling of the throat, nausea, and fast heartbeat. Additionally, Ocrevus may increase the risk for malignancies, particularly breast cancer. Delay Ocrevus treatment for patients with active infections. Vaccination with live or live attenuated vaccines is not recommended in patients receiving Ocrevus.
In addition to the infusion-related reactions, the most common side effect of Ocrevus seen in the clinical trials for relapsing forms of MS was upper respiratory tract infection. The most common side effects in the study of PPMS were upper respiratory tract infection, skin infection, and lower respiratory tract infection.
The FDA granted approval of Ocrevus to Genentech, Inc.
Sherry Mushroom Tart with Goat Cheese, Tofutti, & Leeks
Jules likes the crust, but I think it could be much better; however, the rest of this pie is wonderful. If you buy your pie dough, this is an easy recipe and if your aim is a meatless meal, you’ll be happy with this. You could also make this your veggie with fish, seafood and/or poultry; and a brunch treat over the weekend. ©Joyce Hays, Target Health Inc.
You could serve this Sherry Mushroom Tart as an appetizer with chilled wine. As you can imagine, we’ve eaten a lot, as the tart evolved, so tried different white wines. The best were Sauvignon Blanc, Pouilly Fuisse, Pouilly Fume, Pino Grigio, Champagne and Prosecco. I’m not crazy about Chardonnay, but if you like it, go for it, it would be perfect.
- 3 Tablespoons olive oil
- 2 Tablespoons cream sherry for cooking leeks
- 2 Tablespoons cream sherry for cooking mushrooms
- 1 red onion
- 2 scallions, sliced very finely
- 2 eggs, beaten
- 3 pounds’ leeks, white parts and 1 inch of pale green parts, thinly sliced
- 20 fresh garlic cloves, sliced
- 2 teaspoons fresh thyme leaves, well chopped
- 1 bay leaf
- 1/2 cup chicken stock or broth
- Pinch salt
- Pinch black pepper
- Pinch chili flakes
- 1 teaspoon curry powder
- 1 container Tofutti
- 3 ounces’ soft goat cheese, crumbled
- 1 pound mixed mushrooms, such as oyster, chanterelle and cremini, brushed clean and coarsely chopped
- Almond (or chickpea) flour for dusting (when you roll dough out)
- Tofutti dough (made at home, or your own pie crust recipe, or bought at store)
Get all ingredients together in the same place. ©Joyce Hays, Target Health Inc.
- First, make your favorite pie dough or buy at store and refrigerate overnight.
I’m not yet anywhere near, a good crust maker, but here’s the latest experiment, making the pie dough, using Tofutti. ©Joyce Hays, Target Health Inc.
- Chop, cut, slice everything.
Chopping onion, scallions, garlic, leeks all at the same time. ©Joyce Hays, Target Health Inc.
- In a skillet, over medium-high heat, add the olive oil.
- Add the garlic, sliced leeks, chopped onion, scallions and sauté until translucent, 4 to 5 minutes.
- Add the thyme, bay leaf, chicken stock, 2 Tablespoons cream sherry, all seasoning and spices.
This photo is steps 3, 4, and 5. ©Joyce Hays, Target Health Inc.
- Reduce the heat to low, cover and simmer until the leeks are nearly tender, about 15 minutes. Uncover and cook, stirring occasionally and being careful not to let the leeks brown, until almost all the liquid has evaporated, about 15 minutes more.
- Remove and discard the bay leaf. Transfer everything in the skillet to a bowl. Stir in the container of Tofutti, goat cheese, and mix everything together, very well. Set aside
- In another fry pan, over medium-high heat, add olive oil 2 Tablespoons cream sherry and add the chopped mushrooms, and sauté until the mushrooms are soft and have released their juices, 3 to 4 minutes. Set aside
Cooking mushrooms with sherry. ©Joyce Hays, Target Health Inc.
- Now, take dough out of fridge and roll it out into a large circle, so it will fit onto your oiled pie dish.
Scatter flour on parchment paper or on your counter, to roll out the dough. ©Joyce Hays, Target Health Inc.
Fit the dough to your pie dish. On the right, there’s an extra piece of dough that I pushed onto an empty space. ©Joyce Hays, Target Health Inc.
Crust baked and coming out of oven to get the filling poured in. ©Joyce Hays, Target Health Inc.
- Preheat an oven to 400°F.
- Transfer the dough to pie dish. Don’t worry if it doesn’t fit exactly. Push it, pinch it until it’s in place. If you have little pieces of extra dough, just pinch/push them into place on your pie dish.
- Bake your crust according to your own recipe or go by the directions on the package, if you bought it. Bake it slightly, then remove from oven.
- Add and mix the 2 beaten eggs to the bowl of leeks, stir them in to combine well.
- Now, add the mixture in the bowl of leeks, to the sherry mushrooms in the skillet. If you forgot to add the goat cheese and any spice or herb, do it now and mix to combine well.
Mixing everything together, before spooning this, into the pie crust. ©Joyce Hays, Target Health Inc.
- Next, spread all the leek/goat cheese mixture to within 1 inch of the edge of the dough. Bake until the crust puffs and
- both the crust and the leeks are golden, about 15 to 20 minutes.
The filling has been spooned into the pie shell and about to go into the oven. ©Joyce Hays, Target Health Inc.
- Five minutes, before tart is done, open the oven and sprinkle finely chopped parsley and scallions over the top and bake for 5 minutes more.
- Remove from oven, and let the tart stand for 5 to 10 minutes. Cut into wedges and serve warm.
If a recipe turns out well, we’ll just eat that with some wine, and put away the rest of the meal. This was one of those times. :) ©Joyce Hays, Target Health Inc.
We had fried chicken thighs with this. ©Joyce Hays, Target Health Inc.
We had sautéed shrimp with this. ©Joyce Hays, Target Health Inc.
As long as they stay sweet and juicy, we’ll be having fresh mango for dessert. ©Joyce Hays, Target Health Inc.
This is one of our reliable standbys, well chilled, Louis Jadot, Pouilly-Fuisse, wonderful with the Mushroom Tart. ©Joyce Hays, Target Health Inc.
We’ve seen several plays, on and off Broadway, but would not recommend them. We’re looking forward to Arthur Millers, The Price and at The Metropolitan Opera, Beethoven’s Fidelio.
The geopolitical situation in the U.S. and around the world, is not good. In addition to reading voraciously about it, I’ve been listening to a lot of Chopin. Here are some favorite pieces to bring stress levels down:
Happy Spring Everyone !
From Our Table to Yours !